Structural basis for the synergistic neutralization of coxsackievirus B1 by a triple-antibody cocktail

Two antibodies show broad, synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD

“…Typically, antibody cocktail rational design tends to select non-competing nAbs ( Crowe 2022 , Carter and Rajpal 2022 ). However, our recent work on coxsackievirus described the benefit of a counterintuitive antibody cocktail containing three competing nAbs that target the vulnerable receptor-binding determinant ( Zheng et al 2022 ). We observed synergy among the competing nAbs through a cooperative mechanism in which the binding of one nAb added or potentiated the binding of another nAb with an overlapping epitope, and these multi-antibody functions cooperatively disrupted the coxsackievirus virions ( Zheng et al 2022 ).…”

“…However, our recent work on coxsackievirus described the benefit of a counterintuitive antibody cocktail containing three competing nAbs that target the vulnerable receptor-binding determinant ( Zheng et al 2022 ). We observed synergy among the competing nAbs through a cooperative mechanism in which the binding of one nAb added or potentiated the binding of another nAb with an overlapping epitope, and these multi-antibody functions cooperatively disrupted the coxsackievirus virions ( Zheng et al 2022 ). SARS-CoV-2 antibody cocktails that are approved or in development always are selected based on non-overlapping antibody designs.…”

A counterintuitive antibody cocktail disrupts coxsackievirus

“…But what is the best way to go from isolating individual monoclonal antibodies to figuring out which combinations function best together? In this issue, Zheng and colleagues present an in-depth mechanistic investigation of a combination of three neutralizing mAbs that all compete with the coxsackievirus-adenovirus receptor (CAR) for binding to coxsackievirus B1 (CVB1) ( Zheng et al., 2022 ). The authors selected murine mAbs that disrupted the binding of recombinant CAR to CVB1 virions in an ELISA.…”