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The current dominant variant of SARS-CoV-2, containing a D614G substitution in the spike protein, appears to have evolved to improve transmissibility, according to a new study in human cells and animal models. Its findings address concerns that have been raised about how this emerging mutation might improve transmissibility, antigenicity and / or pathogenesis, with implications for developing therapies. Pandemic spread of a virus in naïve populations can select mutations that alter pathogenesis, virulence and / or transmissibility. The mutations could challenge the development of therapeutic vaccines and antibodies. Today, the ancestral form of SARS-CoV-2 that emerged from China has been largely replaced by strains containing a D614G mutation in the virus peak. Although this peak substitution is prevalent in global SARS-CoV-2 strains, its effects on viral pathogenesis and transmissibility remain unclear. To understand them better, Yixuan Hou, Ralph Baric and colleagues engineered a SARS-CoV-2 variant containing this substitution and used it to compare, in a series of experiments on human cells and animal models, the characteristics of the new variant against the ancestral one form. Compared to the ancestral virus, the variant showed a greater ability to infect upper airway epithelial cells and to replicate, demonstrated work on human cells. In Syrian mice and hamsters designed to exhibit human cellular characteristics, both viruses produced similar viral titers in respiratory tissues; hamsters showed increased weight loss, suggesting a marginal impact on disease outcomes from the variant, the authors say, but overall, the findings suggest that D614G substitution does not significantly improve virus pathogenesis. The variant spread much faster in hamsters, the authors say. So, they say, the virus appears to have evolved not from greater pathogenicity, but from greater transmissibility in humans. They also assessed the neutralization properties of convalescent human serum samples and SARS-CoV-2 neutralizing monoclonal antibodies on the variant and ancestral form, finding no significant differences. These data suggest that current vaccination approaches targeting the ancestral spike protein should be effective against D614G strains, the authors say. They note several limitations of their study and point out: “It is clearly important to monitor and identify the emergence of new variants of SARS-CoV-2.”
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