Development of therapeutics for SARS-CoV-2 infection

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

We have examined a variety of compounds that have reportedly been active against SARS-CoV. We specifically selected and synthesized a panel of active compounds based on previously known structures and their activity against SARS-CoV. We have now identified two small molecule compounds, GRL-1720 and GRL-2420, both of which target the main protease (Mpro) of SARS-CoV-2 and potently block the infectivity, replication, and cytopathicity of SARS-CoV-2WK-521. We found highly neutralizing COVID-19 convalescent plasmas potently block SARS-CoV-2 replication and pneumonia in Syrian hamsters. In addition, SARS-CoV-2-neutralizing humoral IgA response occurs earlier but modest and diminishes faster compared to IgG response. We developed a novel highly quantitative and reproducible assay for the detection of anti-SARS-CoV-2 IgG and IgM antibodies. Other studies found correlates of neutralizing/SARS-CoV-2-S1-binding antibody response with adverse effects and immune kinetics in BNT162b2-vaccinated individuals. We reported the synthesis, structure-activity relationship studies, enzyme inhibition, antiviral activity, and X-ray crystallographic studies of 5-chloropyridinyl indole carboxylate derivatives as a potent class of SARS-CoV-2 chymotrypsin-like protease inhibitors.