Targeting protein-protein interaction interfaces in COVID-19 drug discovery

Chung-Ke Chang; Shan-Meng Lin; Roshan Satange; Shih-Chao Lin; Sin-Cih Sun; Hung-Yi Wu; Kylene Kehn-Hall; Ming-Hon Hou

doi:10.1016/j.csbj.2021.04.003

Targeting protein-protein interaction interfaces in COVID-19 drug discovery

Comput Struct Biotechnol J. 2021:19:2246-2255. doi: 10.1016/j.csbj.2021.04.003. Epub 2021 Apr 15.

Authors

Chung-Ke Chang¹, Shan-Meng Lin², Roshan Satange^{2

3}, Shih-Chao Lin⁴, Sin-Cih Sun², Hung-Yi Wu⁵, Kylene Kehn-Hall⁶, Ming-Hon Hou^{2

3}

Affiliations

¹ Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
² Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung 402, Taiwan.
³ Ph.D. Program in Medical Biotechnology, National Chung Hsing University, Taichung 402, Taiwan.
⁴ Bachelor Degree Program in Marine Biotechnology, National Taiwan Ocean University, Keelung 20224, Taiwan.
⁵ Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing University, Taichung 40227, Taiwan.
⁶ Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Virginia 24061, United States.

Abstract

To date, the COVID-19 pandemic has claimed over 1 million human lives, infected another 50 million individuals and wreaked havoc on the global economy. The crisis has spurred the ongoing development of drugs targeting its etiological agent, the SARS-CoV-2. Targeting relevant protein-protein interaction interfaces (PPIIs) is a viable paradigm for the design of antiviral drugs and enriches the targetable chemical space by providing alternative targets for drug discovery. In this review, we will provide a comprehensive overview of the theory, methods and applications of PPII-targeted drug development towards COVID-19 based on recent literature. We will also highlight novel developments, such as the successful use of non-native protein-protein interactions as targets for antiviral drug screening. We hope that this review may serve as an entry point for those interested in applying PPIIs towards COVID-19 drug discovery and speed up drug development against the pandemic.

Keywords: Antiviral strategy; COVID-19; Drug discovery; PPIIs; SARS-CoV-2.

Publication types

Review