Structure-guided design, synthesis and evaluation of oxazolidinone-based inhibitors of norovirus 3CL protease.
Basic Information
ID: ALA4138240
Journal: Eur J Med Chem
Title: Structure-guided design, synthesis and evaluation of oxazolidinone-based inhibitors of norovirus 3CL protease.
Authors: Damalanka VC, Kim Y, Galasiti Kankanamalage AC, Rathnayake AD, Mehzabeen N, Battaile KP, Lovell S, Nguyen HN, Lushington GH, Chang KO, Groutas WC.
Abstract: Acute nonbacterial gastroenteritis caused by noroviruses constitutes a global public health concern and a significant economic burden. There are currently no small molecule therapeutics or vaccines for the treatment of norovirus infections. A structure-guided approach was utilized in the design of a series of inhibitors of norovirus 3CL protease that embody an oxazolidinone ring as a novel design element for attaining optimal binding interactions. Low micromolar cell-permeable inhibitors that display anti-norovirus activity have been identified. The mechanism of action, mode of binding, and structural rearrangements associated with the interaction of the inhibitors and the enzyme were elucidated using X-ray crystallography.
CiteXplore: 29227928
DOI: 10.1016/j.ejmech.2017.12.014
Patent ID: ┄