As the world knows, we face an emerging virus threat in the Wuhan coronavirus (2019-nCoV) outbreak. The problem is, right now there are several important things that we don’t know about the situation. The mortality rate, the ease of human-human transmission, the rate of mutation of the virus (and how many strains we might be dealing with – all of these need more clarity. Unfortunately, we’ve already gone past the MERS outbreak in severity (which until now was the most recent new coronavirus to make the jump into humans). If we’re fortunate, though, we’ll still have something that will be worrisome, but not as bad as (say) the usual flu numbers (many people don’t realize that influenza kills tens of thousands of people in the US each year). The worst case, though, is something like 1918, and we really, really don’t need that.
Coronaviruses, which are rather large single-stranded RNA viruses, are nothing new in human disease. They are, in fact,
the most usual one cause of the common cold, so all of us have been infected with who-knows-how-many different coronavirus strains over the years. Generally that’s what you can expect from them: a mild, irritating respiratory infection, and in fact I’ve been fighting off just such a thing for several days now myself. Such things are generally in the upper respiratory tract, but some of these viral infections can move on to bronchitis or pneumonia, either primary (viral infection in these areas) or secondary (opportunistic bacterial infection that develops as a sequel). I had secondary bacterial pneumonia in both lungs a few winters ago, and I give the experience 0 out of 5 stars. I was extremely glad that antibiotic therapy knocked it back down so quickly (the improvement was dramatic), and I have no trouble at all picturing how pneumonia in general has managed to kill off so many people over the centuries.
All sorts of creatures have their own suite of coronaviruses infecting them, and every so often one jumps into a new species. Humans seem to be more vulnerable to viral infection from other mammals (naturally) and from birds. No one is sure what species 2019-nCoV came from, although all the evidence is that it started in a particular market in Wuhan, likely from direct blood transmission in some sort of butcher shop. The virus appears to cause a rapidly developing viral pneumonia in some patients, and the problem with that is that there is very little to be done. Supportive care is all there is to offer – as medical professionals continually remind the general public, antibiotics are useless against viruses. And although we have more actual antiviral agents than we used to, the selection in hand is not very useful against the coronaviruses. So what does biopharma research have to offer?
There is no way that a new antiviral small molecule can be discovered and developed in time to help anyone in the near future. That sounds rather pessimistic of me, but it’s true. Extremely fortunate and rapid development of such an agent would cut the lead time down to just a few years; that’s the time scale we’re looking at, and there’s no guarantee that any such drug can be found at all. No, the chances for a more rapid response come down to the biologics: a vaccine, or treatment with (say) monoclonal antibodies. (Update: here’s an overview at Biocentury on what’s going on). Extremely fortunate and rapid development of either of those would still be on the scale of many months, and if this viral outbreak is seasonal (as they tend to be) that would mean that there is nothing that’s going to arrive in time to help this season’s victims. But it also buys some time for the next round, if you want to look on the bright side.
Here’s a look at antibody therapy against MERS, to give you the idea. Manufacturing such things on scale is not trivial, but could be done. The biggest obstacle to using Mabs as therapy in this situation is their selectivity (which is also, of course, a great strength of antibodies under the right circumstances). Mutational escape is always a possibility, so ideally you’d want several antibodies at once, each targeting a different epitope and thus lowering the chance of the virus mutating its way out of the spotlight. But that makes development correspondingly more difficult.
And as this article at Science shows, vaccine development is already underway. Moderna, Inovio, and the University of Queensland are mentioned as working with the Coalition for Epidemic Preparedness Innovations (CEPI), and there are other companies who are cranking up their own efforts. It would seems quite likely that a vaccine can be developed, and the earlier work on the SARS and MERS coronaviruses will help these efforts out. But vaccines need to be tested, in animals and then in humans, and you are of course looking (as you always do with a new therapy) for safety and efficacy. You don’t want to set off nasty immune responses – the immune system is terrifying when aroused inappropriately. And you also don’t want a vaccine that the virus can evade easily by mutating some protein on its surface. A vaccine is just a way of doing endogenous antibody therapy (rather than giving a monoclonal one from outside), and the same considerations apply – raising response to several epitopes and/or known variants at the same time is the best strategy when you can manage it. Manufacturing such a vaccine on scale would be the next challenge, one that everyone involved is well aware of, and the effectiveness of a coronavirus vaccine would be partly determined by how many millions of people we would need to vaccinate.
That takes us back to the open questions about the spread of the virus. For news on this and other issues, Stat has been doing a good job rounding up the reliable information, and they’re doing it in front of their paywall. Here’s one of their latest, on the shift from trying to contain the virus to dealing with the fact that it may be too late for that strategy to work.
The signal/noise on this whole story has been suboptimal, as well it would be, so it’s important to have good sources. Vast amounts of junk information have already been circulating. For one thing, no, this particular virus was not patented in 2015, and it is not some engineered bioweapon. There are no “natural” cures or preventatives that you can buy from friendly merchants trying to sell you some. I have been forwarded clips of what are purportedly Chinese workers spraying some sort of white stuff around to supposedly block the spread of the virus, but this is also spurious – there are no virus “disinfectants” to spray around, and we’re not even sure how this virus is most likely to be spread. The best preventatives that we know of are dull stuff like avoiding getting sneezed on, not going around shaking hands with everyone, avoiding large confined crowds of people, and other basic public hygiene points. I rather doubt that face masks help much (although they certainly don’t do any harm), since we don’t know how this virus spreads and what sort of particles it might spread on. (And besides, a lot of the air that you breath while wearing one of those standard white face masks is coming from around the sides of the mask, anyway).
So that’s about as far as we can go with the information we have. A developing story, indeed, which calls for avoiding panic on one end and complacency on the other. The advent of new infectious diseases is a test of our civilization’s technological ability – let’s pass it.