Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody

As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs). Here, we evaluate the potency of the previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cry-oelectron microscopy (cryo-EM) and X-ray crystallography. We show that mAb J08 has low nanomolar affinity against most VoCs and binds high on the receptor binding domain (RBD) ridge, away from many VoC mutations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy.

Automated summary

As the COVID-19 pandemic continues, highly potent monoclonal antibodies are needed to combat SARS-CoV-2 variants of concern. This study evaluates the efficacy of mAb J08 against these variants and investigates the binding details using cryo-EM and X-ray crystallography. The results demonstrate that mAb J08 has strong affinity against most variants and binds at a specific location on the receptor binding domain, away from the mutation sites. These findings further support the use of mAb J08 as a monoclonal therapy in ongoing clinical trials.