Enhanced reverse zoonotic potential and immune evasion by omicron JN.1 variant.

Publication date: Jul 18, 2025

SARS-CoV-2 infects not only humans but also animals, posing reverse zoonotic risks. As SARS-CoV-2 rapidly evolves, JN. 1 has become dominant globally. In this study, we determined the susceptibility of XBB. 1.16, EG. 5.1, BA. 2.86, and JN. 1 to 27 different animal angiotensin-converting enzyme 2 (ACE2) orthologs using pseudoviruses, and found that JN. 1 displayed substantially higher overall reverse zoonotic risk potential compared to other variants except for EG. 5.1. Live virus infection experiments further confirmed higher infectivity of JN. 1 than BA. 2.86. Mechanistic analyses revealed that L455S might be responsible for substantial increase in overall fusogenecity and infectivity by lowering S protein thermostability. Additionally, we also found that L455S mutation enhanced immune evasion of SARS-CoV-2, and XBB breakthrough infection increased levels of neutralization antibodies against JN. 1. Together, our findings offer a better mechanistic understanding of CoV entry, host range, evolution, and immunogenicity and highlight the importance of surveillance of susceptible hosts to prevent potential outbreaks.

Open Access PDF

Semantics

Original Article