Daily Archives: October 28, 2021

PLYMOUTH MEETING, Pa., Oct. 27, 2021 /PRNewswire/ -- INOVIO (NASDAQ: INO) announced today that third quarter 2021 financial results will be released after the market close on November 9, 2021. Following the release, INOVIO will host a live conference call and webcast at 4:30 p.m. ET to discuss financial results and provide a general business update regarding its DNA Medicines Platform, including the company's global Phase 3 efficacy trial (INNOVATE) involving its COVID-19 vaccine candidate, INO-4800.

A live and archived version of the audio presentation will be available online at http://ir.inovio.com/events-and-presentations/default.aspx. This is a listen-only event but will include a live Q&A with analysts.

About INOVIO

INOVIO is a biotechnology company focused on rapidly bringing to market precisely designed DNA medicines to treat and protect people from infectious diseases, cancer, and diseases associated with HPV. INOVIO is the first company to have clinically demonstrated that a DNA medicine can be delivered directly into cells in the body via a proprietary smart device to produce a robust and tolerable immune response. Specifically, INOVIO's lead therapeutic candidate VGX-3100 met primary and secondary endpoints for all evaluable subjects in REVEAL 1, the first of two, Phase 3 trials for precancerous cervical dysplasia, demonstrating ability to destroy and clear both high-grade cervical lesions and the underlying high-risk HPV-16/18. INOVIO is also evaluating INO-4800, a DNA vaccine candidate against COVID-19, in a Phase 2/3 clinical trial; the Phase 3 segment of which has received regulatory approvals to begin in Colombia, Mexico, Brazil and Philippines. INOVIO's partners, Advaccine Biopharmaceuticals and International Vaccine Institute, are also evaluating INO-4800 in ongoing clinical trials in China and South Korea, respectively.

Partners and collaborators include Advaccine, ApolloBio Corporation, AstraZeneca, The Bill & Melinda Gates Foundation, Coalition for Epidemic Preparedness Innovations, Defense Advanced Research Projects Agency/Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense/Department of Defense, HIV Vaccines Trial Network, International Vaccine Institute, Kaneka Eurogentec, Medical CBRN Defense Consortium, National Cancer Institute, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Ology Bioservices, the Parker Institute for Cancer Immunotherapy, Plumbline Life Sciences, Regeneron, Richter-Helm BioLogics, Thermo Fisher Scientific, University of Pennsylvania, Walter Reed Army Institute of Research, and The Wistar Institute. For more information, visit http://www.inovio.com.

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CONTACTS:Media: Jeff Richardson, 267-440-4211, jrichardson@inovio.comInvestors: Ben Matone, 484-362-0076, ben.matone@inovio.com

This press release contains certain forward-looking statements relating to our business, including our plans to develop and commercialize DNA medicines, our expectations regarding our research and development programs, including the planned initiation and conduct of pre-clinical studies and clinical trials and the availability and timing of data from those studies and trials, and our ability to successfully manufacture and produce large quantities of our product candidates if they receive regulatory approval. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials, product development programs and commercialization activities and outcomes, our ability to secure sufficient manufacturing capacity to mass produce our product candidates, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines, our ability to support our pipeline of DNA medicine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2020 , our Quarterly Report on Form 10-Q for the quarter ended June 30, 2021 and other filings we make from time to time with the Securities and Exchange Commission. There can be no assurance that any product candidate in our pipeline will be successfully developed, manufactured, or commercialized, that results of clinical trials will be supportive of regulatory approvals required to market products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and we undertake no obligation to update or revise these statements, except as may be required by law.

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INOVIO to Report Third Quarter 2021 Financial Results on November 9, 2021 - Yahoo Finance

PALM BEACH, Fla., Oct. 26, 2021 /PRNewswire/ --FinancialNewsMedia.com News Commentary- The global psychedelic drugs market remains at an early stage in its life cycle, with most companies currently developing their go-to-market strategy. The market players of psychedelics are involved in the clinical trials of several psychedelic drugs to address mental health, which continues to present significant unmet need.For the behavioral health industry, psychedelics present an opportunity to potentially bolster providers' treatment toolbox and help patients for whom current psychiatric medications have failed. While it's unclear exactly what the future of psychedelics in the U.S. behavioral health industry will look like, Canadians are looking at a clearer picture. When it comes to psychedelic wellness, Canada is leading the way, accordingto Behavioral Health Business. They said: Regulations were recently relaxed there to make it easier for alternative medicine companies to develop psychedelic behavioral health treatments.Those newfound flexibilities are similar to right-to-try laws in the US, which allow terminally ill patients to use experimental therapies that have passed Phase I in the U.S. Food and Drug Administration's approval process.The difference, however, is that only one state in the US along with several municipalities has authorized exemptions for psilocybin; meanwhile, all 13 Canadian provinces and territories currently have exemptions for the psychedelic substance often used as a source for alternative behavioral health treatments." Active Companies active today in markets include: Cybin Inc. (NYSE: CYBN) (NEO: CYBN), COMPASS Pathways plc (NASDAQ: CMPS), Mind Medicine (MindMed) Inc. (NASDAQ: MNMD), Eli Lilly and Company (NYSE: LLY), Johnson & Johnson (NYSE: JNJ).

Under the care of a clinician, patients using psilocybin for behavioral health treatment typically receive the psychedelic drug to treat conditions like stress, anxiety and depression, especially for patients who have not had success using other treatments or are facing terminal illnesses. As with the US, possession of psilocybin mushrooms in Canada is illegal. However, last August, Health Canada the country's regulatory health body approved the use of psilocybin to treat four terminally ill patients for anxiety, stress and depression.Several months later, in December,Health Canada also approved exemptions to a group of doctors and therapiststo use psilocybin for research purposes, allowing them to study its effects on patients in hopes of developing therapies for future use. As a result, British Columbia which is also home to a number of Canadian cannabis companies has become a hotbed for psychedelic wellness startups.

Cybin Inc. (NYSE AMERICAN: CYBN) (NEO: CYBN) BREAKING NEWS: Cybin Announces FDA Investigational New Drug Authorization of Cybin's Sponsored Feasibility Study using Kernel Flow Technology - Cybin Inc. ("Cybin" or the "Company"), a biotechnology company focused on progressing psychedelic therapeutics, today announced that the U.S. Food and Drug Administration ("FDA") has authorized an Investigational New Drug ("IND") application to proceed with the Company's sponsored feasibility study using Kernel's Flow technology to measure ketamine's psychedelic effect on cerebral cortex hemodynamics.

"The word psychedelic means 'mind-manifesting,' but what has been missing is useful 'mind-imaging'the ability to dynamically trace the neural correlates of human conscious experience. Conventional neuroimaging just isn't dynamic enough to study the psychedelic experience in the brain as it happens. This study of ketamine's psychedelic effects while wearing headgear equipped with sensors to record brain activity could open up new frontiers of understanding," said Dr. Alex Belser, Cybin's Chief Clinical Officer.

Leveraging Kernel's quantitative neuroimaging technology ("Kernel Flow") may lead to new frontiers in psychedelic therapeutics by enabling the acquisition of longitudinal brain activity before, during and after a psychedelic experience, providing quantification of what was previously subjective patient reporting.

"Quantitatively measuring the brain within the context of a psychedelic experience is a promising frontier," said Bryan Johnson, founder and Chief Executive Officer of Kernel. "With Kernel Flow, Cybin's researchers can start putting numbers and quantification to subjective states of mind, including altered ones."

Kernel Flow uses pulsed light instead of continuous wave light to increase measured brain information. In contrast with electroencephalography ("EEG") electrodes that usually require gel on the head or functional magnetic resonance imaging ("fMRI") studies that require a participant to lie in a scanner, Kernel Flow is easily wearable. The entire system is the size and look of a bicycle helmet and could, in the future, be more broadly used for neuroscientific or physiological studies of brain activity during psychedelic use.

As part of Cybin's sponsorship of the feasibility study, the Company will retain an exclusive interest in any innovations that are discovered or developed through its independent analysis of the study findings. Kernel will hold the same rights relating to its Kernel technology. CONTINUEDRead the full Press Release for Cybin at: https://www.cybin.com/news

In other active company biotech news in the markets this week:

COMPASS Pathways plc (NASDAQ: CMPS), a mental health care company dedicated to accelerating patient access to evidence-based innovation in mental health, recently welcomed the topline data shared from an open-label study of psilocybin therapy for depression in cancer patients. Within one week of a single administration of COMP360 psilocybin therapy, 50% of participants achieved remission in depression symptoms, which was sustained for the eight week follow-up period.

This investigator-initiated feasibility study was conducted by Maryland Oncology Hematology at the Aquilino Cancer Center in Rockville, Maryland, USA. It was an open-label study involving 30 patients with cancer diagnosis and major depressive disorder (MDD), all of whom completed the study. Half of the participants had previously been treated for their current episode of depression with antidepressants and all were receiving active treatment for cancer; 19 participants had no previous experience with psychedelic substances. Patients were given a 25mg dose of COMP360 psilocybin in conjunction with psychological support from specially trained therapists, following the COMP360 psilocybin therapy protocol.

Mind Medicine (MindMed) Inc. (NASDAQ: MNMD), a leading biotech company developing psychedelic-inspired therapies, recently announced that Dr.Matthias Liechtipresented data from several ongoing studies at the INSIGHT Conference inBerlin, Germany. These investigator-initiated studies are being conducted as part of MindMed's ongoing collaboration with the UHB Liechti Lab.

"While both LSD and psilocybin have a long history in psychiatric research, psilocybin is being studied in a majority of ongoing clinical trials of psychedelics," said Dr. Liechti. "It is important for us to understand the acute effect characteristics of different psychedelics, and to understand how these substances interact with other treatments like antidepressants. We look forward to fully analyzing the exciting data produced by these studies and publishing our findings later this year."

Eli Lilly and Company (NYSE: LLY) recently announced the board of directors of Eli Lilly and Company (NYSE: LLY) has declared a dividend for the fourth quarter of 2021 of $0.85 per share on outstanding common stock.

The dividend is payable on December 10, 2021 to shareholders of record at the close of business on November 15, 2021.Lilly is a global health care leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism.

Johnson & Johnson (NYSE: JNJ) The Janssen Pharmaceutical Companies ofJohnson & Johnson(Janssen) previously announced the submission of a New Drug Application (NDA) to theU.S. Food and Drug Administration(FDA) for esketamine nasal spray. Janssen is seeking FDA approval of esketamine for treatment-resistant depression in adults.

Esketamine is an investigational, rapidly acting antidepressant that works differently than currently available therapies for major depressive disorder. Through glutamate receptor modulation, esketamine is thought to help restore connections between brain cells in people with treatment-resistant depression.

"Of the nearly 300 million people who suffer from major depressive disorder worldwide, about one-third do not respond to currently available treatments.3,4This represents a major unmet public health need," saidMathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC. "We are committed to working with the FDA to bring this new treatment option toU.S.patients with treatment-resistant depression and to the medical community."

DISCLAIMER: FN Media Group LLC (FNM), which owns and operates Financialnewsmedia.com and MarketNewsUpdates.com, is a third- party publisher and news dissemination service provider, which disseminates electronic information through multiple online media channels. FNM is NOT affiliated in any manner with any company mentioned herein. FNM and its affiliated companies are a news dissemination solutions provider and are NOT a registered broker/dealer/analyst/adviser, holds no investment licenses and may NOT sell, offer to sell or offer to buy any security. FNM's market updates, news alerts and corporate profiles are NOT a solicitation or recommendation to buy, sell or hold securities. The material in this release is intended to be strictly informational and is NEVER to be construed or interpreted as research material. All readers are strongly urged to perform research and due diligence on their own and consult a licensed financial professional before considering any level of investing in stocks. All material included herein is republished content and details which were previously disseminated by the companies mentioned in this release. FNM is not liable for any investment decisions by its readers or subscribers. Investors are cautioned that they may lose all or a portion of their investment when investing in stocks. For current services performed FNM was compensated twenty six hundred dollars for news coverage of current press release issued by Cybin Inc.by a non-affiliated third party. FNM HOLDS NO SHARES OF ANY COMPANY NAMED IN THIS RELEASE.

This release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E the Securities Exchange Act of 1934, as amended and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. "Forward-looking statements" describe future expectations, plans, results, or strategies and are generally preceded by words such as "may", "future", "plan" or "planned", "will" or "should", "expected," "anticipates", "draft", "eventually" or "projected". You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events, or results to differ materially from those projected in the forward-looking statements, including the risks that actual results may differ materially from those projected in the forward-looking statements as a result of various factors, and other risks identified in a company's annual report on Form 10-K or 10-KSB and other filings made by such company with the Securities and Exchange Commission. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this release are made as of the date hereof and FNM undertakes no obligation to update such statements.

Contact Information:Media Contact email: [emailprotected] +1(561)325-8757

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North America Continues Leading The Way In Psychedelic Wellness - PRNewswire

Introduction

SARS-Cov-2 is a novel coronavirus causing the severe acute respiratory syndrome spreading around the world since the end of 2019.1,2 It belongs to a family of single-stranded RNA viruses (+ssRNA), as the severe acute respiratory syndrome virus (SARS-CoV) and the Middle East respiratory syndrome virus (MERS-CoV). SARS-CoV-2 infection can cause mild to severe pneumonia and its mortality rate is higher in patients with comorbidities and older patients.3,4 Although different vaccines for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have been developed and are now available,5 there are no effective antiviral drugs to treat the disease, except for Remdesivir authorized by the United States Food and Drug Administration (US FDA) to counteract the emergency.6 mRNA-based vaccines were developed by Moderna and Pfizer/BioNTech,7,8 but there is still uncertainty about their efficacy (~95%), safety, and immunogenicity concerning SARS-CoV-2 spike glycoprotein (S protein). Similarly, viral vector vaccines were produced by Johnson and Johnson and by the University of Oxford/AstraZeneca, although the safety of AstraZenecas vaccine is currently under revision.9,10 Unfortunately, new strains of the virus have developed so far with new mutations and this could inhibit the effectiveness of vaccines, and delays the end of the pandemic.11 Given the high infectivity of new mutations in the virus and the slowness of vaccine programming, herd immunity will be difficult to achieve in a short time. It is very likely that new coronavirus diseases may still emerge in the future. Thus, it can be necessary to develop alternative therapies based on the use of natural compounds, as epigallocatechin-3-gallate (EGCG), with antiviral features, to circumvent SARS-CoV-2 infection. EGCG, is the principal constituent and most important polyphenolic catechin found in green tea.1218 As largely reported, EGCG possesses many biological properties (ie antioxidant, antitumor, anti-inflammatory) due to a galloyl side chain contained in its chemical structure.19 It has been shown that polyphenols and EGCG, through sticking with some molecules present in viruses, are able to regulate their functions. Specifically, EGCG by binding to the receptors present on the membrane of the host cells or directly to the viral surface inhibits the interaction between the host cells and the virus. As a result, EGCG represses the replication and the transcription of the virus, thus inactivating its activity.20,21 As recently detailed described by Wang et al,22 EGCG has inhibitory activities towards different viruses. Specifically, EGCG is able to suppress the replication, the transcription and the infection of DNA virus as Hepatitis B Virus (HBV),2327 Herpes Simplex Virus (HSV)2831 and Epstein-Barr Virus (EBV) through different molecular mechanisms.3235 Moreover, EGCG has similar effects on RNA virus as Human Immunodeficiency Virus (HIV),3742 Hepatitis C virus (HCV),4345 and Influenza A virus (IAV).4648 Additionally, in vitro studies demonstrated that EGCG is capable to inhibit the replication of some Enterovirus (CVB3, EV71) by regulating the oxidative stress of host cells.49,50 Similar effects were also detected in Arboviruses, particularly in Chikungunya virus (CHIKV).5155 Finally, several pre-clinical studies confirmed the antiviral activity of EGCG also against Coronaviruses, especially against SARS-Cov-2.5673 Basically, EGCG can inhibit the cell entry of these viruses or their replication and transcription, through different molecular mechanisms which are not completely known. In this review, we summarize these experimental pieces of evidence and highlighted the potential use of EGCG as an alternative therapeutic choice for alleviating or treat SARS-Cov-2 infection.

COVID-19 is caused by SARS-CoV-2 infection.56 The initial clinical manifestations of COVID-19 include respiratory symptoms, such as fever, fatigue and dry cough, are accompanied by atypical clinical manifestations such as sore throat, headache and diarrhea.57 Around one week later, patients exhibited difficulty breathing and hypoxia, during which the secretion of intracellular pro-inflammatory factors Interleukin-6 (IL-6), Interleukin-17 (IL-17) and tumor necrosis factor (TNF-)) increased significantly, and the total number of circulating lymphocytes decreased. Then, the symptoms rapidly deteriorated into acute respiratory distress syndrome (ARDS), sepsis, blood coagulation dysfunction and irreversible metabolic acidosis. Eventually, some severe cases would lead to death. Structurally, SARS-CoV-2 contains four proteins including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. During host cell entry, SARS-CoV-2 relies on its S proteins for binding to the host cell-surface receptor. The S protein binds to the host receptor through the receptor-binding domain (RBD) in the S1 subunit, followed by the fusion of the S2 subunit to the cell membrane. SARS-CoV-2 recognizes the cell membrane receptor angiotensin-converting enzyme 2 (ACE2) receptor to bind with the viral S protein, thus forming RBDACE2 complex, by which the virus is embedded into the host cell where it starts replication. Thus, if a substance can bind the S protein, or possesses a strong affinity to ACE2 receptor, which blocks the formation of RBDACE2 complex, it could suppress the viral entry into host cells. Regarding the antiviral effects of EGCG on SARS-CoV-2, different pre-clinical studies have been performed (Table 1). Basically, the inhibition effects of EGCG on SARS-CoV-2 replication occur through its actions on the ACE2 receptor, the main protease (Mpro, a 3C-like protease) and RNA-dependent RNA polymerase (RdRp) (Figure 1).

Table 1 A Summary of Pre-Clinical Studies on the Antiviral Activity of EGCG Against SARS-Cov-2

Figure 1 The inhibitory effects of EGCG on SARS-CoV-2 life cycle. The figure represents the inhibitory effects of EGCG on SARS-CoV-2 cycle. Basically, the inhibition effects of EGCG on SARS-CoV-2 replication occurs through its actions on the ACE2 receptor, the main protease (Mpro, a 3C-like protease) and RNA-dependent RNA polymerase (RdRp).

Abbreviations: EGCG, epigallocatechin-3-gallate; pp1a, nuclear protein phosphatase 1 ; pp1ab, 2-O-methyltransferase; Mpro, main protease; ACE2, angiotensin-converting enzyme 2; S-protein, spike protein; RdRp, RNA-dependent RNA polymerase.

Mhatre et al58 reviewed the antiviral activities of EGCG theaflavin-3,3-digallate (TF3) against positive-sense single-stranded RNA viruses, including SARS-CoV-2. The authors suggested that both the tea polyphenols are capable to interact with the receptors present in the structure of SARS-CoV-2 virus, thus inhibiting its replication. Particularly, the theaflavins (TFs), can be employed as prophylactic agents due to their capacity to bind Spike receptor-binding domain (RBD), the principal binding domain of the S protein located on the S1 subunit of SARS-CoV-2 virus. EGCG can be used as a potential prophylactic due to its ability to dock to various active sites of SARS-CoV-2 virus. The authors highlighted the needing of additional studies on the specificity, safety, and efficacy of these polyphenols, to confirm their use not only as a dietary supplement, but also as therapeutic agents for COVID-19 infections. Menegazzi et al,59 speculated that EGCG and others catechins (ie, GTE) supplementation could be effective in controlling the inflammation damages occurring in SARS-CoV-2 infection, through complex molecular mechanisms involving different interacting transcriptor factors (ie signal transducer and activator of transcription, STAT; nuclear factor kappa-light-chain-enhancer of activated B cells, NF-B; NF-E2related factor 2; Nuclear Factor Erythroid-Derived 2-Related Factor 2, Nrf2). Similarly, Mendonca et al,60 suggested that the combination of EGCG, thymoquinone (TQ), and vitamin D3 can activate Nrf2-dependent genes and preserve the cells against SARS-CoV-2 infection. Singh et al,61 studied the binding of polyphenols (ie, EGCG, TF1, TF2a, TF2b, hesperidin, quercetagetin, and myricetin) with SARS-CoV-2 RdRp and thus tested their potential to treat COVID-19. The authors demonstrated that EGCG, TF1, TF2a, TF2b, TF3, can bind (in highly stable manner) to the active site of RdRp. These four natural polyphenols can act as potential inhibitors for the SARS-CoV-2 RdRp, although additional studies will be necessary to validate their efficacy against SARS-CoV-2 infection. An in-silico analysis conducted by Sagaama et al,62 revealed that the succinic acid (SA), L-pyroglutamic acid (L-PGA), N-phenyl-thioacetamide (N-NPTA), 2-amino-5-chloropyridine hydrogen succinate (ACPS), epigallocatechine Gallate (EGCG) or, 2-oxoglutarate dehydrogenase E1 component putative (KDH) and, selenomethionine (SeM) compounds could represented potential antiviral candidates for treatment of COVID-19 based on B3LYP/6-311++G** calculations and molecular docking. Data emerged from this study suggest that the compounds ACPS and KDH are powerful species in the treatment of SARS-CoV-2 infections. A different study conducted by Jang et al,63 demonstrated that EGCG and theaflavins, inhibited activity against the SARS-CoV-2 3CL-protease, in HEK293T cells, in a dose-dependent manner and without signs of cytotoxicity for both compounds at any dose used. Sharma et al,64 performed an in-silico drug repurposing followed by molecular dynamics (MD) simulation and MM-GBSA calculation for targeting SARS-CoV-2 main protease (Mpro). Mpro was screened for already known FDA approved drugs and some natural compounds, including EGCG. Specifically, the authors proposed that EGCG, withaferin A, dolutegravir and artesunate could be considered potential drugs for COVID-19. A molecular docking studies was also conducted by Mhatre et al,65 to study the exact interaction of EGCG and TF3 with the putative binding sites of SARS-CoV-2. The in-silico results emerged from this study should promote the evaluation of the broad-spectrum antiviral activity of the tea polyphenols in the treatment of COVID-19. Similarly, Zhu et al66 performed in vitro studies by using of the Mpro of SARS-Cov-2 for docking simulation to screen flavan-3-ols and proanthocyanidins (Pas), to identify potential candidates for counteracting SARS-Cov-2 infection. Data emerged from docking simulation and in vitro assay, indicated that ()-catechin-3-O-gallate (CAG), ()-epicatechin-3-O-gallate (ECG), ()-gallocatechin-3-O-gallate GCG), EGCG, procyanidin A2 (PA2) and B2 (PB2) are able to inhibit the Mpro activity of SARS-Cov-2, thus can be used to interfere with SARS-Cov-2 infection. Wang et al,67 conducted in-depth and comprehensive bioinformatics analysis for the screening of therapeutic drugs and their related pathways in COVID-19 disease. Results indicated that trans-resveratrol, EGCG and BX795 possess multiple anti-viral effects. It is of note that coronaviruses encode for polyproteins that are cleaved by 3CL protease for maturation. Thus, 3CL protease could be considered the main target of antivirals against coronaviruses. Based on this concept, Chiou et al,68 conducted an in vitro study on the inhibitory effects of 1,2,3,4,6-pentagalloylglucose (PGG) and EGCG against the SARS-CoV-2- 3-chymotrypsin-like protease (3CLpro) protease. Data revealed that PGG and EGCG inhibited of viral protease activity of SARS-CoV-2 3CLpro, thus suggesting their potential application in the treatment of SARS-CoV-2 infection. Later on, in a fascinating study Du et al,69 screened and identified, by using multiple strategies (ie molecular docking, surface plasmon resonance, fluorescence resonance energy transfer (FRET)-based inhibition assay) different active ingredients of Traditional Chinese Medicine (TCM) with inhibitory effects against SARS-CoV-2 3CLpro, including EGCG. Results demonstrate that EGCG showed a higher affinity with SARS-CoV-2 3CLpro thus suggesting its potential in the treatment of COVID-19 disease. A fascinating in vitro study performed by Jang et al,70 demonstrated that EGCG can inhibit coronavirus replication. Specifically, the authors used low pathogenic human coronavirus HCoV-OC43 (beta coronavirus) and HCoV-229E (alpha coronavirus), as a coronavirus model system to dissect the effect of EGCG on coronavirus processing. Results demonstrated that EGCG treatment decreases viral RNA and viral protein production in the media suggesting that EGCG inhibits coronavirus replication. By using the molecular docking approach, Chourasia et al71 demonstrated that the catechins (mainly EGCG and ECG) inhibited papain-like protease protein (PLPro). Specifically, catechin bind to the S1 ubiquitin-binding site of PLPro, which restrain its protease function and abolish SARS-CoV-2 inhibitory function on ubiquitin proteasome system and interferon stimulated gene system. Considering EGGCs antiviral and anti-inflammatory properties, the authors concluded that these natural compounds could be considered as a putative therapeutic agent for SARS-CoV-2 infection. Finally, a recent research conducted by Henss et al,72 examined the antiviral activity of EGCG against SARS-CoV-2. EGCG arrested the entry of SARS-CoV-2, MERS and SARS-CoV pseudo typed lentiviral vectors and restrained virus infections in vitro. Moreover, an inhibition of the SARS-CoV-2 spikereceptor interaction was also detected. Altogether these finding highlighted the potential use of EGCG as an alternative therapeutic choice for the treatment of SARS-CoV-2 infection.

Here, we summarized recent findings on the potential role of EGCG in the treatment of SARS-CoV-2 infection. Accumulated pieces of evidence reported that EGCG has antiviral properties against different viruses, including SARS-Cov-2.22 Specifically, it has been proved that EGCG inhibits the enzymatic activity of the coronavirus 3CL protease, thus interfering with its replication. Moreover, EGCG can regulate specific target as the viral S protein and RdRp. EGCG is also capable of inhibiting the replication of coronaviruses in cell cultures. Results from molecular docking analyses demonstrated that EGCG prevents SARS-CoV-2 entry into the target cell through inhibition of RBD in viral membrane identifying with ACE2. Finally, EGCG can interfere with the viral start replication by suppressing Mpro activity, although all these effects should be confirmed in vivo. A set of experiments evaluated the in vivo distribution of EGCG in human bodies7479 and data showed that the values of EGCG concentration in the colon and intestine were higher than most of the concentrations necessary to promote 3CL protease required to effectively 3CL protease inhibition. More pre-clinical studies, clinical trials and epidemiological analysis will be extremely needed to validate EGCG anti-COVID-19 applications. EGCG and its stable lipophilic derivatives could also be potential prophylactic as well as therapeutic agents looking at their properties to dock at various active sites of SARS-CoV-2. Results from these studies will shed light on the role of the EGCG and the underlying molecular mechanisms for the treatment of SARS-CoV-2 infection. However, based on the current results published in the literature, it is not possible to say at all that EGCG can be considered as an election therapeutic drug for Covid-19. Due to the absence of specificity, EGCG could bind to other proteins present in the human body, thus provoking side-effects. EGGC may not be used in the treatment of COVID-19, but as a nutraceutical or dietary supplement, especially in the earlier stages of clinical manifestations of COVID-19. After extensive studies on EGGC and other similar polyphenols regarding their specificity, activity, bioavailability and safety, there can be considerations on their use in the treatment of viral infections including COVID-19.

We are grateful to Dr. Alessandra Trocino and Mrs. Cristina Romano from the National Cancer Institute of Naples for providing excellent bibliographic service and assistance. Sabrina Bimonte and Cira Antonietta Forte are co-first authors of this study. Marco Cascella and Arturo Cuomo are co-last authors of this study.

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval for the version to be published, and agree to be accountable for all aspects of the work.

The authors report no conflicts of interest in this work.

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6. Vitiello A, Ferrara F, Porta R. Remdesivir and COVID-19 infection, therapeutic benefits or unnecessary risks? Ir J Med Sci. 2021;12. doi:10.1007/s11845-020-02482-2

7. Baden LR, El Sahly HM, Essink B, et al.; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403416. doi:10.1056/NEJMoa2035389

8. Xia X. Domains and functions of spike protein in Sars-Cov-2 in the context of vaccine design. Viruses. 2021;13(1):109. doi:10.3390/v13010109

9. Bjrnstad-Tuveng TH, Rudjord A, Anker P. Fatal cerebral haemorrhage after COVID-19 vaccine. Tidsskr nor Laegeforen. 2021;141. English, Norwegian. doi:10.4045/tidsskr.21.0312

10. Maas DPMSM, Kramers C, Smit HJCA, Middeldorp S, Helsloot I. Prikpauze AstraZeneca proportioneel? [Temporary suspension of AstraZenecas vaccine; a reconstruction]. Ned Tijdschr Geneeskd. 2021;165:D6065. Dutch.

11. CDC Emerging Sars-Cov-2 Variants. Available from: https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html#. Accessed January 28, 2021.

12. Bimonte S, Cascella M. The potential roles of epigallocatechin-3-gallate in the treatment of ovarian cancer: current state of knowledge. Drug Des Devel Ther. 2020;14:42454250. doi:10.2147/DDDT.S253092

13. Bimonte S, Cascella M, Barbieri A, Arra C, Cuomo A. Current shreds of evidence on the anticancer role of EGCG in triple negative breast cancer: an update of the current state of knowledge. Infect Agent Cancer. 2020;15:2. doi:10.1186/s13027-020-0270-5

14. Bimonte S, Cascella M, Barbieri A, Arra C, Cuomo A. Shining a light on the effects of the combination of (-)-epigallocatechin-3-gallate and tapentadol on the growth of human triple-negative breast cancer cells. In Vivo. 2019;33(5):14631468. doi:10.21873/invivo.11625

15. Bimonte S, Albino V, Piccirillo M, et al. Epigallocatechin-3-gallate in the prevention and treatment of hepatocellular carcinoma: experimental findings and translational perspectives. Drug Des Devel Ther. 2019;13:611621. doi:10.2147/DDDT.S180079

16. Cascella M, Bimonte S, Muzio MR, Schiavone V, Cuomo A. The efficacy of Epigallocatechin-3-gallate (green tea) in the treatment of Alzheimers disease: an overview of pre-clinical studies and translational perspectives in clinical practice. Infect Agent Cancer. 2017;12:36. doi:10.1186/s13027-017-0145-6

17. Bimonte S, Cascella M, Leongito M, et al. An overview of pre-clinical studies on the effects of (-)-epigallocatechin-3-gallate, a catechin found in green tea, in treatment of pancreatic cancer. Recenti Prog Med. 2017;108(6):282287. doi:10.1701/2715.27715

18. Bimonte S, Leongito M, Barbieri A, et al. Inhibitory effect of (-)-epigallocatechin-3-gallate and bleomycin on human pancreatic cancer MiaPaca-2 cell growth. Infect Agent Cancer. 2015;10:22. doi:10.1186/s13027-015-0016-y

19. Nagle DG, Ferreira D, Zhou YD. Epigallocatechin-3-gallate (EGCG): chemical and biomedical perspectives. Phytochemistry. 2006;67(17):18491855. doi:10.1016/j.phytochem.2006.06.020

20. Xu J, Xu Z, Zheng W. A review of the antiviral role of green tea catechins. Molecules. 2017;22(8):1337. doi:10.3390/molecules22081337

21. Steinmann J, Buer J, Pietschmann T, Steinmann E. Anti-infective properties of epigallocatechin-3-gallate (EGCG), a component of green tea. Br J Pharmacol. 2013;168(5):10591073. doi:10.1111/bph.12009

22. Wang YQ, Li QS, Zheng XQ, Lu JL, Liang YR. Antiviral effects of green tea EGCG and its potential application against COVID-19. Molecules. 2021;26(13):3962. doi:10.3390/molecules26133962

23. Xu J, Gu W, Li C, et al. Epigallocatechin gallate inhibits hepatitis B virus via farnesoid X receptor alpha. J Nat Med. 2016;70(3):584591. doi:10.1007/s11418-016-0980-6

24. Zhong L, Hu J, Shu W, Gao B, Xiong S. Epigallocatechin-3-gallate opposes HBV-induced incomplete autophagy by enhancing lysosomal acidification, which is unfavorable for HBV replication. Cell Death Dis. 2015;6(5):e1770. doi:10.1038/cddis.2015.136

25. Pang JY, Zhao KJ, Wang JB, Ma ZJ, Xiao XH. Green tea polyphenol, epigallocatechin-3-gallate, possesses the antiviral activity necessary to fight against the hepatitis B virus replication in vitro. J Zhejiang Univ Sci B. 2014;15(6):533539. doi:10.1631/jzus.B1300307

26. Chen M, Sllberg M, Hughes J, et al. Immune tolerance split between hepatitis B virus precore and core proteins. J Virol. 2005;79(5):30163027. doi:10.1128/JVI.79.5.3016-3027.2005

27. He W, Li LX, Liao QJ, Liu CL, Chen XL. Epigallocatechin gallate inhibits HBV DNA synthesis in a viral replication - inducible cell line. World J Gastroenterol. 2011;17(11):15071514. doi:10.3748/wjg.v17.i11.1507

28. Haberichter J, Roberts S, Abbasi I, Dedthanou P, Pradhan P, Nguyen ML. The telomerase inhibitor MST-312 interferes with multiple steps in the herpes simplex virus life cycle. J Virol. 2015;89(19):98049816. doi:10.1128/JVI.01006-15

29. Isaacs CE, Wen GY, Xu W, et al. Epigallocatechin gallate inactivates clinical isolates of herpes simplex virus. Antimicrob Agents Chemother. 2008;52(3):962970. doi:10.1128/AAC.00825-07

30. Gosslau A, En Jao DL, Huang MT, et al. Effects of the black tea polyphenol theaflavin-2 on apoptotic and inflammatory pathways in vitro and in vivo. Mol Nutr Food Res. 2011;55(2):198208. doi:10.1002/mnfr.201000165

31. Pradhan P, Nguyen ML. Herpes simplex virus virucidal activity of MST-312 and epigallocatechin gallate. Virus Res. 2018;249:9398. doi:10.1016/j.virusres.2018.03.015

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33. Lo YM. Quantitative analysis of Epstein-Barr virus DNA in plasma and serum: applications to tumor detection and monitoring. Ann N Y Acad Sci. 2001;945:6872. doi:10.1111/j.1749-6632.2001.tb03865.x

34. Chang LK, Wei TT, Chiu YF, et al. Inhibition of Epstein-Barr virus lytic cycle by (-)-epigallocatechin gallate. Biochem Biophys Res Commun. 2003;301(4):10621068. doi:10.1016/s0006-291x(03)00067-6

35. Liu S, Li H, Chen L, et al. (-)-Epigallocatechin-3-gallate inhibition of Epstein-Barr virus spontaneous lytic infection involves ERK1/2 and PI3-K/Akt signaling in EBV-positive cells. Carcinogenesis. 2013;34(3):627637. doi:10.1093/carcin/bgs364

36. Hamza A, Zhan CG. How can (-)-epigallocatechin gallate from green tea prevent HIV-1 infection? Mechanistic insights from computational modeling and the implication for rational design of anti-HIV-1 entry inhibitors. J Phys Chem B. 2006;110(6):29102917. doi:10.1021/jp0550762

37. Zhang HS, Wu TC, Sang WW, Ruan Z. EGCG inhibits Tat-induced LTR transactivation: role of Nrf2, AKT, AMPK signaling pathway. Life Sci. 2012;90(1920):747754. doi:10.1016/j.lfs.2012.03.013

38. Williamson MP, McCormick TG, Nance CL, Shearer WT. Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: potential for HIV-1 therapy. J Allergy Clin Immunol. 2006;118(6):13691374. doi:10.1016/j.jaci.2006.08.016

39. Castellano LM, Hammond RM, Holmes VM, Weissman D, Shorter J. Epigallocatechin-3-gallate rapidly remodels PAP85-120, SEM1(45107), and SEM2(49107) seminal amyloid fibrils. Biol Open. 2015;4(9):12061212. doi:10.1242/bio.010215

40. Duan JM, Qiu JY, Tan SY, Liu SW, Li L. [Semen-derived enhancer of viral infectiona key factor in sexual transmission of HIV]. Bing Du Xue Bao. 2012;28(1):8488. Chinese.

41. Hauber I, Hohenberg H, Holstermann B, Hunstein W, Hauber J. The main green tea polyphenol epigallocatechin-3-gallate counteracts semen-mediated enhancement of HIV infection. Proc Natl Acad Sci U S A. 2009;106(22):90339038. doi:10.1073/pnas.0811827106

42. Li S, Hattori T, Kodama EN. Epigallocatechin gallate inhibits the HIV reverse transcription step. Antivir Chem Chemother. 2011;21(6):239243. doi:10.3851/IMP1774

43. Liu S, Lu H, Zhao Q, et al. Theaflavin derivatives in black tea and catechin derivatives in green tea inhibit HIV-1 entry by targeting gp41. Biochim Biophys Acta. 2005;1723(13):270281. doi:10.1016/j.bbagen.2005.02.012

44. Wang YF, Shao SH, Xu P, Yang XQ, Qian LS. Catechin-enriched green tea extract as a safe and effective agent for antimicrobial and anti-inflammatory treatment. Afr J Pharm Pharmacol. 2011;5:14521461. doi:10.5897/AJPP11.164

45. Kuzuhara T, Iwai Y, Takahashi H, Hatakeyama D, Echigo N. Green tea catechins inhibit the endonuclease activity of influenza A virus RNA polymerase. PLoS Curr. 2009;1:RRN1052. doi:10.1371/currents.rrn1052

46. Kim M, Kim SY, Lee HW, et al. Inhibition of influenza virus internalization by (-)-epigallocatechin-3-gallate. Antiviral Res. 2013;100(2):460472. doi:10.1016/j.antiviral.2013.08.002

47. Ling JX, Wei F, Li N, et al. Amelioration of influenza virus-induced reactive oxygen species formation by epigallocatechin gallate derived from green tea. Acta Pharmacol Sin. 2012;33(12):15331541. doi:10.1038/aps.2012.80

48. Song JM, Lee KH, Seong BL. Antiviral effect of catechins in green tea on influenza virus. Antiviral Res. 2005;68(2):6674. doi:10.1016/j.antiviral.2005.06.010

49. He X, Gao B, Zhou L, Xiong S. Green tea polyphenol epigallocatechin-3-gallate-alleviated coxsackievirus B3-induced myocarditis through inhibiting viral replication but not through inhibiting inflammatory responses. J Cardiovasc Pharmacol. 2017;69(1):4147. doi:10.1097/FJC.0000000000000439

50. Ho HY, Cheng ML, Weng SF, Leu YL, Chiu DT. Antiviral effect of epigallocatechin gallate on enterovirus 71. J Agric Food Chem. 2009;57(14):61406147. doi:10.1021/jf901128u

51. Carneiro BM, Batista MN, Braga ACS, Nogueira ML, Rahal P. The green tea molecule EGCG inhibits Zika virus entry. Virology. 2016;496:215218. doi:10.1016/j.virol.2016.06.012

52. Weber C, Sliva K, von Rhein C, Kmmerer BM, Schnierle BS. The green tea catechin, epigallocatechin gallate inhibits chikungunya virus infection. Antiviral Res. 2015;113:13. doi:10.1016/j.antiviral.2014.11.001

53. Lu JW, Hsieh PS, Lin CC, et al. Synergistic effects of combination treatment using EGCG and suramin against the chikungunya virus. Biochem Biophys Res Commun. 2017;491(3):595602. doi:10.1016/j.bbrc.2017.07.157

54. Vazquez-Calvo , Jimnez de Oya N, Martn-Acebes MA, Garcia-Moruno E, Saiz JC. Antiviral properties of the natural polyphenols delphinidin and epigallocatechin gallate against the flaviviruses West Nile virus, Zika virus, and Dengue virus. Front Microbiol. 2017;8:1314. doi:10.3389/fmicb.2017.01314

55. Su S, Wong G, Shi W, et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol. 2016;24(6):490502. doi:10.1016/j.tim.2016.03.003

56. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270273. doi:10.1038/s41586-020-2012-7

57. Weiss SR, Navas-Martin S. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev. 2005;69(4):635664. doi:10.1128/MMBR.69.4.635-664.2005

58. Mhatre S, Srivastava T, Naik S, Patravale V. Antiviral activity of green tea and black tea polyphenols in prophylaxis and treatment of COVID-19: a review. Phytomedicine. 2021;85:153286. doi:10.1016/j.phymed.2020.153286

59. Menegazzi M, Campagnari R, Bertoldi M, Crupi R, Di Paola R, Cuzzocrea S. Protective effect of epigallocatechin-3-gallate (EGCG) in diseases with uncontrolled immune activation: could such a scenario be helpful to counteract COVID-19? Int J Mol Sci. 2020;21(14):5171. doi:10.3390/ijms21145171

60. Mendonca P, Soliman KFA. Flavonoids activation of the transcription factor Nrf2 as a hypothesis approach for the prevention and modulation of SARS-CoV-2 infection severity. Antioxidants. 2020;9(8):659. doi:10.3390/antiox9080659

61. Singh S, Sk MF, Sonawane A, Kar P, Sadhukhan S. Plant-derived natural polyphenols as potential antiviral drugs against SARS-CoV-2 via RNA-dependent RNA polymerase (RdRp) inhibition: an in-silico analysis. J Biomol Struct Dyn. 2020;28:116. doi:10.1080/07391102.2020.1796810

62. Sagaama A, Brandan SA, Ben Issa T, Issaoui N. Searching potential antiviral candidates for the treatment of the 2019 novel coronavirus based on DFT calculations and molecular docking. Heliyon. 2020;6(8):e04640. doi:10.1016/j.heliyon.2020.e04640

63. Jang M, Park YI, Cha YE, et al. Tea polyphenols EGCG and theaflavin inhibit the activity of SARS-CoV-2 3CL-protease in vitro. Evid Based Complement Alternat Med. 2020;2020:5630838. doi:10.1155/2020/5630838

64. Sharma S, Deep S. In-silico drug repurposing for targeting SARS-CoV-2 main protease (Mpro). J Biomol Struct Dyn. 2020;12:18. doi:10.1080/07391102.2020.1844058

65. Mhatre S, Naik S, Patravale V. A molecular docking study of EGCG and theaflavin digallate with the druggable targets of SARS-CoV-2. Comput Biol Med. 2021;129:104137. doi:10.1016/j.compbiomed.2020.104137

66. Zhu Y, Xie DY. Docking characterization and in vitro inhibitory activity of flavan-3-ols and dimeric proanthocyanidins against the main protease activity of SARS-Cov-2. Front Plant Sci. 2020;11:601316. doi:10.3389/fpls.2020.601316

67. Wang T, Zhao M, Ye P, Wang Q, Zhao Y. Integrated bioinformatics analysis for the screening of associated pathways and therapeutic drugs in coronavirus disease 2019. Arch Med Res. 2021;52(3):304310. doi:10.1016/j.arcmed.2020.11.009

68. Chiou WC, Chen JC, Chen YT, et al. The inhibitory effects of PGG and EGCG against the SARS-CoV-2 3C-like protease. Biochem Biophys Res Commun. 2021. doi:10.1016/j.bbrc.2020.12.106

69. Du A, Zheng R, Disoma C, et al. Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2. Int J Biol Macromol. 2021;176:112. doi:10.1016/j.ijbiomac.2021.02.012

70. Jang M, Park R, Park YI, et al. EGCG, a green tea polyphenol, inhibits human coronavirus replication in vitro. Biochem Biophys Res Commun. 2021;547:2328. doi:10.1016/j.bbrc.2021.02.016

71. Chourasia M, Koppula PR, Battu A, Ouseph MM, Singh AK. EGCG, a green tea catechin, as a potential therapeutic agent for symptomatic and asymptomatic SARS-CoV-2 infection. Molecules. 2021;26(5):1200. doi:10.3390/molecules26051200

72. Henss L, Auste A, Schrmann C, et al. The green tea catechin epigallocatechin gallate inhibits SARS-CoV-2 infection. J Gen Virol. 2021;102(4):001574. doi:10.1099/jgv.0.001574

73. Park J, Park R, Jang M, Park YI. Therapeutic potential of EGCG, a green tea polyphenol, for treatment of coronavirus diseases. Life. 2021;11(3):197. doi:10.3390/life11030197

74. Lambert JD, Lee MJ, Lu H, et al. Epigallocatechin-3-gallate is absorbed but extensively glucuronidated following oral administration to mice. J Nutr. 2003;133(12):41724177. doi:10.1093/jn/133.12.4172

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Potential roles of EGCG in the treatment of COVID-19 | DDDT - Dove Medical Press

Phovia is highly effective for treating superficial and deep skin infections.

This article is sponsored by Vetoquinol.

Superficial bacterial folliculitis, also called superficial pyoderma, is a commonly diagnosed dermatological condition in dogs.1,2 These infections are secondary to primary conditions affecting normal skin barrier function (eg, allergic skin disease, trauma, burns), keratinization (eg, nutritional deficiency, liver disease), and immune regulation (eg, neoplasia, autoimmunity, endocrinopathy).2 Cats less commonly develop superficial pyoderma perhaps because of decreased adhesion of staphylococci to feline corneocytes, but the primary issues causing infection are similar to those seen in dogs.3-8

The primary pathogen associated with superficial pyoderma in dogs and cats is a normal resident of the skin, Staphylococcus pseudintermedius, but other flora may be involved.2,8-12 As the normal homeostasis of this organism is disrupted from a primary disease, these gram-positive cocci invade deeper regions of the epidermis and hair follicle epithelium, increase in number, and enhance inflammation.

Classical clinical lesions of superficial pyoderma include papules and pustules that may eventually progress to alopecia, epidermal collarettes, scales, and crusts. Often the skin is erythematous and pruritic. Chronic cases may demonstrate lichenification, hyperpigmentation, and scarring alopecia from long-standing inflammation and infection.2 Cats may develop even more unique cutaneous reaction patterns and skin lesionsespecially when allergic skin disease is presentincluding miliary dermatitis, eosinophilic plaques, rodent ulcers, and eosinophilic granulomas.5

Identifying and addressing the primary disease is paramount in achieving complete, permanent resolution of the superficial pyoderma. Therefore, treatment is multifactorial and aimed at addressing the primary disease, reducing skin inflammation, and treating the infection directly. Current guidelines for the treatment of superficial pyoderma in dogs recommend the use of topical antimicrobials as sole therapy whenever possible; however, overuse of systemic antibiotics remains common.2,13-16

Topical therapy has many benefits including direct antimicrobial effects without use of an antibiotic, reduction in antibiotic-resistant bacterial populations, restoration of the normal skin barrier, enhancement of skin hydration, physical removal of keratinous debris, and removal of offending allergens from the haircoat.2,14 However, topical therapy is met with challenges that impede clinical application. Adherence is the biggest concern when recommending topical therapy to pet owners. Frequent bathing or application of medicated solutions to the skin can be difficult when busy owner lifestyles combine with a nonadherent patient. Skin inflammation can be painful and animals may be resistant to topical therapy. Cats are fastidious groomers and may lick away a medicated topical therapy before it can achieve appropriate contact time. Additionally, some topical agents can cause oral erosions and ulcerations or even gastrointestinal disturbance when groomed off. For these reasons, systemic antibiotics continue to be a common prescribing practice for superficial pyoderma.

All antibiotic use, despite duration or frequency, contributes to the development of antibiotic-resistant bacterial populations on the animal and in the environment.17-19 From that very first dose, bacteria are constantly evolving to implement inherent and acquired resistance mechanisms necessary for survival. One well-recognized mechanism is oxacillin resistance through the mecA gene, which produces a penicillin-binding protein receptor with poor affinity for -lactam antibiotics.2,14,15,20-23 Even more concerning than these oxacillin-resistant strains are those that develop multidrug resistance, which is defined as resistance to 3 or more antibiotic drug classes. This may happen over time with repeated antibiotic exposure or after a single dose of certain antibiotics such as fluorinated quinolones.2,20,23-25 The continued emergence of antibiotic-resistant bacteria inhibits the successful treatment of bacterial infections in pets and humans. As veterinarians consider how their antibiotic use contributes to this growing pandemic, they must look for alternative, safe, effective, affordable, and convenient antibacterial treatment modalities.

Phovia as a solution

Investigation into the photobiological effects of light therapy has been ongoing for the past 50 years. Photobiomodulation (PBM) therapy is a type of light treatment that uses visible or near infrared light to promote therapeutic benefits including induction of tissue healing and regeneration and inhibition of biological responses that induce pain or inflammation. The treatment distance, wavelength, fluence, pulse parameters, spot size, and irradiation time influence the effects of light energy on tissue. Visible light with wavelengths ranging from 400 to 700 nm can stimulate positive photobiomodulatory effects that promote wound healing, reduce inflammation and pain, modulate stem cell populations, and reduce bacterial contamination of wounds.26,27

Once visible light enters the skin, it is absorbed by the cells and initiates chemical changes dependent on the wavelength (or color) of light and the chromophore within the skin.27 Within each cell, membrane-bound organelles called mitochondria contain chromophores that absorb the light energy and begin making energy (adenosine triphosphate; ATP) via activation of cytochrome c oxidase. Outcomes of the mitochondrial respiratory pathway activation include stimulation of secondary messenger pathways, production of transcription factors and growth factors, and increased ATP production. However, excessive light energy exposure will overstimulate mitochondrial respiration and cause expenditure of all ATP reserves, which creates oxidative stress resulting in damaging elevations of nitric oxide, production of harmful free radicals, and activation of cytotoxic mitochondrial-signaling pathways leading to apoptosis.27,28 This is why creating PBM therapy protocols is important for targeting the beneficial effects while avoiding unintended harm.

Specific benefits of light energy within the visible light spectrum can be broken down into each color of light. Blue light (400-500 nm) has a lower penetration depth and primarily interacts with keratinocytes, reduces bacterial adhesion and growth, and increases intracellular calcium and osteoblast differentiation.29-31 Green light (495-570 nm) affects the superficial tissue and alters melanogenesis, reduces hyperpigmentation of the skin, and reduces tissue swelling.29,30 Red light (600-750 nm) penetrates deeper into the dermis and subcutis where it acts on cellular mitochondria to reduce inflammation and promote collagen synthesis through fibroblast proliferation and production of transforming growth factor-, fibroblast growth factor, platelet derived growth factor, and others.26-28,32,33 Red light has proliferative effects on mesenchymal stem cells and induces proliferation of epithelial colony forming units important for tissue repair and regeneration.34,35

Phovia, sold by Vetoquinol, is a form of fluorescent PBM therapy utilizing a blue light emitting diode (LED lamp, 400-460 nm) and topical photoconverter gel that emits low-energy fluorescent light (510-600 nm) when illuminated by the LED lamp.36,37 This interaction results in the formation of multiple wavelengths of visible light, each with a unique depth of penetration and effect on the tissue as described above. Application is fast and simple. The affected skin may be clipped free of hair and cellular debris removed with gentle cleaning. The skin is allowed to dry before application of the photoconverter gel. Just prior to application, 1 ampule of fluorescence chromophore gel is added to 1 container of photoconverter carrier gel and mixed thoroughly. The mixture is applied in a 2-mm layer to the affected skin, and the LED lamp is held 5 cm above the lesion and used to illuminate the area for 2 minutes. The gel is wiped away using saline-soaked gauze. The application can be repeated immediately after 5 to 10 minutes of rest or a second application can occur a few days later. Twice-weekly applications are continued until the wound is healed. Appropriate eyewear is required to protect the operator from the intensely bright light. Application is pain free and stress free for the patient, so sedation is not typically required.

Benefits of Phovia

Phovia shows great promise as a safe, effective therapy for treatment of numerous inflammatory dermatoses in dogs including superficial pyoderma,38 deep pyoderma,39 perianal fistula,40 interdigital dermatitis,41 calcinosis cutis,42 acute traumatic wounds,43 chronic wounds,37 surgical wounds,44 and otitis externa.45 Phovia as a sole therapy speeds time to healing by 36% in canine superficial pyoderma as compared with dogs receiving oral antibiotics alone.38 In one study, dogs with superficial pyoderma were treated with Phovia alone or with an oral antibiotic alone. Dogs treated twice weekly with Phovia demonstrated complete clinical healing in about 2.3 weeks (P < .05)whereas dogs receiving oral antibiotic healed in about 3.75 weeks.38 Additionally, Phovia speeds time to healing by nearly 50% in deep pyoderma when used with an oral antibiotic (5.7 weeks of treatment) compared with dogs receiving only oral antibiotic (11.7 weeks of treatment).39 The ability of this fluorescent PBM therapy to eliminate or significantly reduce duration of exposure to antibiotics will decrease the spread of antibiotic-resistant bacterial strains within pets and humans.

Phovias high safety profile makes it a beneficial tool to implement in everyday practice. Training the veterinary team to communicate therapy benefits with clients as well as to perform treatments is fast and easy. Training the veterinary technicians to perform treatments will give the veterinarian time to examine other patients. A single back-to-back application takes about 15 minutes, so pet owners can be in and out of the clinic quickly; however, the 2 weekly treatments can be separated by a few days if the veterinarian prefers to evaluate the patient more frequently. Additionally, when used as a sole therapy, clients are not required to administer oral or topical medications at home. This greatly improves treatment adherence and success. Instruct clients to use once-daily smartphone photos to document improvement at home. This can be useful when deciding how many treatments to perform. Most cases of superficial pyoderma will resolve completely by the third treatment.38 It is a good idea to communicate to clients that 3 to 4 weekly treatments may be required.

Conclusion

Phovia is a versatile, innovative therapeutic approach to numerous types of dermatitis.36 It is easy to implement in general practice, and is safe, pain free, and affordable. Phovia is highly effective for superficial and deep skin infections and eliminates the need for clients to administer numerous at-home treatments. This greatly improves the pet-owner bond and treatment outcomes by promoting adherence. Phovia accelerates time to wound healing, which decreases duration of antibiotic exposure and may reduce risk of antibiotic resistance development in these cases.2,13,36-39 Phovias efficacy against antibiotic-susceptible and antibiotic-resistant bacteria shows promise as an alternative therapeutic approach that promotes the principles of antimicrobial stewardship.36 If you are interested in purchasing this medical device for your practice, contact your Vetoquinol service representative.

Amelia G. White, DVM, MS, DACVD is an associate clinical professor of dermatology at Auburn University College of Veterinary Medicine.

REFERENCES

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Managing superficial pyoderma with light therapy - DVM 360

By Express News Service

ROURKELA: With the medical system of AYUSH grappling with neglect, lack of resources and manpower in Sundargarh, practitioners have now pinned their hope on the Ministry of AYUSH after a Central team recently visited the district.The team, sources said, met State-level AYUSH authorities and took stock of gaps in the practise of alternative medical systems in the district.

In Sundargarh district, all the homoeopathy and ayurveda facilities including the Utkalmani Homoeopathy Medical College & Hospital (UHMCH) at Rourkela under the AYUSH Directorate continue to face myriad problems like inadequate basic amenities, infrastructure, drugs, consumables and manpower.

Over the last five years, UHMCH has improved its infrastructure but continues to suffer from whopping vacancies. Reliable source informed that all 15 posts of readers and 11 of 15 posts of lecturers are vacant. Besides, at least seven of the 12 departments do not have specialist faculties.

There are about 28 homeopathy dispensaries across the district, all of which are either struggling with poor infrastructure or vacancies and supplies. In Rourkela, there were eight homeopathy dispensaries under Rourkela Municipal Corporation (RMC). All have closed by now. Two remaining Homeopathy Medical Officers of the RMC were attached to the city Urban Public Health Centres (UPHCs) since December 2020. Similarly, there are 33 Government Ayurveda Dispensaries (GADs) in Sundargarh of which only 24 have doctors and ayurveda assistants and that too only after the recent postings.

It is learnt, hardly half a dozen of GADs have recently constructed buildings on land of their own while most do not have their own buildings and are running from donated accommodations. Former Principal of UHMCH and advisor to All Odisha Homeopathy Physicians Association Dr Gyana Ranjan Giri said due to neglect, the low-cost AYUSH system of therapies are failing to gain popularity and benefit people to their potential. AYUSH doctors are playing important roles in running the rural CHCs and PHCs, but are paid lower than allopathic doctors.

PG seats in the States Homeopathy MCHs and specialisation are also decreasing and there is urgent need to strengthen the education system to produce quality homoeopathy doctors, he said. On the other hand, District Ayurveda Medical Officer (DAMO) Dr Birendra Pandey claimed the situation is gradually improving with medicine supplies, filling up of vacancies and infrastructure improvement.

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AYUSH system in Odisha's Sundargarh grapples with neglect and poor infrastructure - The New Indian Express

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Global Integrative Health or Complementary and Alternative Medicine Market 2021 Growing Opportunity and Competitive landscape Arab Yoga Foundation...

Mantras are not a common ingredient in skin care, but at Forest Essentials, they are part of the process that goes into products like the brands ayurvedic face moisturiser.

During the making of our cult favourite Ayurvedic Eternal Youth Formula Date & Litchi, specific mantras are chanted while the cream is mixed by hand, to lend positive vibrations to the product, which consequently energise your skin with their pure energy, claimed Samrath Bedi, executive director of the Delhi-based brand and son of its founder Mira Kulkarni.

Forest Essentials and its close competitor Kama Ayurveda are brands rooted in Indias 5,000-year-old philosophy of holistic healing and both have attracted millions of dollars in investment from global beauty conglomerates. Forest Essentials parent company Mountain Valley Springs Pvt. Ltd is part owned by American beauty conglomerate Este Lauder Companies and international orders now constitute over 30 percent of its online business. Bedi expects the brands October launch with UK-based e-tailer Look Fantastic to boost that figure.

The UK is one of our largest markets, he says. Consumers there already have a significant knowledge of Ayurveda and a wider acceptance [of it or] buy into its philosophy and what it stands for.

Vivek Sahni, co-founder and director of Kama Ayurveda, which saw a reported minority investment of 100 crore rupees (approximately $14 million) by Spanish fashion and fragrance conglomerate Puig in 2019, is also positive about the UK market, with plans to open a store there in 2022, and has high hopes for the brands bestsellers, including Kumkumadi Thailam Miraculous Beauty Fluid, Pure Rose Water & Organic Hair Colour Kit and Bringadi Thailam Intensive Hair Treatment Oil. [That will] allow us to experience a strong market before rolling out [wider] distribution, he says.

So what is ayuverdic beauty? While there are many interpretations, it is generally associated with a range of product formulations, healing rituals and treatments across beauty and wellness which are based on principles of Ayurveda, a system of alternative medicine and philosophy with historical roots in the Indian subcontinent.

Unlike other beauty movements making their way westward take South Korean K-beautys focus on glass skin, for example ayurvedic beauty doesnt have a specific look. Well, not exactly.

Ayurveda presents a collaborative approach to organic beauty that works on three levels: outer perfection, inner beauty and ojas [a Sanskrit term meaning vitality] or the charisma of absolute beauty, reflected in inner vitality, lustrous hair, glowing skin, clear shining eyes and an inner fire, Bedi explained. When the skin acquires the touch and feel of silk with a dazzling glow it is known as tejas [a Sanskrit term meaning illumination] or the outer reflection of beauty.

Kama Ayurveda, which saw a reported minority investment of 100 crore rupees ($14 million) by Puig in 2019, is also positive about expanding into the UK market. Kama Ayurveda.

In many ways what Kama Ayurveda and Forest Essentials are doing is packaging the legacy of an ancient civilisation in a jar, one that chimes with the global consumers continued interest in clean beauty.

Integral to the aura of luxury surrounding both brands is the focus on quality botanical ingredients as well as processes of extracting oils that ensure purity. The luxury packaging is merely surface dressing for the investment and commitment needed to cold press oils, use steam distillation and create formulations consisting of organic or easily regenerable wild-sourced ingredients.

A niche but rapidly growing opportunity

In 2017, the size of the global ayurvedic products market was $4.5 billion, according to Hamdard Laboratories chief marketing officer Suman Varma, and is projected to reach $14.9 billion by 2026, at a CAGR of 16.14 percent during that period. While India is the largest market, there is growing interest from consumers in Southeast Asian countries, China, the US and some European markets.

Ayurvedic beauty products are resonating well with so called clean beauty consumers, says Claire McCormack, editor at Beauty Independent. Those in the US and UK are looking for plant-derived ingredients in their products, so Ayurveda and the use of ayurvedic ingredients [like] ashwagandha, turmeric, gotu kola [etcetera] in clean beauty has exploded in recent years.

Its growing popularity has some industry leaders asking whether ayurvedic beauty could be the next big global skin care and beauty phenomenon. Though some believe the trend is close to or already at its peak, others say that the growing number of brands on the market suggests otherwise.

Rasasara, Sahajan Skincare, Pratima Skincare and other indie brands from New York, Melbourne and Toronto are already shaping the globalised version of this traditional medicine, says Tanya Rajani, beauty and personal care analyst at Mintel.

In addition to India-based Forest Essentials and Kama Ayurveda, there many other independent ayurvedic brands, some founded by members of the Indian diaspora.

For Forest Essentials international orders now constitute over 30 percent of its online business. Forest Essentials.

Fable and Mane, a plant-based hair care brand inspired by ancient Indian beauty secrets founded by Nikita and Akash Mehta, two British siblings of South Asian heritage, is among those making inroads; it is already stocked across the British high street chain Boots.

According to McCormack, in North America, ayurvedic beauty brands can increasingly be seen across price points, with brands like Ranavat, Uma Oils, Soma Ayurvedic, and Love, Indus in the prestige space while UK-based Urban Veda, Paavani and new skin care brand Planktos are available at a lower price point.

Further insight on the global ayurvedic beauty market comes from Kavita Khosa, a Singapore-based Non-Resident Indian (NRI) who founded ayurvedic brand Purearth in 2012, sourcing from womens co-operatives in the Himalayas using chemical free methods of extraction and preservation. Purearth, which has an advisory council that includes Morgan Tan, the former president of Shiseido, is carried by Hong Kongs Lane Crawford department store, and other international launches are in the pipeline, Khosa says.

With seasonal changes, we see more nourishing, occlusive products like our Rose & Seabuck Face Cream and Mandarin Body Butter in demand in the north in winters, while our Turmeric Exfoliant Face Sand is very popular in the summer months regardless of the region, Khosa adds.

Indian luxury brands with global ambitions

Within India, the practice of Ayurveda has experienced a renaissance in the past twenty years, part of a growing turn towards Indian heritage industries of wellness, yoga and craft. All are part of Indias post-financial liberalisation and economic growth trajectory, whereby a growing middle class aspires to Western brands whilst cultivating a deep-rooted desire to reinstate and value things considered intrinsically Indian.

In turn, Ayurveda, is also seen as an increasingly important cultural attraction that can be leveraged for business. Ayurvedic spa resorts and treatment centres continue to be a massive draw for tourists to India from across the world.

As the West began looking at Eastern remedies, Ayurveda rose in stature and when that happened its value increased in our eyes. Even though brands such as Kama and Forest Essentials were founded in the early 2000s, ayurvedic skin care was still not seen as cool until it [was] adopted by the clean beauty and Western wellness circles, says Vasudha Rai, former beauty director at Harpers Bazaar India and the author of Glow: Indian Foods, Recipes and Rituals for Beauty, Inside and Out.

Ayurveda continues to be used as a form of holistic medicine and is practiced across India in ordinary homes. Among middle income consumers, more affordable brands like Biotique, Himalaya or Lotus Herbals tend to be used whereas Forest Essentials and Kama Ayurveda are popular among luxury consumers.

Ayurveda is seen as a key growth factor with Puig. We will be expanding our footprint.

Since Este Lauder Companies first took a stake in Forest Essentials 12 years ago, the brand has expanded to 90 stand-alone stores across 29 Indian cities and now exports to 100 countries through e-commerce in top export markets including the US, Singapore, the Gulf states and Australia. Like other ayurvedic brands, the Indian diaspora is a key demographic. Long-standing contracts to supply 5-star hotel chains and luxury spas complete the picture.

[Este Lauder Companies] has aided us towards becoming a best-in-class brand builder and direct-to-consumer retailer, said Bedi.

Given the disruption created by the Covid-19 pandemic shortly after Puig made its initial investment in Kama Ayurveda, it is too early to assess what that capital injection means for the brand.

Pre-pandemic, there was global interest from major players in different geographies, looking to invest in successful companies in the natural clean beauty space. Ayurveda is seen as a key growth factor with Puig. We will be expanding our footprint in the coming year, Sahni said.

Founded in 2002, for the first 10 years it had only nine products and sold solely through 5-star hotels. In 2012, the brand opened their first store in Delhi, and soon received their first external funding from Lighthouse Advisors India Pvt. Ltd. Kama has since grown to 49 stand-alone stores across India, 47 store-in-stores, an e-commerce site as well as sales across Amazon, Flipkart, Nykaa and Myntra.

Debates around clean beauty, efficacy and safety

Ayurveda may be primed to harness the global trend towards clean beauty, but is the clean beauty movement ready to fully embrace the complex philosophy that underpins Ayurvedic skin care?

In a similar way that certain international beauty players are relating to Traditional Chinese Medicine, a lot of Ayurveda are being co-opted to be honest, and sometimes with little to no respect paid to the ancient healing system that Ayurveda is, McCormack warned.

International industry leaders and consumers alike require more education on ayurvedic beauty, suggest Indian industry insiders, as some misconceptions persist.

Formulations with triethanolamine (TEA), petrochemicals or formaldehyde dont exist in Ayurveda. But clean does not necessarily incorporate Ayurveda. A formulation with rooibos or tea tree can be clean but it isnt an ayurvedic formulation, says Khosa.

Ayurveda is indeed a complex philosophy. Fundamental to it are the concepts of prana or life energy and doshas or mind-body types, namely vata (characterised by the element of air), pitta (fire) and kapha (earth). Ayurveda adherents believe that when a person is dominated by one or two of these doshas, food or skin treatments can be used to create balance.

Ayurveda is a lifestyle; it isnt just about a detox, herbs or oils. An ayurvedic prescription includes circadian rhythms, emotions, dreams and the environment that a person lives in, explained Rai.

Interpreting all of this for a luxury skin care business is both an opportunity to create a highly differentiated product, and a challenge to retain its deeper philosophical underpinnings.

Its easier to communicate the values, ethos and efficacy of Ayurveda in our stores, where beauty assistants are available to do the same. Physical stores also allow the consumer to try and test our treatments, Sahni said.

Kama Ayurveda has 49 stand-alone stores across India, 47 store-in-stores and their own e-commerce site. Kama Ayurveda.

Kama Ayurveda and Forest Essentials, like many other ayurvedic brands, also make use of social media to educate and inform consumers, with in-house ayurvedic doctors creating regular videos, Instagram live sessions and online consultations.

In India, as in other countries around the world, there are tensions between the scientific and medical communities and practitioners of other traditional and alternative healing and wellness systems. In recent years, several high-profile scandals have seen unscrupulous entrepreneurs make bold, unsubstantiated claims linked to Ayurveda. The recent controversy around Patanjali Ayurveds Coronil which claimed to cure Covid being an example, which the Indian Medical Association (IMA) slammed for misleading and false claims.

Almost 40 percent of non-branded ayurvedic medicine samples tested over five years by the research centre of King Edward Memorial hospital in Mumbai contained steroids and toxic metals such as arsenic, lead and mercury. Such scandals have arguably unfairly sullied the reputation of the wider Ayurveda movement for some science-focused Indian beauty industry leaders and consumers.

Beyond the imperative to better reassure consumers of safety and efficacy, there is a need to make clear the distinctions between ayurvedic beauty and clean beauty and to explore ways to innovate formulations to appeal to a broader demographic.

Although consumers are drawn to ayurvedic ingredients, there is a segment of consumers who also believe in lab-grown ingredients; 43 percent [of Indian] consumers are interested in trying beauty products with a combination of scientific ingredients [such as] collagen or hyaluronic acid with botanical ingredients, said Rajani, citing Mintel data, concluding that there is an opportunity to merge science with Ayurveda.

This might be one strategy for brands to follow in global markets where the concept of cosmeceuticals is gaining traction. In any case, transparency in sourcing of ingredients will become more and more important, McCormack said.

Compliance with myriad health and safety regulations across the legal jurisdictions of various export markets is an added complication. For instance, controversy surrounding the ayurvedic practice of Rasa Shastra, a form of latrochemistry using heavy metals has led to some ayurvedic remedies being banned by The US Food and Drug Administration.

All our products are tested for heavy metals from the National Accreditation Board for Testing and Calibration Laboratories, an accredited lab [in India] and are completely devoid of lead, mercury and any other metals, which are known to possess harmful effects on the skin, said Bedi of Forest Essentials. On a board level with Este Lauder Companies expertise, we set up a state-of-the-art manufacturing facility in Haridwar, Uttarakhand, keeping our traditional manner of working intact while incorporating quality controls, which conform to the latest pharmaceutical guidelines, global standards and processes.

Sahni, of Kama Ayuverda, confirms that with respect to heavy metals, we dont use them in our formulations adding that now with the introduction of QR codes across latest launches, consumers can scan and learn more about the product We have worked tirelessly over the last four years to reincarnate Ayurveda for a customer looking for efficacy and, yes, ayurvedic products are manufactured under the licenses issued by the concerned state licensing authority established under [Indias] Drugs & Cosmetics Act and Rules thereunder.

Assuming that entrepreneurs like Sahni and Bedi can overcome the many challenges they face abroad regulatory and otherwise both are in a good position to tap into the growing global market for ayurvedic beauty products. Consumers around the world are clearly looking for alternative aesthetic and beauty rituals, new formulations and ingredients and authentic cultural heritage. That is a proposition both brands seem more than willing to offer.

The question that remains unanswered, however, is how much brands like Kama Ayuverda and Forest Essentials will have to localise their products and marketing strategies to truly go global.

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