Evolution of BA.2.86 to JN.1 reveals that functional changes in non-structural viral proteins are required for fitness of SARS-CoV-2.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is still circulating among humans, leading to the continuous evolution. SARS-CoV-2 Omicron JN.1 evolved from a distinct SARS-CoV-2 lineage, BA.2.86, and spread rapidly worldwide. It is unclear why BA.2.86 did not become dominant and was quickly replaced by JN.1, which possesses one amino acid substitution in the spike protein (S:L455S) and two in the non-spike proteins NSP6 and ORF7b (NSP6:R252K and ORF7b:F19L) compared to BA.2.86. Here, we utilized recombinant viruses to elucidate the impact of these mutations on the virological characteristics of JN.1. We found that the mutation in the spike attenuated viral replication, while the non-spike mutations acted synergistic

SUBMITTER: Tsujino S 

PROVIDER: S-EPMC12548449 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature