SARS-CoV-2 Variants

Several variants of SARS-CoV-2 emerged between July and December 2020. Four of these were reported to carry mutations on the spike protein with a predicted impact on the epidemiology of the COVID-19 disease. These variants were first reported in the UK (lineage B.1.1.7 or VUI202012/01), South Africa (lineage B.1.351 or 501Y.V2), Brazil (lineage P.1 or 484K.V2), and more recently in California, US (lineage GH/452R.V1 or CAL.20C), New York, US (lineage B.1.526) and in India (lineage B.1.617 or G/452R.R3). Variants first identified in the UK, SA, and BR all share an important amino acid change in the receptor-binding domain (RBD) – mutation N501Y. This mutation is predicted to increase the spike’s binding affinity towards the human ACE2 receptor, suggesting enhanced human-to-human transmissibility in comparison to earlier variants of the virus. Besides these mutations, variants SA and BR share two additional mutations in this region – mutation E848K and K417N/T. The first is suspected to contribute to further increase binding affinity to ACE2; the second is predicted to enhance SARS-CoV-2 ability to escape the immune response. Surprisingly, these mutations appear to have emerged by a process of convergent evolution, as lineages were found to be phylogenetically distant from each other. Plus, the UK variant carries another mutation with a predicted impact on transmissibility outside the RBD – deletion H69/V70. The deletion has been detected before in mink-associated strain found in Denmark, but the combination of the deletion and mutation N501Y was only reported for the first time on the B.1.1.7 lineage. The Californian variant emerged much later than the previous variants. Despite being detected very early (July 2020), its frequency only began escalating in January 2021. CAL.20C carries a distinct mutation in its RBD – mutation L452R - a mutation shared with the variant first reported in India. Its impact on COVID-19 transmissibility is still unknown; however, prior studies have revealed that this change might enhance SARS-CoV-2 immune evasion ability. Additionally, the Indian variant carries a E484Q mutation (similar to the E484K mutation found in the UK and SA), which might have a similar influence on the infectivity of SARS-CoV-2. Preliminary studies revealed some vaccines might see their efficacies reduced against these variants. However, more studies are necessary to fully grasp the biological significance of these changes as well as their impact on the severity of the COVID-19 disease.
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