The race to find the coronavirus cure – British GQ

We all know, by now, what it looks like. A sphere, some 120 nanometres in diameter, hedgehogged by what appear to be microscopic Nik Naks, the most famous positive-sense single-stranded RNA virus in history.

We think we know where it came from likely a Wuhan wet market, where live animals of all stripes are stored and slaughtered in close quarters. And we know the likely candidates maybe a bat, possibly a pangolin. We know its zoonotic, which is to say it went from them to us.

And we know, of course, what it does once it gets there: once in the lungs' mucus, those Nik Nak protrusions will get incredibly lucky, because once it bumps into one of the cells that line the lung wall it will find, protruding from the cells surface, a chunk of protein, which normally helps modulate hormones within the body, but whose shape matches the virus protrusions so perfectly they stick together. The cells will fuse and the RNA payload of the virus will be deployed.

We know that some people wont have symptoms at all, unwitting members of the virus shadow-spreader army. And we know for others that it starts with a persistent cough and then a fever. For most, we know that means a week, maybe two, in bed. But we know that for others, as the virus is copied over and over again by our own ribosomal proteins, that each breath will feel like a battle: we know they may need medical help, they may need a ventilator and we know that for some, no amount of help will be enough.

We know it hardly affects children, though we dont know why. We know it affects the old much more severely, though we dont understand the disparity. We know that if youre relatively young and healthy and dont smoke and exercise regularly your symptoms will be mild. Or, rather, we thought we knew. That was last week. Now we know its far more egalitarian than we ever suspected.

And yet, for a virus currently spreading across the globe at pandemic speed, taking the lives of thousands and threatening the lives of millions, we actually do know an incredible amount.

Just as the Chinese government were looking to quarantine the entire city of Wuhan in mid-January, the country's scientists had already identified the virus one that would officially be named sars-cov-2; Covid-19 is the disease it creates in humans and shared its genetic sequence with scientists all over the world. The race was on.

All vaccines, points out Professor Paul Klenerman, a specialist in virology at Oxford University, essentially do the same thing: They introduce some component of the virus so that the immune system can recognise it, so when it sees the real thing it's already got that memory.

The old-school approach would have seen a weakened version of the virus this involves growing it in culture until its attenuated introduced. Its how we came up with a vaccine for yellow fever. It can produce good protection, but its slow.

And yet, with sars-cov-2, there are problems. Even a weakened novel virus could make a patient significantly sick and weakening it in the first place is difficult.

So, new virus, new rules: the World Health Organization currently lists more than 40 companies and institutions around the world all working on a cure at breakneck speed, with only a couple using anything similar to this method.

But while the advanced techniques are elegant such as a method that essentially gives your body instructions on how to create the perfect antibodies without any version of the virus ever being introduced all vaccines have some old-school bottlenecks, such as animal and human testing, along with mass production.

And while at a meeting of the WHO in mid-February it was agreed that, for the first time, human testing could start before animal testing had ended, the reality is it will take a year to develop, even with the most optimistic estimate, with anything up to two years likely.

One of the quickest ways to get a vaccine to market is to use a vector vaccine that essentially uses another virus to deliver a piece of the problematic virus to the immune system. In the case of theOxford Universityteam, theyre delivering the genetic sequence of the spike protein that latches onto the lung cells.

Its about using a platform that is already quite tried and tested, says Klenerman. You know the vector can accept enough antigen from the viral information. You know it produces a good enough immune response. You basically know its safe, because the safety of the vaccine really depends on the vector.

The Oxford team will be using an adenovirus it originally comes from chimpanzees which has been tested endlessly in studies of infectious diseases and cancers as a suitable genetic smuggler. The team has also already done several trials with Middle East respiratory syndrome (mers) using the same technique and with significant success.

So we already know quite a lot about what sorts of immune responses can be generated against that sort of protein, says Klenerman.

And theyre not the only ones.The German Centre For Infection Researchare looking to use measles as the vector, researchers at theUniversity Of Hong Kongare using a weakened fly virus, whileJohnson & Johnsonin the States are using a virus that causes the common cold.

Animal trials of the Oxford vaccine will start next month on ferrets and macaques, with the team hopeful of the first human trials in the summer.

Yet even with the shortened testing and manufacturing periods that a known vector vaccine would allow, Klenerman says around a year is the most optimistic timeframe for it to arrive.

You cant shortcut this too much, he says. You need the data. Itll take many months of trialling. Everyone is really cautious about introducing a vaccine thats safe, that doesnt cause any harm.

When Stphane Bancel, the chief executive of a small Boston biotech groupModernathat, after almost a decade, had still yet to turn a profit, called a colleague at the National Instututes Of Health last autumn, the idea was for the two organisations to run a test at the companys manufacturing plant to see how swiftly they could respond to a potential pandemic. But before that test was even possible, the real world intervened.

Moderna has moved with breakneck speed. From receiving the virus entire genetic sequence on 10 January, its 40 scientists managed to develop a vaccine in what is a world record from identification to potential cure: just 42 days. And just two weeks ago, on 16 March, Neil Browning a 46-year-old software engineer at Microsoft became the second human test subject, after being injected with a substance Moderna is calling mRNA-1273 as early clinical testing began, making it total of 63 days from sequencing to injection.

Its overwhelmingly the world record, said Anthony Fauci, the director of the National Institute Of Allergy And Infectious Diseases. In total, 45 subjects are set to receive the test vaccine in the coming weeks.

The speed is due to the ground-breaking area of viral genetics, whereby scientists can work on the vaccine after receiving its genetic sequence by email, without the need for a sample of the virus itself. Human cells are then genetically reprogrammed for the production of the coronavirus protein. Essentially, the body creates something that looks like the virus and so can learn how to fight it in a way that is entirely safe: a punching bag instead of a puncher. You essentially bypass the virus bit, says Klenerman.

But its very cutting-edge techniques may prove to be the problem. Its an elegant solution when modelled on a computer, but while these things sometimes work quite well in preclinical models, adds Klenerman, theyre not quite so powerful in humans. There are also question marks over how quickly production could be scaled up.

Another American company Inovio are using the same technology, as areCureVacin Germany. The latter sparked international headlines last month when it was reported that the Trump administration offered the company large sums of money for exclusive rights to any Covid-19 vaccine they developed.

Germany is not for sale, German economy minister Peter Altmaier told broadcaster ARD in reaction to the news.

Currently, no vaccine made from genetic material has ever been approved for use and even the most optimistic estimates put a vaccine coming from this technique at 18 months away.

Perhaps the biggest irony of most modern vaccines is that so few have been put into widespread use, coming as they often do so long after the initial outbreak, by which time its often been contained or people have developed immunity (or, rather, the survivors have). This is what happened with many severe acute respiratory syndrome (sars) and ebola vaccines funding vanished when the panic subsided.

There is always that potential, says Klenerman. Hopefully these will be quick enough that youll be able to see if they work or not.

In the short- and medium-term, the only hope is existing drugs ones already approved for other purposes or already known to be largely safe. These wont make you immune, but can be administered to diagnosed patients and may end up saving many more lives than a vaccine arriving when the damage has already been done.

Earlier this month the World Health Organization launched Solidarity, a global megatrial of the four most promising treatments.

The most hopeful of these is Remdesivir. Originally designed to combat ebola, it shuts down viral reception by inhibiting a key viral enzyme. The only problem was, it didnt work on ebola. Yet later lab and animals studies showed that it did prove effective on both sars and mars two incredibly close relations to sars-cov-2. In fact, the very first patient in the States with Covid-19 was given it when his condition worsened and improved the next day. It can also be given at high doses without risk of toxicalities.

Jiang Shibo of Fudan University, an expert in coronavirus therapeutics, has said that Remdesivir has the best potential to be used in clinics.

Creator Gilead Sciences recently courted controversy after applying and being granted orphan drug status for Remdesivir, meaning years of exclusivity and the ability to set whatever price it sees fit. Gilead Sciences later asked the FDA to rescind the status after a public backlash, with presidential candidate Bernie Sanders calling the move truly outrageous.

WHO was all set to exclude another compound chloroquine and hydroxychloroquine from its global megastudy, but changed its mind in mid-March as the drugs received significant attention in many countries. It was curious, as it seemed the least promising of the bunch.

One person who has certainly had their attention on it is the American president Donald Trump, who has repeatedly talked up the medication, calling it a game changer. In fact, he has talked it up so much that people have taken the non-medical version of chloroquine chloroquine phosphate, a chemical used to clean fish tanks in apparent attempts to self-medicate, with several ending up in emergency rooms as a result and one man from Arizona dying.

And yet its hard to understand what Trump sees in it. The decades-old antimalarial which works by decreasing the ability of the virus cells to ingest other cells has been used in trials against two other viral diseases (dengue and chikungunya) without success, while no evidence suggests it works with Covid-19 either.

One of the main mysteries that remain, says Klenerman, is why some people develop mild symptoms, while for others it's severe. It is, he says, currently a big, big area of research to try to understand what process is happening in the patients that leads them to develop severe disease, whereas some people will have a mild or even a completely asymptomatic course.

Right now, there are advanced technologies that can pick apart our immune responses against the virus piece by piece, cell by cell, molecule by molecule, with the hope of understanding it. The solution may be a medication we already have. I just hope we make some progress very quickly.

How to take control of your coronavirus anxiety

Best hand sanitiser and hand soap to keep bacteria at bay

How I passed the time in coronavirus-related self-isolation

Read more:
The race to find the coronavirus cure - British GQ