SARS-CoV-2 jumped from bats to humans without much change

How much does SARS-CoV-2 need to change to adapt to its new human host? In a research article published in the open access journal PLOS Biology Oscar MacLean, Spyros Lytras from the University of Glasgow, and colleagues, show that since December 2019 and during the first 11 months of the SARS-CoV-2 pandemic there has been very little “major” genetic change seen in hundreds of thousands of virus genomes sequenced.

The study is a collaboration between researchers from the United Kingdom, United States and Belgium. Lead authors Prof David L Robertson (at the MRC-University of Glasgow Center for Virus Research, Scotland) and Prof Sergei Pond (at the Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia) were able to transform their data analysis experience from HIV and other viruses for SARS-CoV-2. Pond’s state-of-the-art analytical framework, HyPhy, was instrumental in discovering the evolution signatures embedded in the virus genomes and is based on decades of theoretical knowledge about molecular evolutionary processes.

The first author, Dr. Oscar MacLean, explains: “This does not mean that no changes have occurred, mutations without evolutionary significance accumulate and ‘surf’ over the millions of transmission events, as they do in all viruses.” Some changes can have an effect; for example, the Spike D614G replacement that was discovered to increase transmissibility and some other adjustments in the biology of the virus spread throughout its genome. Overall, however, “neutral” evolutionary processes dominated. MacLean adds: “This stasis can be attributed to the highly susceptible nature of the human population to this new pathogen, with limited pressure on the population’s immunity and lack of restraint, leading to exponential growth, making almost all viruses winning.”

Pond comments, “What has been so surprising is how transmissible SARS-CoV-2 has been since the beginning. Normally, viruses that jump into a new host species take time to acquire adaptations to be as capable of spreading as SARS-CoV-2, and most never make it past that stage, resulting in dead ends or localized outbreaks. “

Studying the mutational processes of SARS-CoV-2 and related sarbecoviruses (the group of SARS-CoV-2 viruses belongs to bats and pangolines), the authors found evidence of quite significant changes, but all before the emergence of SARS-CoV-2 in humans. This means that the “generalist” nature of many coronaviruses and their apparent ease of jumping between hosts, imbued SARS-CoV-2 with the ready ability to infect humans and other mammals, but these properties probably evolved in bats before overflowing to the humans.

Co-first author and Ph.D. student Spyros Lytras adds: “Interestingly, one of the nearest bat viruses, RmYN02, has an intriguing genomic structure composed of segments similar to SARS-CoV-2 and the bat virus. Its genetic material carries distinct composition signatures (associated with the action of the host’s antiviral immunity), supporting this change in the evolutionary rhythm that occurred in bats without the need for an intermediate animal species ”.

Robertson comments, “the reason for SARS-CoV-2 ‘shifting’ in terms of its higher rate of evolution in late 2020, associated with more strongly mutated strains, is because the immune profile of the human population has changed.” By the end of 2020, the virus was increasingly coming into contact with the host’s existing immunity, since the number of people previously infected is now high. This will select the variants that can avoid part of the host’s response. Along with the evasion of immunity in long-term infections in chronic cases (for example, in immunocompromised patients), these new selective pressures are increasing the number of important mutant viruses.

It is important to recognize that SARS-CoV-2 still remains an acute virus, eliminated by the immune response in the vast majority of infections. However, it is now moving away faster from the January 2020 variant used in all current vaccines to boost protective immunity. Current vaccines will continue to work against most circulating variants, but the more time that passes and the greater the gap between the number of vaccinated and unvaccinated people, the more opportunity there will be for the vaccine to escape. Robertson adds: “The first race was to develop a vaccine. The race now is to get the global population to be vaccinated as soon as possible.”