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Scientists across the world are closely tracking the spread of mutations in the coronavirus and investigating whether they could render current vaccines less effective. SARS-CoV-2 is no Ferrari among viruses when it comes to mutations. Scientists reckon that its 30,000-base RNA genome acquires around two single-letter mutations a month, a rate around half as fast as influenza and one-quarter the rate of HIV. But allowed to multiply and jump from body to body for more than a year, SARS-CoV-2 has inevitably flourished into a genetically diverse tree branching into countless different variants. Many variants—defined by a specific assortment of mutations—are relatively unremarkable. But scientists have been keeping a close watch on three rapidly spreading variants—first identified in the UK, South Africa, and Brazil—which harbor an unusual constellation of mutations. They all share a mutation called N501Y that affects the receptor binding domain (RBD) of the spike protein, which the virus uses to clasp onto human cells’ receptors and enter them. That mutation replaces SARS-CoV-2’s 501st amino acid, asparagine, with tyrosine, potentially allowing it to bind more tightly to ACE2 receptors, studies in cells and animal models suggest. By itself, that mutation isn’t unusual, but the variants possess an exceptionally large number of other mutations, some also on the spike protein. Substantive changes to a virus’ behavior, such as heightened transmissibility, are likely the result of multiple mutations rather than individual ones, molecular epidemiologist Emma Hodcroft of the University of Bern tells The Atlantic. The observation that similar mutations have appeared in three independent variants, and the fact that they are spreading, makes scientists suspect that they may have an evolutionary edge. “They have multiple, eight to ten, mutations in the spike protein all stacked up at once—that suggests that there [is] a lot of evolution and adaption of the protein happening,” Daniel Jones, a molecular pathologist at the Ohio State University, tells The Scientist. “The concern being that since that’s the target of vaccinations and . . . the target for antibody [therapies] like the Regeneron cocktail, for instance, that it might be the beginning of a virus that could evade antibody therapy and/or vaccine coverage.”
SARS-CoV-2 mutations’ effects on transmissibility
It’s often in a virus’ interest to become more transmissible so it can spread and replicate more quickly. Earlier in the pandemic, a spike protein mutation known as D614G—which is widely believed to have made the virus more transmissible—surged to dominance around the world, notes virologist John Moore of Weill Cornell Medical College. Epidemiological data suggest that the B.1.1.7 variant, a descendant of the D614G lineage first identified in the UK that has spread to other parts of the world, also has heightened transmissibility. Eight of the 17 mutations it has recently accumulated are in the spike protein, which could feasibly have an effect on ACE2 binding and virus replication. Hypothetically, if a virus can bind more tightly to the body’s ACE2 receptors, it could be more capable of establishing an infection once it gets into the body and/or of generating more viral particles in the upper respiratory tract, making it easier to transmit to other people, particularly during the presymptomatic stage, explains Theodora Hatziioannou, a virologist at the Rockefeller University in New York. She adds that in her view, it’s hard to definitively ascribe case surges, including the current one in the UK, to single factors such as increased transmissibility, over other driving factors, such as what she sees as ineffective lockdown policies. “I’m not saying that [increased] transmissibility is out of the question. I’m just saying it’s extremely hard to prove.” In South Africa, epidemiologists have estimated that the new variant there, B.1.351 (also known as 501Y.V2), is around 50 percent more contagious compared with dominant lineages, based on its rapid spread, according to The Wall Street Journal. In Brazil, it’s too early to conclude whether a variant now circulating there, called P.1, is inherently more transmissible. First reported on January 12 in the state of Amazonas, it’s been associated with a devastating surge in cases in Manaus, a city where researchers had previously estimated that 75 percent of residents had already been infected with SARS-CoV-2. But it’s still unclear whether properties of the virus itself are contributing to the surge, says virologist Paola Resende of the Oswaldo Cruz Institute in Rio de Janeiro. “In Brazil, we can see a lot of parties, we can see the pubs crowded, and people are on the streets not wearing masks. I think this behavior of the population is the main reason [for] the increase.”
Evading the immune system
Our immune system—and, in particular, antibodies—is a powerful evolutionary force on viruses. Some pathogens such as influenza, and maybe also common cold-causing coronaviruses, mutate their proteins toward new shapes to avoid being targeted by antibodies that would normally prevent them from infecting cells, a process known as antigenic drift. A study recently posted as a preprint to bioRxiv by Hatziioannou and her colleagues suggests that the RBD mutations present in the B.1.351 variant are due to antigenic drift. The team passaged a model virus bearing the dominant SARS-CoV-2 spike protein in the presence of individual neutralizing antibodies extracted from people who had received either the Moderna or Pfizer/BioNTech vaccine. Depending on which antibody they were cultured with, the viruses would gradually adopt a single mutation—either E484K, K417N, and N501Y—which are present in B.1.351. That suggests that “the virus is mutating in these positions to avoid antibodies,” Hatziioannou says. Such antibody-escape mutations don’t necessarily mean that the virus will cause more severe disease or entirely outwit the immune response, she cautions. There are other parts of the immune system to help clear the virus. There’s no evidence so far to suggest that the variants identified in South Africa or Brazil are more lethal. Based on an analysis of several datasets, scientists in the UK suggested last week there’s a “realistic possibility” that B.1.1.7 is deadlier than previous strains, but experts say it’s still too early to draw that conclusion. Another concern is about whether people who have overcome mild infections with older variants could become reinfected with a new one. Nobody that I know has been losing a moment of sleep over the UK variant from a vaccine-efficacy perspective.....
Via Juan Lama
