SARS-CoV-2 RBD of Spike protein P.1, K417T, E484K, N501Y – 484K.V2 – BR Variant

In December 2020, a new emerging variant of SARS-CoV-2 was detected in Manaus (Amazonas state, Brazil). The variant belongs to a new lineage of the virus, the P.1 lineage, which, according to genomic analysis, is descended from an earlier Brazilian variant, B.1.1.28 (detected in March 2020). The P.1 lineage carries several biologically important mutations such as amino acid changes K417T, E484K, and N501Y in the peak.

The latter had previously been identified in two other variants of the virus responsible for the COVID-19 disease, namely B.1.1.7 and B.1.351, which originated in the UK and South Africa, respectively. The N501Y change occurs at a key residue of the peak’s receptor-binding domain (RBD), known to directly interact with its human ligand – ACE2 (angiotensin-converting enzyme 2). Preliminary analysis revealed that this mutation could increase the transmissibility of the virus, with unknown consequences for mortality and morbidity rates.

The new lineage also shares an E484K mutation with the South African variant. This modification is expected to increase transmissibility and help the virus evade neutralizing immune responses. Furthermore, the two emerging variants carry a mutation at position 417. But while the South African variant harbors the K417N mutation, the new variant carries a K417T change.

Preliminary studies reveal that the K417 position is an important target for neutralizing antibodies, suggesting that both mutations may help the virus evade naturally acquired and vaccine-mediated immunity. The set of mutations/deletions shared among the three lineages appears to have arisen independently (convergent evolution) and is spreading rapidly. Current data suggests that researchers, clinicians, and policymakers should redouble virus-tracking efforts and further investigate the biological consequences of these mutations.

Currently, the improved transmissibility is supported by the rapid spread of this variant in Brazil, Japan, the United Kingdom, among other countries. At the time of writing (January 18, 2021), more than 100 genomes of the new lineage have been reported in Brazil alone, representing an abundance of 21%. In total, the new P.1 lineage carries 17 unique amino acid changes, 3 deletions, and 4 synonymous mutations.

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