He, P.; Song, Y.; Guo, C.; Yu, L.; Yu, Y.; Jian, F.; Shao, F.; Cao, Y.

The recent global expansion of the SARS-CoV-2 variant NB.1.8.1 has driven the emergence of sublineages PQ.16.1.1 and RK.1, which independently acquired the D420N mutation in their receptor-binding domains and and now dominate the Asia-Pacific region. Evaluations utilizing surface plasmon resonance and pseudovirus assays demonstrate that these sublineages exhibit significantly reduced human ACE2 receptor engagement compared to their parental strain. However, this functional cost is offset by a marked ability to evade humoral immunity, specifically demonstrating profound resistance to Class 1 neutralizing monoclonal antibodies and convalescent plasma from Wuhan-Hu-1-primed individuals. This convergent evolution exemplifies a classical viral trade-off, sacrificing receptor binding efficiency to escape population-level immune pressure. Consequently, these findings suggest these variants will soon spread globally and emphasize the critical need for ongoing surveillance to monitor D420N-carrying lineages.