Inactivated SARS-CoV-2 Variant Gamma, Lineage P1 (Japan/TY7-503/2021)

During the second wave of the COVID-19 pandemic in Brazil, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) P.1 (Gamma) lineage accounted for the vast majority of genomes sequenced. It is considered one of the most relevant "variants of concern" (VOCs) globally. It harbors 10 nonsynonymous mutations in its spike protein, three of which are located in the receptor binding domain (RBD): K417T, N501Y, and E484K. Notably, N501Y has been shown to enhance affinity for ACE-2 binding, potentially leading to higher viral loads.

Researchers have demonstrated that the E484K substitution has emerged and been maintained in four genetically diverse lineages in Brazil. It can induce immune escape, leading to reinfection, and is associated with failure of convalescent plasma therapy. K417T is located at a site important for class I anti-RBD antibodies and is thought to be associated with reduced neutralizing activity of some monoclonal antibodies (mAbs). Despite the predominance of spike mutations, P.1 viruses also harbor substitutions at other potentially relevant sites. Mutations in nonstructural proteins may alter their functions related to transcription, replication, and immune regulation. Indeed, studies suggest that at least emerging viral lineages may induce weaker antiviral interferon activity. The association between increased infectivity associated with spike mutations and possible innate immune evasion may be related to higher viral loads. P.1 viruses are associated with higher mortality rates, a phenotypic characteristic that may be related to their genetic background.