Chang, Chung-KeLin, Shan-MengRoshan, SatangeLin, Shih-ChaoSun, Sin-CihHung-Yi, WuKehn-Hall, KyleneHou, Ming-Hon2021-07-092021-07-092021-04-15http://hdl.handle.net/10919/104125To 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.application/pdfenAttribution-NonCommercial-NoDerivatives 4.0 InternationalCOVID-19PPIIsAntiviral strategyDrug discoverySARS-CoV-2Article - Refereedhttps://doi.org/10.1016/j.csbj.2021.04.00319