Molecular modeling-guided optimization of acetylcholinesterase reactivators: A proof for reactivation of covalently inhibited targets.

ABSTRACT: Covalent drugs have been intensively studied in some very important fields such as anti-tumor and anti-virus, including the currently global-spread SARS-CoV-2. However, these drugs may interact with a variety of biological macromolecules and cause serious toxicology, so how to reactivate the inhibited targets seems to be imperative in the near future. Organophosphate was an extreme example, which could form a covalent bound easily with acetylcholinesterase and irreversibly inhibited the enzyme, causing high toxicology. Some nucleophilic oxime reactivators for organophosphate poisoned acetylcholinesterase had been developed, but the reactivation process was still less understanding. Herein, we proposed there should be a pre-reactivated pose during the reactivating process and compounds whos

SUBMITTER: Wei Z 

PROVIDER: S-EPMC7877871 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature