Rational design of the zonulin inhibitor AT1001 derivatives as potential anti SARS-CoV-2.

ABSTRACT: Although vaccines are greatly mitigating the worldwide pandemic diffusion of SARS-Cov-2, therapeutics should provide many distinct advantages as complementary approach to control the viral spreading. Here, we report the development of new tripeptide derivatives of AT1001 against SARS-CoV-2 M^pro. By molecular modeling, a small compound library was rationally designed and filtered for enzymatic inhibition through FRET assay, leading to the identification of compound 4. X-ray crystallography studies provide insights into its binding mode and confirm the formation of a covalent bond with M^pro C145. In vitro antiviral tests indicate the improvement of biological activity of 4 respect to AT1001. In silico and X-ray crystallography analysis led to 58, showing a promising act

SUBMITTER: Di Micco S 

PROVIDER: S-EPMC9579148 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature