Key mutations in Alpha variant enable SARS-CoV-2 to overcome evolutionary weak points

Transmission electron micrograph of SARS virus particles isolated from a patient. Image taken at the NIAID Integrated Research Facility, (IRF), Fort Detrick Maryland. Color-enhanced. Credit: NIAIDA key mutation in the "Alpha variant" of SARS-CoV-2 is the deletion of two amino acid H69/V70. This allows the virus to overcome weaknesses as it evolves, according to an international team.SARS-CoV-2, a coronavirus is named after the spike proteins that are found on its surface. This gives it the appearance of a crown (or 'corona'). The spike proteins bind with ACE2, a protein receptor that is found on the cells' surfaces. The spike protein and ACE2 then get cleaved. This allows genetic material from virus to enter host cells. To allow the virus' replication and spread, the virus modifies the machinery of the host cell.SARS-CoV-2 multiplies and divides, which causes genetic errors that cause it to evolve. Some mutations make it more transmissible, others make it more infectious. Others help it evade immune responses, making vaccines less effective.Cambridge scientists noticed that SARS-CoV-2 mutations were occurring in the case of an immunocompromised person who was being treated with convalescent blood plasma. They noticed a crucial mutation, the deletion of H69/V70 amino acids in spike protein. This mutation was later discovered in B1.1.7, which is the variant that led the UK to be placed under strict lockdown again in December (now known as the 'Alpha variation').Researchers have now published research in Cell Reports that shows the H69/V70 deletion is found in over 600,000 SARS/CoV-2 genome sequences. This has led to global expansion in Europe, Africa, and Asia.The research was conducted by scientists from the University of Cambridge, MRC University of Glasgow Centre for Virus Research and The Pirbright Institute. The MRC Laboratory of Molecular Biology and Vir Biotechnology were also involved in the project.The study's senior author, Professor Ravi Gupta, from the Cambridge Institute of Therapeutic Imology and Infectious Disease, University of Cambridge, stated: "Although this mutation was first seen in an immunocompromised patient, and then in the Kentnow Alpha' - variant, but when we looked at samples taken from all over the world, it became apparent that this mutation has been spread independently multiple times."Professor Gupta worked under controlled conditions with his colleagues to create a pseudotype virus - a virus that exhibits SARS-CoV-2 spike protein with the H69/V70 deletion. This virus is harmless and can be used to understand how spike protein interacts and interacts with host cells.They tested the virus against blood sera from 15 people who had been infected. The virus did not 'escape' any neutralising antibodies that were made after vaccination or previous infection. The team discovered that the virus is twice as infective, that is, it can penetrate the cells of the host. This was in contrast to the global epidemics that occurred during the second half 2020. The reason for this was that virus particles with the deletion contained more mature spike proteins. This allows the virus's ability to replicate quickly even if it has other mutations.Professor Gupta stated that viruses can acquire mutations to enable them to reproduce. This could affect their ability to replicate."What we observed with H69/V70 was that the deletion allowed the virus to compensate for other mutations that caused the virus to escape immune response. These variants were able to escape immunity better and be more infectious thanks to the deletion.Dr. Dalan Bailey, from The Pirbright Institute who led the research, said: "In evolutionary terms when a virus develops weakness it can lead it to its demise. But the H69/V70 deletion indicates that the virus can mutate further than usual. These deletions are likely to be why they are so common.Bo Meng, first author of the paper from the Department of Medicine, University of Cambridge, stated: "Understanding key mutations is important because this allows us to predict how a variant might behave in humans once it is identified." This allows us to implement early public health and containment strategies.Further Structural Changes in the SARS-CoV-2 Alpha, Beta and Variants IdentifiedMore information: Bo Meng et al., Recurrent emergence SARS-CoV-2 deletion H69/V70, and its role in Alpha variant B.1.1.7 Cell Reports (2021). Information from Cell Reports: Bo Meng et al., Recurrent emergence SARS-CoV-2 deletion H69/V70, and its role in Alpha variant B.1.1.7. (2021). DOI: 10.1016/j.celrep.2021.109292