Angew Chem Int Ed Engl . Molecular Insights into Small Molecule Drug Discovery for SARS-CoV-2

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Angew Chem Int Ed Engl


. 2020 Jul 29.
doi: 10.1002/anie.202008835. Online ahead of print.
Molecular Insights into Small Molecule Drug Discovery for SARS-CoV-2


Haibin Su ¹ , Hailei Su ² , Feng Zhou ³ , Ziru Huang ³ , Xiaohua Ma ⁴ , Kathiresan Natarajan ⁵ , Minchuan Zhang ⁴ , Yong Huang ³



Affiliations

• PMID: 32729180
• DOI: 10.1002/anie.202008835

Abstract

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 of protein-inhibitor interactions at 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 with the presence of promising inhibitors for COVID-19 in 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.

Keywords: Antivirial Drugs; COVID-19; Coronavirus; Modes of Action; SARS-COV-2.