Work

Noncovalent SARS-CoV-2 main protease inhibitors targeting the catalytic dyad and primed substrate binding subsites

Year: 2026

Type: article

Abstract: antiviral assays. In addition, a room-temperature neutron structure of the MPro/KB-5 complex allowed direct determination of hydrogen positions, mapping intermolecular interactions and directly visualizing the protonation states and hydrogen bonding. Improved binding affinities of KK-7 and KB-3 through KB-6 could be attributed to the observed nonconventional S-H⋯F hydrogen bond and an additional conventional hydrogen bond between the carboxamide moieties and Q189. Our study provides binding details for the designed compounds and demonstrates the feasibility of our joint X-ray/neutron structure-assisted drug design approach to generate more potent noncovalent nonpeptidic MPro inhibitors.

Source: RSC Medicinal Chemistry

DOI: 10.1039/d6md00401f