Making the leap | C&EN Global Enterprise

November 16, 2020

https://pubs.acs.org/doi/10.1021/cen-09833-cover

https://cen.acs.org/content/cen/articles/98/i33/How-do-viruses-leap-from-animals-to-people-and-spark-pandemics.html

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So far, though, efforts to find other mutations that might power the virus’s pandemic prowess have largely fallen short. Starr, Bloom, and their colleagues set out to mutate every position in the
201-amino-acid RBD one by one and then examine how each mutation affects the protein’s folding pattern and capacity to bind ACE2. They found that the region has a high tolerance for mutations. “It can handle a high number of mutations and do its job just fine,” Starr says. The team even found dozens of mutations that boosted the RBD’s ability to bind the ACE2 receptor, but the virus seems to have not adopted any of them (Cell 2020, DOI: 10.1016/j.cell.2020.08.012). That finding suggests that the virus functions effectively with the binding affinity it has, and that there’s no strong selective pressure pushing for mutations that might increase it, Starr says. He wonders if that’s because the virus is tearing through a population that has never encountered it and has no immune defenses against it. “Right now, the virus has basically found a buffet table of susceptible [hosts].”
As the COVID-19 pandemic has progressed, one virus mutation does appear to have become a permanent feature of SARS-CoV-2’s genome. Researchers collecting virus samples from infected patients have been sequencing viral genomes and analyzing the strains spreading in different parts of the world. They have found that one mutation, a change from an aspartic acid (D614) to a glycine (G614), is now present in the majority of SARS-CoV-2 viral sequences. People infected with strains carrying this mutation tend to shed more virus than those infected with strains that don’t, hinting that this mutation may make the virus more infectious (Cell 2020, DOI:
10.1016/j.cell.2020.06.043). Farzan’s team has conducted cell studies with the lab-made viruses carrying SARS-CoV-2 spike proteins and found that the mutation causes the virus to more readily infect human cells, perhaps because there are more spike proteins on the virus’s surface (bioRxiv 2020, DOI: 10.1101/2020.06.12.148726v1). The data from those studies have not yet been peer reviewed.
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