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Molecular Insights into Small‐Molecule Drug Discovery for SARS‐CoV‐2
Author(s) -
Su Hailei,
Zhou Feng,
Huang Ziru,
Ma Xiaohua,
Natarajan Kathiresan,
Zhang Minchuan,
Huang Yong,
Su Haibin
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202008835
Subject(s) - drug discovery , computational biology , proteases , context (archaeology) , biology , covid-19 , antiviral drug , virology , virus , bioinformatics , enzyme , medicine , disease , biochemistry , infectious disease (medical specialty) , paleontology , pathology
The mainstream approach to antiviral drugs against COVID‐19 is to focus on key stages of the SARS‐CoV‐2 life cycle. The vast majority of candidates under investigation are repurposed from agents of other indications. Understanding protein–inhibitor interactions at the molecular scale will provide crucial insights for drug discovery to stop this pandemic. In this article, we summarize and analyze the most recent structural data on several viral targets in the presence of promising inhibitors for COVID‐19 in the context of the perspective of modes of action (MOA) to unravel insightful mechanistic features with atomistic resolution. The targets include spike glycoprotein and various host proteases mediating the entry of the virus into the cells, viral chymotrypsin‐ and papain‐like proteases, and RNA‐dependent RNA polymerase. The main purpose of this review is to present detailed MOA analysis to inspire fresh ideas for both de novo drug design and optimization of known scaffolds to combat COVID‐19.