Unraveling the Structural Basis for Antibody Synergy against Escape-Resistant Nipah Virus Mutant

Effective countermeasures are urgently needed to mitigate the potential pandemic threat posed by the highly pathogenic Nipah virus, which is capable of person-to-person transmission. This study evaluates the efficacy of three antibodies (m102.4, 1E5, and n425) against the V507I mutant strains and explores the synergistic mechanism between n425 and m102.4 using molecular dynamics simulations. Our results indicate that the V507I mutation mediates immune escape from m102.4, whereas 1E5 remains effective against the mutant, attributable to stable hydrogen bonds within a critical loop region. Furthermore, the energy calculations reveal pronounced synergy in the n425-m102.4 combination. Specifically, the binding of n425 stabilizes key residues within m102.4's loop region, thereby promoting a more stable conformation of the n425-m102.4-WT complex for effective binding with the G protein. We hope that this work will provide theoretical insights for the development and optimization of targeted NiV therapies.