Pfizer announced promising clinical trials for their drug Paxlovid (Owen et al., 2021), an inhibitor of the main SARS-CoV-2 protease, Mpro (3CLpro, NSP5). In addition to being the main SARS-CoV-2 protease, Liu et al., (2021) discovered two different mechanisms whereby Mpro (NSP5) inactivates innate immunity. Both mechanisms involve Mpro (NSP5) and both mechanisms are blocked by small synthetic chemical compounds.

Liu et al., (2021) discovered that Mpro (NSP5) cleaves the ten amino-terminal residues from RIG-1, inactivating its ability to activate MAVS (VISA). They additionally showed that Mpro (NSP5) promotes the ubiquitination and subsequent proteosome-mediated degradation of MAVS. By this mechanism Mpro (NSP5) inactivates the innate immune system, blocking the ability of double-stranded viral RNA to activate the release of IFN. Identifying the role of Mpro (NSP5) in inhibiting innate immunity enabled Liu et al., to develop inhibitors of Mpro (NSP5) forming the basis for potential COVID-19 therapies.

Wenzel et al (2021) Discovered that the SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells

For a fuller discussion of the structure of Mpro and screening for inhibitory compounds see Jin et al (2020)

The comprehensive SARS-CoV-2 antibody catalog

ProSci offers SARS-CoV-2 Mpro (NSP5) antibodies as well as antibodies against other Non-Structural Proteins (NSPs) and Structural Proteins, N, M, E, and S, and recombinant proteins as reagents to further study viral infection and spread. ProSci’s comprehensive catalog of research reagents also includes tools for the study of innate immunity such as antibodies and recombinant proteins for RIG-1 and MAVS.