SARS-CoV-2: natural or man-made?
Nik Petrovsky from Flinders University in Australia has been doing computer modelling of part of the surface coat of the virus - a region called the spike protein - that it uses to attach to human cells. He's also been modelling the corresponding human structure - called “ACE2” - that the spike binds to. Other animals have their own versions of ACE2 as well, but Nik’s work shows that the spike protein is much weaker at attaching to the animal versions than the human form - and he’s willing to speculate to Chris Smith about whether this is a hint the virus is manmade...
Nik - We use computer simulations which are very similar to computer programs that predict the weather, and they simulate each individual atom within a protein. And we can then use those to actually simulate the ACE2 from thirteen different species, ranging from bats to pangolins, to humans, to cats and dogs. The spike protein was predicted by our simulations to be the perfect key for the human ACE2, but not for the ACE2 from the other species; suggesting that humans were the original host.
Chris - Obviously that can't be entirely true, in the sense that this is a new virus which has obviously come from somewhere; humans don't just invent viruses in their own bodies. So where did it come from then?
Nik - One possibility that was put forward is that the virus has been circulating in humans in China, unknown, for many years. But typically we would know about that; people would be getting sick. And so then we have to look for other questions. Either it was a very rare chance event, or maybe it was designed specifically to be able to bind to human cells and infect them.
Chris - What about if we just explore the animals for a minute, because all throughout this story we've heard various suggestions: people saying it started as a bat virus, it in some way mixed with a pangolin virus and produced this perfect storm for humans. Is that not the most likely scenario here: that it's a mix and match virus that's got a few bits and pieces from various places, and by the time we're now studying it, it's just had enough time to optimise itself so it looks like a perfect fit for humans.
Nik - Well certainly that's possible, but if that was true, the virus itself and its ancestor should be able to be found in whatever animal that virus was created. In fact, the closest relative that's been found is a bat virus, which has about 96-97% similarity. Just to orientate you, the similarity between the genes in a mouse and a human is 99%. So it's definitely not a perfect match. But there's also part of the spike protein we were talking about, which is very critical to binding human cells, is actually more closely related to a pangolin coronavirus spike protein than it is to the bat. And that's where this idea... That COVID-19 had a father that was a bat virus and a mother that was a pangolin virus, and that's how it came about, as the progeny. That's certainly possible, but then we should expect to find the progeny in pangolins, which we haven't.
Chris - If it didn't then happen in a bat or a pangolin, how did it happen?
Nik - One hypothesis we haven't discussed so far is that this happened in a laboratory, where scientists routinely culture viruses and grow them. And so it's possible that you could get, if in a laboratory you were growing some bat viruses in one test tube and you were growing some pangolin viruses in another test tube, and they accidentally got mixed up in the presence of human cells, then you could create something like COVID-19 quite accidentally, even without deliberately intending to do that.
Chris - And if you did intend to do it deliberately?
Nik - We do know in some laboratories there is research going on that's called 'gain of function' research, where you deliberately try to genetically modify viruses to make them a lot more lethal, and in particular to make them more infectious to humans. And this is done to really try and predict what might be the next pandemic virus. And of course that creates enormous issues about, should you be creating a potential monster, or are you better to just wait until nature does it, and then respond to it?
Chris - And is there a smoking gun here then, that that may have happened?
Nik - We can't exclude the possibility that had happened. There's nothing scientifically that says this definitely didn't happen. We haven't yet found that wild COVID-19 ancestor, but if it was found, that would essentially say, yes, it was out there in wild animals and it crossed to humans. In terms of the laboratory hypothesis, essentially it would require an investigation of the most likely laboratories. Neither of these things are easy to do, of course.