In the last few days of 2019, reports started coming out of China of a mysterious “viral pneumonia” spreading through the city of Wuhan. Less than 75 days later, the World Health Organization (WHO) declared this illness, now known to be the COVID-19 coronavirus, a pandemic.
The speed at which the new coronavirus was spreading was “alarming”, the WHO said at the time. By that point, the virus had been found across nearly 60 percent of the globe, and people were desperate for answers. Conspiracy theories began to circulate that a disease this virulent could only have been man-made – rumors that were swiftly quashed by official investigations. Scientific consensus settled on a theory of zoonotic transmission, with an unfortunate horseshoe bat acting as patient zero. But the question remained: how did COVID-19 take over the planet so quickly?
A new paper, published in the Nature journal Scientific Reports, might have the answer – as well as a puzzling set of new questions. Despite the prevailing “bat” theory of the coronavirus origins, researchers at two Australian universities have found that SARS-CoV-2, the virus behind the pandemic, is better adapted to infect humans than any other species tested.
“Humans showed the strongest spike binding, consistent with the high susceptibility to the virus,” explained study co-author David Winkler, “but very surprising if an animal was the initial source of the infection in humans.”
Just like the majority of infectious diseases, COVID-19 has so far been ascribed an animal origin – most likely bats. The reason why lies in the virus genome: it is very similar to the genetic makeup of the hundreds of coronaviruses that are already known to infect bats. The main difference with SARS-CoV-2 is the “spike” protein, which the virus uses to bind itself to a specific protein, the ACE2 protein, and infiltrate the cells of the unlucky host animal.
It was this spike protein that the researchers were investigating. Taking genomic data from 13 species including bats, pangolins, and humans, as well as companion animals like cats and dogs and commercial animals such as pigs and horses, the team built sophisticated computer models of each species’ ACE2 protein receptor. They then used these models to calculate how strongly the SARS-CoV-2 spike protein could bind to them – in other words, how “easy” it would be for the virus to infect that host.
The results were surprising: “The computer modeling found the virus's ability to bind to the bat ACE2 protein was poor relative to its ability to bind human cells,” said co-author Professor Nikolai Petrovsky. “This argues against the virus being transmitted directly from bats to humans.”
“[I]f the virus has a natural source, it could only have come to humans via an intermediary species which has yet to be found,” he explained.
Strangely, one incidental finding of the research was that pangolins, one of the earlier suspected sources of the coronavirus pandemic, are more susceptible to SARS-CoV-2 than any other non-human species studied.
Pangolins were quickly dismissed as a transmission vector after it was found that the type of coronavirus found in the species was too different from SARS-CoV-2 to have been its ancestor. However, the two viruses share one important feature: an almost identical spike protein.
“This sharing of the almost identical spike protein almost certainly explains why SARS-CoV-2 binds so well to pangolin ACE2,” explained Petrovsky.
With the recent re-emergence of the so-called “lab-leak theory” of the pandemic’s origin, these findings add yet one more level of intrigue to the fiercely controversial issue.
“Pangolin and SARS-CoV-2 spike proteins may have evolved similarities through a process of convergent evolution, genetic recombination between viruses, or through genetic engineering,” noted Petrovsky. “[We have] no current way to distinguish between these possibilities.”