A New Fragment-Based Pharmacophore Virtual Screening Workflow Identifies Potent Inhibitors of SARS-CoV-2 NSP13 Helicase.

Herein we report the in silico discovery of 13 novel micromolar potent inhibitors of the SARS-CoV-2 NSP13 helicase validated in cellular antiviral and biophysical ThermoFluor assays. The compounds, discovered using a novel fragment-based pharmacophore virtual screening workflow named FragmentScout, enable the advancement of novel antiviral agents. FragmentScout uses publicly accessible structural data of the SARS-CoV-2 NSP13 helicase, which was previously generated at the Diamond LightSource by XChem high-throughput crystallographic fragment screening.

A small-molecule SARS-CoV-2 inhibitor targeting the membrane protein.

The membrane (M) protein of betacoronaviruses is well conserved and has a key role in viral assembly. Here we describe the identification of JNJ-9676, a small-molecule inhibitor targeting the coronavirus M protein. JNJ-9676 demonstrates in vitro nanomolar antiviral activity against SARS-CoV-2, SARS-CoV and sarbecovirus strains from bat and pangolin zoonotic origin.