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

A new emerging variant of SARS-CoV-2 was detected in December 2020 in Manaus (Amazonas state, Brazil). The variant belongs to a new lineage of the virus – lineage P.1, which, according to genomic analysis, descends from an earlier Brazilian variant – B.1.1.28 (detected in March 2020). The P.1 lineage carries several mutations with biological importance like the K417T, E484K, and N501Y amino acid changes on the spike. The latter had been previously 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 in a key residue of the receptor-binding domain (RBD) of the spike, known to interact directly with its human ligand – ACE2 (angiotensin-converting enzyme 2). Preliminary analysis revealed this mutation might enhance virus transmissibility, with unknowable 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. Moreover, the two emerging variants carry a mutation on position 417. But while the South African variant harbors the K417N mutation, the new variant carries a K417T change. Preliminary studies reveal that position K417 is an important target of neutralizing antibodies, suggesting that both mutations may help the virus evade vaccine-mediated and naturally acquired immunity. The set of mutations/deletions shared between the three lineages seem to have arisen independently (convergent evolution) and to spread rapidly. Current data suggests that researchers, clinicians, and policymakers should redouble virus tracking efforts and further investigate the biological consequences of these mutations.
Enhanced transmissibility is currently supported by the fast spread of this variant in Brazil, Japan, United Kingdom, among other countries. At the time of writing (January 18, 2021), over 100 genomes of the new lineage have been reported in Brazil alone, representing an abundance of 21%. In total, the new lineage P.1 carries 17 unique amino acid changes, 3 deletions, and 4 synonymous mutations.