An international team of scientists has identified one of the most important mutations in the SARS-CoV-2 "Alpha variant". It is the deletion of H69/V70 amino acids. This allows the virus to overcome any weaknesses in its armor as it evolves.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, and genetic errors cause it to mutate. 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 patient who was receiving convalescent plasma. They noticed a crucial mutation, the deletion of H69/V70 amino acids in spike protein. This was later discovered in B1.1.7, which is the variant that led the UK to be forced into another tight lockdown 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 at the University of Cambridge, stated: "Although this mutation was first seen in an immunocompromised patient, then in the Kent variant - now referred to as 'Alpha' – variant, but when we looked at samples taken from all over the world, we found 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 is harmless and displays the SARS-CoV-2 spike proteins and the H69/V70 deletion. This virus was used to study how spike proteins interact with host cells and why this mutation is so important.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 break into host cells, as the global epidemic of global infections that occurred in 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 reproduce."What we observed with H69/V70 was that the virus could compensate for other mutations that allowed it to escape the immune system. 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 is able mutate more than it would otherwise." 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.###Wellcome, Bill & Melinda Gates Foundation, and the National Institute for Health Research, (NIHR), Cambridge Biomedical Research Centre supported the research.Refer toMeng, B. Kemp, SA. Papa, G. Datir R. Ferreira, IATM, et al. Recurrent emergence SARS-CoV-2 spike deletion (H69/V70) and its role 1 within the variant of concern Lineage B.1.1.7. Cell Reports; 8 Jun 2021; DOI 10.1016/j.celrep.2021.109292
