A Duke-led research team has discovered how multiple mutations in the SARS-CoV-2 spike proteins can create variants that may be more transmissible or resistant to antibodies. This was done by combining computation and structural biology.One variant of the spike protein can leap from humans to minks by acquiring mutations. Others variants, including Alpha, first discovered in the United Kingdom, Beta in South Africa and Gamma first found in Brazil, also developed spike mutations that increased their ability to spread quickly in human populations and resist certain antibodies.Science published the findings of these researchers.Priyamvada Acharya (Ph.D.), senior author and director of the Division of Structural Biology, Duke Human Vaccine Institute, stated that the spike at the virus's surface allows SARS-CoV-2 to enter host cells.Acharya stated that changes in the spike protein are what determine the transmissibility of virus. This is how it spreads and how quickly. "Some variants of the SARS CoV-2 spike occur at different times and in different locations around the globe, but they have similar results. It is important that we understand the mechanisms of these spike mutations, as we fight this pandemic.Acharya, along with her colleagues, including Sophie Gobeil (Ph.D.) and Rory Henderson (Ph.D.), developed structural models to identify modifications in the spike protein of the virus. Cryo-electron microscopic allowed for atomic level visualization. Binding assays enabled the team create live viruses that were directly related to their function in host cells. The team then used computational analysis to create models that demonstrated the structural mechanisms in action.Henderson stated, "By creating a skeleton for the spike, it was possible to see how the spike moves, and how that movement changes with mutations." Although the different spike variants do not move in the same manner, they all accomplish the same task. Although the different variant spikes do not move in the same manner, they accomplish the same task. Variants that first appeared in South Africa and Brazil used one mechanism while those found in the UK and mink variants use a different mechanism.All variants had an increased ability to bind with the host, notably through the ACE2 receptor. These changes created viruses that were more resistant to antibodies. This raises concerns about the effectiveness of existing vaccines.Gobeil stated that the research revealed the complexity of the virus. "It's incredible how many ways the virus can be more infectious or invasive," she said. Nature is smart.Apart from Gobeil and Acharya, Henderson, the study authors are Katarzyna Janowska and Shana McDowell.The National Institutes of Health supported the study (R01 AI145687,AI142596) as well as the State of North Carolina through CARES Act.
