Transmission electron micrograph of SARS-CoV-2 virus particles isolated from a patient. Image acquisition and color enhancement at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Image Credit: NIAID
With the highly infectious SARS-CoV-2 variant B.1.351, which recently appeared in South Africa, scientists are wondering how existing COVID-19 vaccines and therapies can be improved to ensure strong protection. Researchers who report on ACS in the Journal of Medicinal Chemistry have used computer models to find that one of the three mutations that distinguish variant B.1.351 from the original SARS-CoV-2 reduces the binding of the virus to human cells – but possibly enables it allow him to escape some antibodies.
Since the original SARS-CoV-2 was first discovered in late 2019, several new variants have emerged, including those from Great Britain, South Africa and Brazil. Because the new variants appear to be more transmissible and therefore spreading rapidly, many people fear that they could undermine current vaccines, antibody therapies, or natural immunity. Variant B.1.351 carries two mutations (N501Y and E484K) that can improve the binding between the receptor binding domain (RBD) of the coronavirus spike protein and the human ACE2 receptor. The third mutation (K417N; a mutation from lysine to asparagine at position 417) is puzzling because it eliminates a beneficial interaction between RBD and ACE2. As a result, IBM Research’s Binquan Luan and Tien Huynh wanted to investigate possible benefits of the K417N mutation that could cause the coronavirus to develop that way.
The researchers used molecular dynamics simulations to analyze the consequences of the K417N mutation in variant B.1.351. First, they modeled the bond between the original SARS-CoV-2-RBD and ACE2 and between the RBD and CB6, a SARS-CoV-2 neutralizing antibody that was isolated from a recovered COVID-19 patient. They found that the original amino acid, a lysine, at position 417 in the RBD interacted more strongly with CB6 than with ACE2, which is consistent with the therapeutic efficacy of the antibody in animal models. The team then modeled the bond with the K417N variant, which converts this lysine into asparagine. Although this mutation decreased the strength of the binding between RBD and ACE2, it decreased the binding of the RBD to CB6 and several other human antibodies to a much greater extent. Thus variant B.1.351 seems to have sacrificed a close bond to ACE2 at this point in order to be able to evade the immune system. This information could prove useful to scientists as they work to improve protection for current vaccines and therapies, the researchers say.
How British and South African Coronavirus Variants Escape Immunity
Binquan Luan et al. Insights into SARS-CoV-2 Mutations to Avoid Human Antibodies: Sacrifice and Survival, Journal of Medicinal Chemistry (2021). DOI: 10.1021 / acs.jmedchem.1c00311 Provided by the American Chemical Society
Quote: How a SARS-CoV-2 variant sacrifices the close bond for antibody evasion (2021, April 28), accessed on April 28, 2021 from https://medicalxpress.com/news/2021-04-sars-cov- variant-sacrifices-tight-antibody.html
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