Development of a novel monoclonal antibody that targets SARS-CoV-2 3a

The damage to the lung and other organs during SARS-CoV-2 infection is driven by inflammation induced by the virus. Independent of vaccine-based strategies, distinct efforts to curtail severe acute and chronic lung disease by targeting inflammation following infection have not yet been proven completely safe and efficacious. The complex interactions between SARS-CoV-2 virus and the immune system during virus replication appear to be distinct from that of other respiratory viruses and are not yet entirely understood. There are SARS-CoV/SARS-CoV-2 gene products demonstrated to induce and modulate inflammation. This includes viroporin 3a, the virus-encoded K+ efflux membrane protein on the cell surface that activates the NLRP3 inflammasome. The exposed N-terminal 42 amino acid 3a ectodomain extends out from the channel pore and appears to be under strong immune selection based on our pan-genome covariance analysis of lineage B b-coronaviruses. We propose screening and identifying human mAbs with high affinity to exposed extracellular regions of 3a including ectodomain. Using cloned and purified mAbs as candidates, we will use established screens to find those that inhibit 3a activities including viroporin ion channel activity, and may then reduce both inflammation and pathogenesis.