Structure-based design of 5'-substituted 1,2,3-triazolylated oseltamivir derivatives as potent influenza neuraminidase inhibitors.

ABSTRACT: Resistant viruses containing mutant neuraminidases (NAs) with diminished drug affinity continue to emerge, and new anti-influenza agents are urgently required. Several potent inhibitors targeting the hydrophobic 150-cavity of viral NAs have been developed by modifying the antiviral drugs, oseltamivir carboxylate (OSC) and zanamivir, with hydrophobic groups. Here, we describe a different strategy for exploring novel and efficient NA inhibitors by targeting the charged amino acid residues around the entrance to the 150-cavity. We synthesized a C5-substituted OSC derivative (1e) with a 4'-phenyl-1,2,3-triazolyl group capable of entering the 150-cavity, and solved the crystal structure of 1e in complex with influenza A virus N5 NA. Using the resulting structural information, we next designed a

SUBMITTER: Wang P 

PROVIDER: S-EPMC8696196 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature