Category Archives: Transhuman News

Genetic engineering will allow the production of tomatoes and kiwis that are more tolerant to saline lands and will require less water. The initiative will also develop biostimulants directly applicable to plants to make them more tolerant to stress caused by drought and salinity .

Agriculture has been one of the activities hardest hit by climate change. Figures in this regard indicate that around 40% of the worlds land area corresponds to land affected by drought, a value that could increase to 50% between now and 2025.

One of the initial focuses of the project is to generate new varieties of tomatoes and kiwis using the CRISPR / Cas9 genetic engineering technique. In the case of tomato, the characteristics of Poncho Negro, a Chilean variety originating in the Azapa Valley that has high resistance to salinity and the effect of heavy metals, will be studied.

Components to improve tomato 7742 (seminis), the most widely produced and marketed variety in Chile, will also be investigated. Regarding kiwis, the aim will be to increase tolerance to salinity and drought of varieties used as rootstocks, to improve the productivity of Hayward commercial kiwi plants; the third most exported in Chile.

[Editors note: This article was published in Spanish and has been translated and edited for clarity.]

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CRISPR gene editing could yield drought-tolerant tomatoes and kiwis that grow in salty soil - Genetic Literacy Project

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Bengaluru/New Delhi: As the coronavirus outbreak continues to spread across the world, the cyberspace has been abuzz with claims that the Covid-19 strain in India is a less virulent mutation than the one travelling abroad. BJP leader and Rajya Sabha MP Subramanian Swamy and gastroenterologist D. Nageshwar Reddy are among those who have made such claims.

While Swamy quoted an American friend in a tweet last week to say the Covid-19 strain in India can be defeated more effectively by our bodys natural defense mechanism than the strains abroad, Reddy in an interview floated similar claims without quoting any research.

Some users responded to Swamys tweet posting a link to a study that they claimed supported his notion. But this study, which is yet to be peer reviewed, has faults of its own, including use of limited data.

A number of experts in the field have termed such assertions baseless. Dr Gagandeep Kang, executive director at the Translational Health Science & Technology Institute in Faridabad, called Reddys comments appalling & misleading.

As such claims circulate online, ThePrint highlights the science of virus mutation and whether you should be worried.

Also read:WHO says coronavirus outbreak in Europe could be approaching peak

The overarching problem is the use of the term Indian SARS-CoV-2 strain that is in itself misleading.

A strain is a sub-type of a virus, characterised by different cell surface proteins, eliciting a different immune response from other strains. A mutation, however, is very minor genetic errors in genome sequences made during replication that doesnt fundamentally change the nature or behaviour of the virus.

So far, only two isolates from India have been genetically sequenced. Both are from coronavirus patients in Kerala who had arrived from Chinas Wuhan in late January. The strains are nearly identical to the ones sequenced in Wuhan and cannot be identified as a separate Indian strain.

Anu Raghunathan, a scientist at the Council of Scientific and Industrial Researchs (CSIR) National Chemical Laboratory in Pune, told ThePrint that the researchers of the aforementioned study used computational biology to analyse the genomic data from different strains around the world.

Theinitial attempt of the team from the International Centre for Genetic Engineering and Biology, New Delhi, at analysing the virus strain is not sufficient to conclude that all Indian strains would have only one unique mutation, said Raghunathan.

The mutations themselves are composed of changes in base pairs.

The novel coronaviruss genome is made up of 30,000 base pairs, while a human genome contains over 3 million. The small numbers make it easy for scientists to track changes and new lineages as they evolve.

To understand what these mutations mean for India, the country will have to sequence a much larger set of the viral isolates from the patients here.

Rakesh K. Mishra, director of CSIRs Centre for Cellular and Molecular Biology in Hyderabad, told ThePrint that his institute has the capacity to run the genome sequencing of the isolates from at least 500 people within a couple of weeks. This can help scientists decide the correct course of action for treating the disease.

For example, if a virus mutates too fast, vaccines being developed now will potentially become useless, and pharmaceuticals will have to constantly keep up with the mutations by developing new vaccines all the time, a financially unviable prospect.

Also read:China now wants people to shop, eat out while rest of the world locks down

Regularly switching up the genetic code is an essential part of how a virus evolves. Some viruses, such as the coronaviruses that cause flu, change their genetic code extremely rapidly. This is the main reason why its so difficult to find a vaccine for coronaviruses. They evolve quickly, making vaccines defunct.

The flu vaccine, now available and recommended especially for older people, needs to be taken annually for this reason. By the time the next season comes along, the vaccine is no longer effective on the circulating form of the virus.

Coronaviruses are ribonucleic acid (RNA) viruses, containing just RNA strands (single or double) as its genetic material. They have about 26,000 to 32,000 bases or RNA letters in their length.

RNA viruses mutate continuously. Such a mutation is what made SARS-CoV-2s jump from animals to humans possible.

The virus multiplies inside living organisms cells by creating copies for the RNA. However, the process it uses to make these copies is not perfect, and often introduces tiny errors in the sequence of letters much like a game of Chinese whispers.

The errors that do not help the survival of the virus eventually get eliminated, while other mutations get embedded. It is these mistakes that help scientists track how the virus travelled around different geographic locations.

For example, by genetically sequencing over 2,000 isolates of samples from different countries, scientists tracked how the novel coronavirusspread to different countries, and how the virus evolved and geographically mutated in different areas.

The word mutations often conjures images of humans with superpowers thanks to Hollywood movies but it doesnt mean the virus acquires superpowers. The genetic changes are normal in the evolution of the virus. In some cases, the changes are extremely rapid because the replication is not rigorous or thorough.

The only problem with mutations is the problem of development of vaccines, which would require constant upgrade.

Also read:Why asymptomatic coronavirus carriers arent as contagious but still a big danger

The novel coronavirus, unlike its cousins, mutates slowly. It seems to have a proofreading mechanism in place that reduces the error rate and slows down the speed of mutation. But the mutations are completely random.

One mutation that supports the virus replication and transmission from human to human or any other host sustains whereas the virus that cannot infect many eventually dies out, explained Shweta Chelluboina, clinical virologist at the Interactive Research School for Health Affairs in Pune.

These are random events and such a phenomenon has caused the outbreak in the first place.The newcoronavirushad mutated successfully enoughthat it jumped from animal tohuman, allowingit to infect manywith still no containment in sight, said Chelluboina.

There were reports earlier about how the novel coronavirus has mutated into two strains so far the original S-type which originated in Wuhan, and the subsequent L-type that evolved from the S-type and is more prevalent in countries like the US. Scientists at the Peking Universitys School of Life Sciences and the Institut Pasteur of Shanghai announced these findings.

The L-type is the more aggressive one, and spreads rapidly but is no more or less virulent than the S-type. The researchers urged everyone to take preventive measures because the mutation indicates that more could be coming.

But these arent really two strains as such. A strain is a genetic variant characterised by different forms of surface proteins. But the L-type and the S-type are not quite different enough to call them strains just yet. They are just mutations, referred to as types, according to the study.

To explain the lower population of S-type, the authors of the study suggested that human-adopted measures of curbing contact contained the S-type to the Wuhan region, and allowed the L-type to spread elsewhere uncontained. While the S-type emerged around the time the virus jumped from animals to humans, the L-type emerged soon after that within humans, the team suggested.

Experts think there is also a definite sampling bias for the L-type, which was just sampled more, and uniformly, resulting in higher representation. The mutations were discovered in a preliminary study, as cautioned by the authors as well, and was performed on a limited population of 103 samples.

The study is not peer-reviewed yet, and as most Covid-related studies are under the open community, is a pre-print for now. It was uploaded on 4 March.

These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 (Covid-19), said the study.

The science is evolving rapidly, as more and more genome data is collected from around the world.

Newer research data gathered from genetic sequences uploaded to open source website NextStrain.org indicate that anywhere from eight to 18 different sequences of the coronavirus are making their way around the globe, according to researchers who have genetically sequenced over 1,400 isolates from around the world. These are extremely tiny differences within the viruses in their nucleotide sequences, and none of the sequenced groups seem to be growing any more or less lethal than others.

Most importantly, none of them are new strains despite their coverage as such in the mediaand subsequent clarifications by Nextstrain, who have the data for 2,243 SARS-CoV-2 genomes, of which 1,150 have minor mutations.

On Nextstrain, nearly every virus reveals a slightly different genome. But there are very few mutations and none are strong or vital enough to affect the way the virus spreads, attacks, or lives. The sequences are all named by location where they were first sequenced.

It is very common that during an outbreak, especially during a global pandemic, the genome sequence of earlier isolates from one particular geographical location will differ from that of the later isolates collected elsewhere, said Sreejith Rajasekharan, virologist and post doc at the International Center for Genetic Engineering and Biotechnology (ICGEB) in Trieste, Italy, over an email.

This is what is observed in the current pandemic as well. The first sequence collected from positive patients in Rome, Italy was from a Chinese tourist. This and the one collected after, from an Italian citizen returning from China resemble those that were isolated in China, said Rajasekharan.

However, the ones isolated later in Lombardia and Friuli Venezia Giulia regions (in Italy) match the European clad and not the one from China.

The mutations in the virus are like moving targets, which cant be hit because they keep changing their genetic sequence.

Genome sequencing on a large scale can tell us whether viral isolates are different in different countries from what we saw from China. So this will help us decide whether the treatments being contemplated in those places will be applicable for our strains or not, Rakesh Mishra said.

It will also help decide if the different strains vary so much that developing vaccines may not be viable, Mishra said.

Some behaviours are unique in different strains like how we know that aged people are at high risk but we saw in India young people have also died, said Chelluboina. Some variations in the virus cause the virus to behave in a certain way.

The sequencing will provide a fundamental understanding of how to address the problem without it, the treatments are based on what is known of other viruses which may or may not work for the novel coronavirus, and also likely take up a long time.

That is why it is important to understand the sequence of the virus in local infections to know which countries have a similar virus, so that we can attempt to better predict the outcome, added Chelluboina.

However, Rajasekharan added, The general public needs not be concerned in this regard as the genome of SARS-CoV-2 is quite stable, and therefore the rate of mutation is low.

The novel coronavirus will continue to mutate and pose a challenge to researchers developing a vaccine. Nonetheless, the idea of viruses mutating is not something that needs to worry people in terms of their health when it comes to Covid-19.

Also read:Seasonal flu far more common than coronavirus, but its vaccine is not popular in India

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How the novel coronavirus is mutating, and if you should be concerned - ThePrint

A virus spreads by replicating itself each time it replicates, it could change a little. Mapping the genome of each changed form of the virus, therefore, helps track where it came from and how. The Translational Bioinformatics Group at the International Centre for Genetic Engineering & Biotechnology in New Delhi studied the genomes of the virus from five locations Wuhan, India , Nepal, Italy and the US to identify what is unique to the novel coronavirus and what difference geographical location makes. A country-specific mutation would explain the severity of illness, the extent and timing of exposure to symptomatic carriers and, consequently, hold the clue to a containment strategy. For instance, the study found the presence of unique mutations identified in the genome from Italy are responsible for the sudden upsurge in the number of affected cases and deaths, combined with other factors a speculation which may be verified with more evidence. Any strategy to counter the virus, then, would have to factor this in.Mutations help viruses survive in hosts and influence its virulence (how it attaches, infects and multiplies in a host). The mutations could be favourable or detrimental to the viruses, depending on the type of mutation. If a mutation results in a more virulent virus, its transmission is enhanced, Dr Dinesh Gupta, group leader of the study which published its preliminary findings in a preprint paper, told TOI.

Mutations help viruses survive in hosts and influence its virulence (how it attaches, infects and multiplies in a host). The mutations could be favourable or detrimental to the viruses, depending on the type of mutation

So what did they find? In the samples the group studied, the sequence from Nepal showed no variation at all. And the maximum mutations were seen in the Indian sequence, six. Mutations bring about variations in viral genomes as the virus evolves to survive in its host. A mutation may be good or bad. Very fast mutations produce viruses which are not able to survive. The viruses that do survive, adapt and transmit are the ones that are sequenced and analysed, Dr Gupta said.

Of the six mutations in Indian genome, only one was unique to India

Mutations in Indian genome

Spike surface glycoprotein (unique to India): A virus protein which helps a virus attach itself to a host cell and enter it

ORF1ab: Polyprotein which is cleaved to form 16 smaller proteins, each known as non-structural protein (Nsp)

Nsp2: Believed to hamper signalling process in host cell

Nsp3: Protein which breaks down other proteins

Helicase or Nsp12, unwinds DNA molecules

ORF8 protein: Helps virus in human adaptation

For specific conclusions, however, Dr Gupta said, a wider base of study would be needed. The current data of just two sequences from Indian samples is too small to make a definitive statement, and requires more sequences to be analysed. He also clarified that one finding of the preliminary report that the microRNA hsa-miR-27b (small RNA molecules that can influence the expression of virus proteins) was found to have a target only in the Indian genome in the first study could not be replicated. We didn't find any target for the miRNA hsa-miR-27b in the second sequence, whereas the miRNA was predicted to uniquely target the spike glycoprotein in the first sequence, he said.

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India What we know about the genome of the virus in India A mutation unique to - Times of India

What is a vaccine?

According to the World Health Organization (WHO) a vaccine is understood to be any preparation intended to generate immunity against a disease by stimulating the production of antibodies. This may be, for example, a suspension of killed or attenuated microorganisms, or products or derivatives of microorganisms. Most vaccines are given by an injection, but some are given orally (by mouth) or sprayed into the nose.

In a previous article we had talked about the immune system, which is like the bodys defense army. One is born with a capacity to respond to what the body recognizes as foreign, as a threat (such as a virus, a bacterium, a fungus, or a parasite). That primary responsiveness is quick, but it is not specific and, therefore, sometimes not enough, the threat manages to get past that barrier. We call that first, fast and nonspecific immunity innate immunity.

The body has another way of defending itself, specially designed for each type of threat. Lets say that the body has, from birth, a group of cells ready to design and produce specific weapons for each pathogen. This second army works on what we call acquired immunity.

Since there is a wide variety of pathogens, [1] these cells do not produce these specific weapons until the pathogen enters the body, they recognize it, and they can design exactly the weapon that will harm it. This response is more specific, but it takes longer to start working.

One of the most powerful weapons in this army are the antibodies (also known as immunoglobulins). Antibodies are molecules (glycoproteins) that synthesize cells of the immune system (lymphocytes), these antibodies are synthesized with the exact composition that allows it to specifically (very specifically) bind to a part of the pathogen.

Antibodies have two main functions: they mark these pathogens to be attacked and eliminated by other cells of the immune system, or they bind to a specific part of the pathogen that blocks its ability to enter and harm cells in the body.

Antibodies are generated against specific substances of the pathogens; these substances are called antigens. They are that part of the pathogen that, by interacting with the cells of the immune system, provokes the immune response, which is why identifying them is an important part in the production of vaccines.

Once this army that participates in acquired immunity, designs this production line against a specific pathogen, it already leaves it there programmed (immunological memory), so if this pathogen attacks us again all these specific weapons are ready, the response is faster, if you get sick it is usually much less serious, and many times you do not get sick because the immune system of your body fought the threat and eliminated it before it could harm you and cause symptoms.

Thats what a vaccine does, getting in contact with the pathogen (or parts of it), in a safe (non-disease-causing) way, but enough to trigger your immune response and leave all your weapons ready so if that pathogen attacks you naturally, your response is quick, specific and protective.

What types of vaccine are there?

There are different types of vaccines. Some of them contain the complete infectious agent (live attenuated vaccines and inactivated or dead vaccines). In live attenuated vaccines, an attenuated or weakened form of the disease-causing pathogen (such as chickenpox or smallpox vaccines) is used. So that it elicits a very strong immune response, most of these vaccines need a single dose to immunize you for life. However, when using an attenuated form of the pathogen it should be used with caution in people with weakened immune systems, and it has specificities for its preservation (they should always be kept cold).

Inactivated vaccines use the inactivated version of the pathogen (for example, against polio or rabies). They use a harmless version of the pathogen, but usually do not provide an immunity as strong as live vaccines, which is why multiple doses are often required.

On the other hand, vaccines with toxoids (against diphtheria and tetanus, for example) are those that use the toxins (toxic substances) released by the pathogen when they are the cause of the disease. It generates immunity against this harmful toxin, not against the pathogen itself.

There is another group of vaccines with greater biotechnological complexity: conjugate and recombinant vaccines. These employ fragments of the pathogens molecular structure, which elicit a protective immune response, which is the goal of all vaccines.

They are very safe vaccines, that can be used in anyone and offer a very strong immune response directed at key parts of the pathogen. Conjugates combine these parts of the infectious agent (virus or bacteria) with other molecules that increase their immunogenic capacity (for example, vaccines against some meningococci and pneumococci), while recombinants (such as vaccines against hepatitis B, human papilloma virus or herpes zoster) involves introducing into any vectorit is usually a virus or bacterium that does not cause diseaseregions of the pathogen that we know to be immunogenic; that is, they have the capacity to activate the immune system.

Among the novel techniques being used for the production of vaccines are DNA vaccines, nanoparticle vaccines, among others.

Those involving genetic engineering, the so-called DNA vaccines, have had a major boost with technological development that has succeeded in sequencing (knowing the genetic information) of many pathogens very quickly. The sequence of the current coronavirus, for example, was obtained in just days. Researchers use an organisms genome (its genetic information) to extract the genes that are most likely to match known antigens that could be used in a vaccine.

Once identified, those genes can be combined and inserted into a different, rapidly multiplying organism, such as yeast, to produce experimental antigens, which are then studied to determine their ability to elicit a protective immune response. This method is known as reverse vaccination; no licensed vaccine has yet been released, but several experimental vaccines are already being studied, some of which are in the later stages of clinical trial (for example, a group B meningococcal vaccine). [2] Several of the vaccine candidates against COVID-19 follow this method.

What process does a vaccine candidate have to follow until it is approved for use in humans?

The creation of a vaccine is a long and complex process that often takes 10 to 15 years, and involves the combined participation of governments, and public and private organizations.

The World Health Organization establishes a protocol that many governments and regulatory institutions in the world follow, although each of them has specific regulations.

Ensuring that vaccines are safe, effective and of quality is a crucial element in their development and distribution. It begins with the first phases of the vaccine, generally in the laboratory, where its components are subjected to tests to determine aspects such as purity and potency. The clinical trials consisting of three phases are then commenced.

The license, or authorization for use in humans is the fundamental step in the process. The official entity that grants the authorization, the national regulatory body is the arbitrator that decides whether the established standards have been met to guarantee the quality of the vaccine.

What are the steps that have to be followed?

Exploration stage

This stage involves basic laboratory research, and often lasts 2 to 4 years.

Preclinical stage

Preclinical studies use tissue culture or cell culture systems and animal testing to assess the safety of the candidate vaccine and its ability to elicit an immune response.

Researchers can tailor the candidate vaccine during the preclinical phase to try to make it more effective. They can also perform exposure studies on animals, which means animals are vaccinated and then they try to infect them with the target pathogen; these types of studies are never performed on humans.

Many candidate vaccines do not go beyond this stage, as they cannot elicit the desired immune response. Often the preclinical stages last 1 to 2 years.

To continue the studies, after completing this phase, an application must have been approved by a competent agency.

Human clinical studies

Phase I

This first attempt to evaluate the candidate vaccine in humans involves a small group of adults, generally between 20 to 80. If the vaccine is aimed at children, the researchers will first test it in adults, and will gradually reduce the age of the test subjects until they reach the target. The goals of phase I trials are to assess the safety of the candidate vaccine and to determine the type and extent of the immune response that the vaccine elicits.

Phase II

A larger group of several hundred people participates in phase II testing. Some of the people may belong to groups at risk of contracting the disease; the trials are randomized and well controlled, and include a placebo group. The goals of phase II trials are to study the candidate vaccine for its safety, immunogenicity, proposed doses, vaccination schedule, and method of application.

Phase III

Candidate vaccines that are successful in phase II advance to larger trials, involving thousands to tens of thousands of persons. Phase III trials are randomized and double-blind, and involve the experimental vaccine that is tested against a placebo (the placebo may be a saline solution, a vaccine for another disease, or some other substance). One of phase IIIs goals is to evaluate the safety of the vaccine in a large group of persons. Some unusual side effects may not be apparent in smaller groups of people who were part of the previous phases.

During these phases, the efficacy of the vaccine to protect against the disease is assessed. Tests are done that have to do with the production of antibodies and the immune response of the persons who receive the vaccine. After a phase III trial is successful, accredited agencies will inspect the product, the factories and research results, until approval is issued.

After approved for large-scale use, the vaccines continue to be monitored.

Structure of the SARS-Cov-2 coronavirus

SARS-COV-2 is an enveloped, RNA-positive virus. The key to enter the cell is found in the so-called spike proteins (S), which cover the virus envelope.

SARS-CoV-2 coronavirus vaccines and treatments

The process to start a vaccine can take many years, however, we are told that probably in just over a year we can have a vaccine against this new virus. A response that, if possible, would be of a speed never seen before against a new disease.

This is mainly due to advances in the biotechnology sector. First of all, just one week after China reported the first cases of severe pneumonia of unknown origin to the WHO, the causative agentthe new SARS-CoV-2 coronaviruswas identified. A few days later its genome was already available. In just under three months, more than 970 scientific articles are available in the PubMed database.

Knowing the biology of the virus facilitates the design of therapeutic (antiviral) and preventive (vaccines) strategies. The similarity of genetic information with another coronavirus that has been studied for years, SARS-Cov, which caused the epidemic of acute respiratory syndrome (SARS) in 2002, has led to rapid progress in the pre-clinical phases.

In just these three months there are already several therapeutic proposals and vaccine candidates against the new coronavirus. Science has never advanced so far in such a short time to combat an epidemic. Many of the proposals come from research groups that have spent years working against other viruses, especially against SARS and MERS. This accumulated knowledge has now made it possible to go at a speed never seen before.

Antiviral therapies

Some already available antiviral drugs have been tested to see if they can be effective in fighting COVID-19. Chloroquine, which has been used for years against malaria, is being studied by a group of researchers, as it could reduce the viral load by blocking the virus from entering cells. Some anti-inflammatories, such as barcitinib and mesmosate from camostat (Japan), are being used in some protocols because they could block the entry of the virus into lung cells.

One of the most promising antivirals against SARS-CoV-2 is remdesivir, an inhibitor that prevents the virus from multiplying within the cell. It has already been used against SARS and MERS and has been successfully tested in the latest Ebola epidemics, and against other viruses with the RNA genome. It is, therefore, a broad-spectrum antiviral. At least twelve phase II clinical trials are already underway in China and the U.S., and another has started in phase III with 1,000 patients in Asia.

In the United States, in New York, the FDA has approved the use of plasma from sick patients who have recovered. This involves obtaining blood from donors who have recovered from COVID-19, and isolating the plasma (where the antibodies are located), to transfuse it to sick people. It is not a new treatment; it was used in the Spanish Flu pandemic in 1918. According to the journal Nature, this effort in the United States is following preliminary studies carried out in China. The convalescent plasma approach has also had modest success during previous outbreaks of severe acute respiratory syndrome (SARS) and Ebola. It could be an emergency response in which more effective treatments appear.

There are at least 27 clinical trials with different combinations of antiviral treatments such as Interferon Alfa-2B, ribavirin, methylprednisolone, and azvudine. At the moment they are experimental treatments, but they are a hope for the most serious and severe cases.

COVID-19 vaccines for the future

The main hope for controlling the disease is based on achieving effective vaccines. The WHO, until March 20, had a list of 41 candidates, but based on press reports from various countries, we know that more are being worked on.

An article published on March 23 by The Conversation summarizes some of the most promising projects.

In clinical trial phase

According to the publication, one of the most advanced is the Chinese proposal, a recombinant adenovirus vector-based vaccine with the SARS-CoV-2 S gene, which has already been tested in monkeys and is known to produce immunity. A phase I clinical trial will be started with 108 healthy volunteers, between 18 and 60 years old, in which three different doses will be tested.

Other proposals are being promoted by CEPI (Coalition for Epidemic Preparedness Innovations), an international association in which public, private, civil and philanthropic organizations collaborate to develop vaccines against epidemics. It is currently funding eight SARS-CoV-2 vaccine projects that include recombinant, protein, and nucleic acid vaccines.

mRNA-1273 vaccine (Moderna, Seattle)

It is a vaccine made up of a small fragment of messenger RNA with the instructions to synthesize part of the protein S of the SARS-Co-V. The idea is that, once introduced into our cells, it is these cells that make this protein, which would act as an antigen and stimulate the production of antibodies. It is already in the clinical phase and it has begun to be tested in healthy volunteers.

Preclinical phases

Recombinant measles virus vaccine (Pasteur Institute, Themis Bioscience and University of Pittsburg)

It is a vaccine built on a live attenuated measles virus, which is used as a vehicle and contains a gene that encodes a protein of the SARS-CoV-2 virus. It is in the preclinical phase.

Recombinant Influenza Virus Vaccine (University of Hong Kong)

It is also a live vaccine that uses an attenuated influenza virus as a vector, which has had the virulence gene NS1 removed, and is therefore not virulent. A SARS-CoV-2 virus gene is added to this vector virus. This proposal has some advantages: it could be combined with any strain of seasonal influenza virus and thus serve as a flu vaccine, it can be quickly manufactured in the same production systems that already exist for influenza vaccines, and they could be used as intranasal vaccines via spray. It is in the preclinical phase.

Recombinant protein vaccine obtained by nanoparticle technology (Novavax)

This company already has vaccines against other respiratory infections such as adult flu (Nano-Flu) and respiratory syncytial virus (RSV-F) in clinical phase III and has manufactured vaccines against SARS and MERS. Its technology is based on producing recombinant proteins that are assembled into nanoparticles and administered with its own adjuvant, Matrix-M. This compound is a well-tolerated immunogen capable of stimulating a powerful and long-lasting nonspecific immune response. The advantage is that in this way the number of necessary doses would be reduced (thus avoiding revaccination). It is in the preclinical phase.

Recombinant vaccine using as a vector the Oxford chimpanzee adenovirus, ChAdOx1 (Jenner Institute, Oxford University)

This attenuated vector is capable of carrying another gene that encodes a viral antigen. Models for MERS, influenza, chikungunya and other pathogens such as malaria and tuberculosis have been tested in volunteers. This vaccine can be manufactured on a large scale in bird embryo cell lines. The recombinant adenovirus carries the glycoprotein S gene of the SARS-CoV-2. It is in the preclinical phase.

Recombinant Protein Vaccine (University of Queensland)

It consists of creating chimeric molecules capable of maintaining the original three-dimensional structure of the viral antigen. It uses the technique called molecular clamp, which allows vaccines to be produced using the virus genome in record time. It is in the preclinical phase.

Messenger RNA Vaccine (CureVac)

This is a proposal similar to that developed by the modern biotechnology company, with recombinant messenger RNA molecules that are easily recognized by the cellular machinery and produce large amounts of antigen. They are packaged in lipid nanoparticles or other vectors. In preclinical phase.

DNA INO-4800 vaccine (Inovio Pharmaceuticals)

It is a platform that manufactures synthetic vaccines with DNA of the S gene from the surface of the virus. They had already developed a prototype against MERS (the INO-4700 vaccine) that is in phase II. They recently published the phase I results with this INO-4700 vaccine and found that it was well-tolerated and produced a good immune response (high antibody levels and a good T-cell response, maintained for at least 60 weeks after vaccination). In preclinical phase.

Cuba

According to the director of biomedical research of the CIGB, Gerardo Guilln, the Center for Genetic Engineering and Biotechnology (CIGB) of Cuba has a vaccine design that could be used against the new coronavirus.

According to the Cuban scientist, this vaccine is in the methodological and design phase. However, according to his statements, there is an advanced path since a platform that the institution has already developed is being used, where it works with virus-like particles with great capacity to stimulate the immune system.

Another platform that is very attractive and promising being developed by the center is by immunization through the nose. Cuba has experience in this regard, since it has a registered vaccine that uses this nasal spray.

The Cuban vaccine candidate is being developed with the Cuba-China joint research and development center, located in Hunan province. It is not known when clinical trials could begin.

Cuba is also carrying out research in therapeutic drugs. The results so far published by China in the treatment of COVID 19, with the Cuban Interferon Alfa 2B, showed positive results.

***

All proposals for specific treatments and vaccines for COVID-19 are in the experimental phase. But technological advances and the accumulation of research results in the fields of antiviral therapies and vaccines against other viruses, and specifically against other coronaviruses, make many experts affirm that there is a high probability of success. Although we want and need faster responses, science cannot be asked to have a vaccine in less than a year, in reality that would already be a record time.

The international scientific communitys actions, in terms of sharing scientific results, collaboration and training, is the backbone of this battle, and my greatest hope.

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Why can't we have a COVID-19 vaccine right now? - OnCubaNews

Wow.

Thats the word Candace Johnson, the president and chief executive officer of Roswell Park Comprehensive Cancer Center, uses early in Cubas Cancer Hope. It airs as part of the PBS series Nova at 9 p.m. Wednesday.

She added the words, in Cuba, jeez, referring to the small communist countrys work on a vaccine for the treatment for certain forms of cancer.

But the word can also be applied to the positive national publicity Roswell Park is receiving in the program.

"Wow," indeed.

It certainly could use some good publicity after Roswell Park fired a top executive over the weekend for things she wrote on her Facebook page that bashed President Trump's response to the Covid-19 outbreak.

The Nova documentary plays like a promotion for Roswell Parks partnership with Cuba in search of a treatment. Roswell Park is especially highlighted in the second half of the hourlong program.

Several Roswell Park doctors, including Dr. Kelvin Lee, Dr. Kunle Odunsi, Dr. Mary Reid, Dr. Grace K. Dy and Dr. Joseph Tario, appear. The program centers around how Roswell became involved with scientists in a small Communist country where American citizens go to receive treatment illegally because of a United States trade embargo that complicates the relationship between the countries.

Dr. Kelvin Lee (Photo courtesy of Roswell Park)

I think everyone here thought that Cuba was stuck in I Love Lucy days, the 1950s, old cars, there cant possibly be good science going on, Lee says early in the program.

The beautifully filmed hour also may appeal to supporters of Democratic presidential candidate Bernie Sanders, who was criticized for old comments about Fidel Castros regime in Cuba expanding education and health care.

Cubas Cancer Hope acknowledges Castro's dictatorial sins that led to half its doctors leaving the country early in his reign. But it also credits the dictator for emphasizing science and giving Cubans something not available to all Americans free health care.

Lee and other doctors give a basic understanding of immunotherapy, genetic engineering, checkpoints and what Cuban scientists have discovered in the treatment of cancer that has resulted in some Americans going there to extend their lives.

"Cubas Cancer Hope humanizes the story by following some people who have been given the treatment and lived beyond expectations.

The question of how Roswell Park was chosen as a partner is raised, but not as thoroughly as I hoped. Odunsi explained that he was told Roswell Park was approached because it was one of the few institutions where discoveries in Cuba could be taken to the next level.

The relationship began in 2011 when Cuban doctors made a presentation at Roswell Park before a standing room audience.

Scientists, were a little crazy, Johnson explained. We all want to hear something really interesting. It sparked curiosity of how it came to be ... Wow, in Cuba. Jeez.

The bigger question is whether all the challenges of bringing the potential life-extending drug to Buffalo and across the United States will ever be conquered.

If it does, wow will be an understatement.

Dr. Candace Johnson (Photo courtesy of Roswell Park)

In a telephone interview, Johnson made aspects of the development of the partnership between Roswell Park and the Cuba doctors sound even more dramatic than portrayed in the documentary.

She noted that the April 2015 trade mission led by Gov. Andrew Cuomo that resulted in Roswell Park signing an agreement with Cubas Center for Molecular Immunology to set up a clinical trial for a lung cancer vaccine CimaVax was done under unusual circumstances.

At the time that (Cuomo) did that, that was pretty bold because no one had really gone there, she said. I was asked to go with Kelvin Lee and they had to charter a plane that left from JFK (Airport in New York City). The CEO of JetBlue was on the plane. They had to carry their own mechanics because there were no mechanics in Havana, there was no way to pay them. There was no way to pay rent. They refueled and left and refueled at Fort Lauderdale.

It was precedent-setting to say the least, she added. And then for us to come out of that trip with an agreement with the CIM to be able to work with, test and work toward doing a clinical trial was really exciting. When we first came back from Cuba from that trade mission, the world was abuzz because at that time really no one was going to Cuba.

I think for the whole world it was, 'what's going on here? I mean we did interviews from that very first trip from places all around the world. I guess the thing that I'm most proud of is that it wasn't just a flash in the pan where we got in the spotlight at the Havana airport with the governor. But we actually did something and we worked hard to be able to use this vaccine approach in a clinical trial that is ongoing.

Johnson hasnt seen the documentary, but she views it as a really intriguing story that gave Cuban doctors the respect they have sought and deserved.

When we first started talking about Cuba and this has changed the Cuban scientists and this vaccine, the arrogance that you would hear from people, she recalled. Why are they smarter than we are? They are just a third world country. How could they possibly be doing anything that's maybe better than we have? So I think it's a combination of sort of a little guy doing well that also makes this story pretty interesting.

She had a more thorough answer to why the Cuban scientists chose to partner with Roswell instead of cancer centers that are bigger, more famous or have more money.

I think the one thing that really contributed to that is Dr. Lee is a very engaging guy, she said. Youve got to look Cubans in the eye. They have to know you to trust you. And I think part of the reason we were successful is we developed a trust between our two institutions even though the politics between our two countries is very tense and sometimes controversial."

If the vaccine eventually passes the clinical trials, Johnson expects the Food and Drug Administration would approve its use in the U.S. so patients would no longer need to go to Cuba.

I know everything that we do with Cuba can be a challenge because of the relationship between our two countries, Johnson said. Were very hopeful. It seems to me it would be very difficult from the FDA's perspective, if this drug has a role, that it wouldn't be available in this country.

email: apergament@buffnews.com

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Column: Roswell Park's alliance with Cuba gets the 'wow' treatment from PBS' 'Nova' - Buffalo News

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New Delhi:A leading scientist at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in New Delhi has found that valproic acid, an anti-epilepsy drug, can be repurposed and used for acute cases of Covid-19.

The scientist, Neel Sarovar Bhavesh, has written to the director general of the Indian Council of Medical Research (ICMR), the apex body in the field, to test valproic acid at the National Institute of Virology in Pune or any ICMR lab to find a quick solution to the coronavirus crisis.

The ICGEB is part of the research consortium working to find a cure and vaccine for Covid-19.

Valproic acid is an approved drug, whose patent expired recently. It is sold under brand names such as Depacon and Stavzor to treat epilepsy. The University of California has also validated the ICGEBs research findings it lists valproic acid as one of the molecules for repurposing and testing for use against the Covid-19 virus.

Also read: AI identifies potential drugs and a DNA vaccine in the works latest on Covid-19

Bhavesh, the head of transcriptional regulation at ICGEB, told ThePrint: We have performed high-throughput virtual screening (HTVS) of 1.2 million small molecules from the four databases, and later performed Energy calculation and molecular binding simulation. We found that valproic acid CoA may be repurposed to inhibit the RNA-dependent RNA polymerase of the virus.

We have written to the DG ICMR to test this molecule on cell culture and animal testing facilities, in combination with potent binding blocking molecules. Currently no one in India outside the NIV and ICMR has access to the Covid-19 virus, Bhavesh said.

About 1,100 strains of the novel coronavirus have been sequenced from around the world. We (in India) have around 700 confirmed positive cases, but only two virus sequences are available at the NIV. These sequences are different from each other, he explained.

Bhavesh revealed that after the publication of the ICGEB research, multinational pharmaceutical company GlaxoSmithKline contacted them.

However, Bhavesh said theres an urgent need for cooperation from government bodies like the ICMR and the NIV in terms of giving researchers access to the virus strains in India to test on.

There should be synchronisation in testing and developing. If NIV or any another research institution finds success, lots of patients can be cured and saved. The need of the hour is to find the solution. The NIV must cooperate with other institutions more generously, he said.

A day before, Union Biotechnology Secretary Renu Swarup also said in an interview that early solutions for the novel coronavirus can be found from repurposed drugs, and that developing new drugs would take time.

Also read: Old drugs, new trials hopes pinned on HIV, malaria, ebola, TB vaccines to fight Covid-19

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Scientist says anti-epilepsy drug can be repurposed for Covid-19, writes to ICMR to test it - ThePrint

At least five patients, including some doctors, have overcome the critical state of health in which they had fallen due to the coronavirus and been moved from the Intensive Care units to normal hospital wards, after undergoing an expensive treatment that is producing good results.

Of the patients who have responded adequately to treatment, there are four from Santiago: Dr. Daniel Rivera, president of the Board of Directors of the Unin Mdica Clinic, urologist Fausto Hernndez, ex-governor Jos Izquierdo and patient Juan Ramn. In Santo Domingo, the political leader of San Pedro de Macors, Senator Jos Hazim, while Dr. Felix Antonio Cruz Jiminin has presented significant improvement, although he is still in intensive care with mechanical respiration, admitted to the General Hospital of the Plaza de health.

The details were offered by the Minister of Public Health, Rafael Snchez Crdenas, on the eighth day of the virtual press conference to report the updates to the Covid-19.He said it is a non-over-the-counter medicine that is applied intravenously and is applied to critically ill patients with complicated pneumonia.

A drug used in the treatment of arthritis patients has been applied to these patients.It is tocilizumab, a biological medicine, which is supplied through the High-Cost Medicines Program of the Ministry of Public Health.

Tocilizumab (Actemra) is a biologic medication approved to treat rheumatoid arthritis (RA) in adults, polyarticular juvenile rheumatoid arthritis (JRA), and the systemic form of juvenile idiopathic arthritis (JIA) in children. It isused to suppress the immune system in autoimmune diseases.

Biological drugs are artificial and manufactured using genetic engineering techniques and are closely related to a protein that the body produces naturally.

Dr. Snchez Crdenas reported that there are nine doctors registered with the virus, of whom four were in the process of their work, and others were infected on a cruise or airplane trip, and about three nurses.

He recalled that the highest risk of death is in people over 60 years old and people with co-morbidities, so he called people to take more extreme care of older adults.

Cross-testsThe Minister of Public Health, Rafael Snchez Crdenas, announced that from yesterday the trial would begin with cross-tests at the Dr. Defill National Laboratory, in order to speed up the confirmation of Covid-19 cases.

THE PROCESSSnchez Crdenas revealed that starting today, Saturday, rapid tests of up to 15 minutes will be made, through blood collection obtained from the pulpejo, with patients who have tested positive for other types of tests, to confirm their effectiveness, and then put them into service.

The testsThe effectiveness of rapid tests can be as high as 95%, and the PCR tests, which are being applied in the laboratory, are a specific test with 95% effectiveness, said Crdenas.Those 15-minute rapid tests, of which there are already samples in the country, will be tested today with patients.

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Treatment gets five out of Intensive Care - Dominican Today

Research by a University of Southern Denmark team has found that the cannabis compound cannabidiol (CBD) may act as a helper compound to boost the effectiveness of antibiotics against drug-resistant Gram-positive bacteria. A study headed by Janne Kudsk Klitgaard, PhD, associate professor, clinical microbiology, found that combining CBD with the antibiotic bacitracin (BAC) had a more powerful effect against bacteria including Staphylococcus aureus, than BAC alone. Based on these observations, the combination of CBD and BAC is suggested to be a putative novel treatment in clinical settings for treatment of infections with antibiotic-resistant Gram-positive bacteria, the researchers stated in their published paper in Scientific Reports, titled, Cannabidiol is an effective helper compound in combination with bacitracin to kill Gram-positive bacteria.

Since the discovery of penicillin by Sir Alexander Fleming in 1928, antibiotics have saved millions of lives from fatal infections worldwide, the authors wrote. However, over time, bacteria have developed mechanisms to escape the effects of one or more antibioticsmultidrug resistance (MDR)leading to an increasing global health threat. With fewer antibiotics available to treat MDR bacterial infections, the possibility of entering a pre-antibiotic era is looming ahead, the team stated.

Among alternative strategies that are being explored to help address antibiotic resistance, helper compounds, also known as antibiotic potentiators or resistant breakers, are gaining attention. Such helper compounds are non-antibiotic compounds that act as adjuvants for antibiotics, operating synergistically through mechanisms including efflux pump inhibition, enzyme inhibition, or changing membrane permeability, which can contribute to improving antibiotic efficacy.

Given that overuse of antibiotics is the main cause of antibiotic resistance, the combination of an antibiotic with a helper compound could reduce the amount of antibiotic needed to achieve bacterial growth inhibition or killing than if the antibiotic was used alone. This strategy may, therefore, decrease the likelihood of resistance development, and investigations to identify efficient helper compounds are thus important, the investigators suggested.

CBD, from the cannabis plant Cannabis sativa, acts as an antagonist of both the cannabinoid type 1 and 2 (CB1 and CB2) receptors, and has been shown to have anti-sedative, anti-psychotic, and anxiolytic effects, the team noted. The compound has also been linked with a variety of effects, including inhibiting cancer cell growth, neuroprotection in neurodegenerative diseases such as Parkinsons disease, and post-ischemia, and anti-inflammatory effects, as in type 1 diabetes.

CBD has also been observed to inhibit bacterial growth, but the use of cannabidiol as an antibiotic adjuvant hasnt yet been investigated, the team continued. Not much is known regarding antimicrobial effects of cannabinoids and even less on the mechanism of action the use of cannabidiol as an antibiotic adjuvant has not been studied so far.

For their reported study, the researchers evaluated whether CBD could act as a potential helper compound to increase the effectiveness of the antibiotic bacitracin, which is a mixture of cyclic peptides that interfere with the bacterial cell wall and interrupt biosynthesis of peptidoglycan, leading to cell lysis. The team first validated the antimicrobial effect of cannabidiol against the Gram-positive bacteria methicillin-resistant Staphylococcus aureus (MRSA), and also against Enterococcus faecalis, Listeria monocytogenes, and methicillin-resistant Staphylococcus epidermidis (MRSE). They then tested the effects of combining CBD and BAC against different Gram-positive bacteria, providing initial indication that CBD could potentiate the antimicrobial effects of the antibiotic.

Further tests with the combination of CBD and BAC against S. aureus showed that dual treatment caused morphological changes in the bacterial cells that affected cell division, so that the bacteria could no longer divide normally. the combination of CBD and BAC affects the cell envelope causing irregular cell division visualized by multiple septa formations and irregular cell membrane. These effects werent seen with either treatment on its own; CBD and BAC alone caused no morphological changes, they wrote.

The combined treatment was also found to decrease autolysis in S. aureus, while CBD was shown to cause depolarization of the cytoplasmic membrane. Gene expression analysis confirmed that treatment using CBD in combination with BAC resulted in reduced expression of key cell division and autolysis genes in the bacteria. The combination of BAC and CBD was, however, and as expected, not effective in Gram-negative bacteria. As a mixture of cyclic peptides that interrupt cell wall synthesis in Gram-positive bacteria, the antibiotic is probably unable to cross the outer membrane in Gram-negative bacteria, the researchers pointed out.

In this study, we found that the antibacterial effects of BAC against S. aureus as well as other Gram-positive bacteria can be enhanced by cannabidiol originating from the cannabis plant, the scientists concluded. They acknowledged that further work will be needed to understand the mechanisms of action of combined CBD and BAC treatment on Gram-positive bacteria. Changes observed in morphology were not caused by compositional changes in the cell wall muropeptide composition. Membrane potential changes for the combination of CBD and BAC compared to either CBD or BAC treatment alone did not reveal the mechanism of action for the combination of CBD and BAC, they wrote. Future studies are therefore focused on the cell division and cell envelope to identify the mechanism of action.

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Cannabis Compound CBD Acts as Helper to Boost Antibiotic Effectiveness - Genetic Engineering & Biotechnology News