Angela L. Rasmussen and Stephen A. Goldstein write:

In March 2020, a group of renowned evolutionary virologists analyzed the genome sequence of SARS-CoV-2 and found it was overwhelmingly likely that this virus had never been manipulated in any laboratory. Like the earlier coronaviruses SARS-CoV and MERS-CoV, they theorized, it “spilled over” from its natural reservoir host (bats) to a new one (humans). Viruses jump species frequently, with unpredictable consequences. Often a virus hits an evolutionary dead end if it cannot adapt to the new host rapidly enough to be transmitted again. Sometimes, however, it can. Clues that reveal this scenario can be found by analyzing the sequence of the virus genome, and that’s exactly what this study did.

The study carefully examined whether key elements of the virus, particularly the spike protein on its surface, appeared engineered. They did not. The spike didn’t optimally bind to its receptor, ACE-2, and the interaction between the two proteins was unpredictable even using the most advanced computer algorithms. Another key feature often cited as evidence of laboratory origin is the furin cleavage site, where the spike protein is cut in half to “activate” viral material for entry into cells. The viruses most closely related to SARS-CoV-2 don’t have this site, but many others do, including other human coronaviruses. The furin site of SARS-CoV-2 has odd features that no human would design. Its sequence is suboptimal, meaning its cleavage by the enzyme furin is relatively inefficient. Any skilled virologist hoping to give a virus new properties this way would insert a furin site known to be more efficient. The SARS-CoV-2 site has more of the hallmarks of sloppy natural evolution than a human hand. Indeed, a timely analysis last year showed convincingly that it is a product of genetic recombination, a natural feature of coronavirus replication and evolution.

Unfortunately, the pandemic has provided many opportunities to observe SARS-CoV-2 evolution in humans as it unfolds — and confidence in its natural origin has grown over time. The molecular handshake between SARS-CoV-2 and ACE-2, seemingly unique in early 2020, turns out to be found in several related viruses and has since evolved to be a better fit. Its ability to infect human cells also turns out to be unremarkable. A related virus discovered in pangolins infects human cells even more readily than SARS-CoV-2. The virus behind the pandemic may be special in its impact on our lives and the global economy, but the way it infects us isn’t unique at all.

The evolutionary trajectory of SARS-CoV-2 further undermines claims that the virus is obviously artificial and designed for human transmission. Early in the pandemic, a mutation called D614G took hold and spread rapidly around the world, showing that the virus was adapting to its host from the very beginning. Since then, mutations in the region of the spike protein that binds ACE-2, as well as near the furin cleavage site, show continued adaptation. Several of these are found repeatedly in different variants of concern and almost certainly contribute to increased transmissibility. SARS-CoV-2 continues to evolve. It wasn’t perfectly tuned for humans when it appeared, just good enough. [Continue reading…]