CMX990 for COVID-19

 CMX990 has been reported as potentially beneficial for COVID-19 in the following studies.
COVID-19 involves the interplay of 350+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 10,000+ potential treatments. c19early.org analyzes 210+ treatments. We have not reviewed CMX990 in detail.
Elshan et al., Discovery of CMX990: A Potent SARS-CoV-2 3CL Protease Inhibitor Bearing a Novel Covalent Warhead, bioRxiv, doi:10.1101/2023.10.24.563688
ABSTRACTThere remains a need to develop novel SARS-CoV-2 therapeutic options that improve upon existing therapies by increased robustness of response, fewer safety liabilities, and global-ready accessibility. Functionally critical viral main protease (Mpro, 3CLpro) of SARS-CoV-2 is an attractive target due to its homology within the coronaviral family, and lack thereof towards human proteases. In this disclosure, we outline the advent of a novel SARS-CoV-2 3CLproinhibitor, CMX990, bearing an unprecedented trifluoromethoxymethyl ketone warhead. Compared with the marketed drug nirmatrelvir (combination with ritonavir = PaxlovidTM), CMX990 has distinctly differentiated potency (∼5x more potent in primary cells) and humanin vitroclearance (>4x better microsomal clearance and >10x better hepatocyte clearance), with goodin vitro-in vivocorrelation. Based on its compelling preclinical profile and projected once or twice a day dosing supporting unboosted oral therapy in humans, CMX990 advanced to a Phase 1 clinical trial as an oral drug candidate for SARS-CoV-2.
Dayan Elshan et al., Discovery of CMX990: A Potent SARS-CoV-2 3CL Protease Inhibitor Bearing a Novel Warhead, Journal of Medicinal Chemistry, doi:10.1021/acs.jmedchem.3c01938
Bolinger et al., Lessons learnt from broad-spectrum coronavirus antiviral drug discovery, Expert Opinion on Drug Discovery, doi:10.1080/17460441.2024.2385598
Yang et al., Progress in Research on Inhibitors Targeting SARS-CoV-2 Main Protease (Mpro), ACS Omega, doi:10.1021/acsomega.4c03023