COVID-19 therapeutics: Small-molecule drug development targeting SARS-CoV-2 main protease

Thales Kronenberger; Stefan A Laufer; Thanigaimalai Pillaiyar

doi:10.1016/j.drudis.2023.103579

COVID-19 therapeutics: Small-molecule drug development targeting SARS-CoV-2 main protease

Drug Discov Today. 2023 Jun;28(6):103579. doi: 10.1016/j.drudis.2023.103579. Epub 2023 Apr 5.

Authors

Thales Kronenberger¹, Stefan A Laufer², Thanigaimalai Pillaiyar³

Affiliations

¹ Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry and Tuebingen Center for Academic Drug Discovery, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, 72076 Tübingen, Germany.
² Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry and Tuebingen Center for Academic Drug Discovery, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, 72076 Tübingen, Germany.
³ Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry and Tuebingen Center for Academic Drug Discovery, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany. Electronic address: thanigaimalai.pillaiyar@uni-tuebingen.de.

Abstract

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the causative factor behind the 2019 global coronavirus pandemic (COVID-19). The main protease, known as M^pro, is encoded by the viral genome and is essential for viral replication. It has also been an effective target for drug development. In this review, we discuss the rationale for inhibitors that specifically target SARS-CoV-2 M^pro. Small molecules and peptidomimetic inhibitors are two types of inhibitor with various modes of action and we focus here on novel inhibitors that were only discovered during the COVID-19 pandemic highlighting their binding modes and structures.

Keywords: Antiviral; COVID-19; Coronavirus; Protease inhibitors; SARS-CoV-2.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / chemistry
Antiviral Agents / pharmacology
Antiviral Agents / therapeutic use
COVID-19*
Drug Development
Humans
Molecular Docking Simulation
Pandemics
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology
Protease Inhibitors / therapeutic use
SARS-CoV-2 / metabolism

Substances

3C-like proteinase, SARS-CoV-2
Antiviral Agents
Protease Inhibitors