Discovery of Galloyl-Flavonoid Conjugates as SARS-CoV-2 3CL^pro Inhibitors: Understanding Binding Interactions Through Computational Approaches.

ABSTRACT: The emergence of SARS-CoV-2 in 2019 posed significant global public health challenges. One of the most promising targets for novel antiviral drug development is the SARS-CoV-2 main protease (3CL^pro). In this study, fragment molecular orbital (FMO) calculations were conducted to provide guidance for the structural modification of natural flavonoids, identifying the pyrogallol moiety as a key candidate. Natural flavonoids were chemically modified to generate 33 semi-synthetic derivatives through the introduction of various functional groups. Our findings revealed that the incorporation of a galloyl moiety significantly enhances anti-proteolytic activity against SARS-CoV-2 3CL^pro, achieving up to a 23-fold increase compared to the activity of the parent compounds. Notabl

SUBMITTER: Khamto N 

PROVIDER: S-EPMC12524796 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature