Drug repurposing for the treatment of COVID-19

Yuri Kato, Kazuhiro Nishiyama, Akiyuki Nishimura, Takamasa Noda, Kaori Okabe, Takahiro Kusakabe, Yasunari Kanda, Motohiro Nishida, Yuri Kato, Kazuhiro Nishiyama, Akiyuki Nishimura, Takamasa Noda, Kaori Okabe, Takahiro Kusakabe, Yasunari Kanda, Motohiro Nishida

Abstract

Coronavirus disease 2019 (COVID-19) remains prevalent worldwide since its onset was confirmed in Wuhan, China in 2019. Vaccines against the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have shown a preventive effect against the onset and severity of COVID-19, and social and economic activities are gradually recovering. However, the presence of vaccine-resistant variants has been reported, and the development of therapeutic agents for patients with severe COVID-19 and related sequelae remains urgent. Drug repurposing, also called drug repositioning or eco-pharma, is the strategy of using previously approved and safe drugs for a therapeutic indication that is different from their original indication. The risk of severe COVID-19 and mortality increases with advancing age, cardiovascular disease, hypertension, diabetes, and cancer. We have reported three protein-protein interactions that are related to heart failure, and recently identified that one mechanism increases the risk of SARS-CoV-2 infection in mammalian cells. This review outlines the global efforts and outcomes of drug repurposing research for the treatment of severe COVID-19. It also discusses our recent finding of a new protein-protein interaction that is common to COVID-19 aggravation and heart failure.

Keywords: Cardiomyocyte; Eco-pharma; NADPH oxidase; Protein–protein interaction; Transient receptor potential channel.

Conflict of interest statement

Declaration of competing interest The authors declare no conflicts of interest.

Copyright © 2022 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
Possible drug discovery targets for developing COVID-19 treatments. PLpro: papain-like protease, CLPro: 3-chymotrypsin-like protease (main protease), ACE2: angiotensin-converting enzyme 2, TMPRSS2: transmembrane protease, serine 2.
Fig. 2
Fig. 2
Protein–protein interactions in pathological cardiovascular tissue that could be targets of drug repurposing efforts. TRPC3: transient receptor potential canonical subfamily member 3, Nox2: NADPH oxidase, P2Y6R: purinergic P2Y6 receptor, AT1R: angiotensin II type 1 receptor, Drp1: dynamin-related protein 1.
Fig. 3
Fig. 3
Risk factor-induced TRPC3–Nox2 complex formation mediates COVID-19 aggravation. ARDS: acute respiratory distress syndrome.

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