Chloroacetamide Mpro inhibitor 25 for COVID-19

Chloroacetamide Mpro inhibitor 25 may be beneficial for COVID-19 according to the study below. COVID-19 involves the interplay of 500+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 12,000+ potential treatments. c19early.org analyzes 220+ treatments. We have not reviewed chloroacetamide Mpro inhibitor 25 in detail.
Bao et al., Structure-Based Design of New Nonpeptidic Covalent Mpro Inhibitors against SARS-CoV-2 and Omicron Variants, ACS Bio & Med Chem Au, doi:10.1021/acsbiomedchemau.6c00072
Abstract The main protease (Mpro) is a prime target for anti-SARS-CoV-2 drugs. Herein, we describe the structure-based covalent modifications that generate new nonpeptidic covalent Mpro inhibitors. The compounds exhibit strong inhibition against Mpro at submicromolar levels. The deuterated lead compound exhibits submicromolar antiviral activity against wild-type SARS-CoV-2 and Omicron variants. Biolayer interferometry analysis indicates a strong binding affinity for Mpro. The mass spectrometry results confirm the covalent bonding of the compound with the cysteine residue of Mpro. Taken together, the data may support the deuterated compound as a new lead for developing anti-SARS-CoV-2 drugs and further reveal the feasibility of using chloroacetyl for structure-based covalent drug design.