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COVID-19 drug discovery and treatment options

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused substantial morbidity and mortality, and serious social and economic disruptions worldwide. Unvaccinated or incompletely vaccinated older individuals with underlying diseases are especially prone to severe disease. In patients with non-fatal disease, long COVID affecting multiple body systems may persist for months. Unlike SARS-CoV and Middle East respiratory syndrome coronavirus, which have either been mitigated or remained geographically restricted, SARS-CoV-2 has disseminated globally and is likely to continue circulating in humans with possible emergence of new variants that may render vaccines less effective. Thus, safe, effective and readily available COVID-19 therapeutics are urgently needed. In this Review, we summarize the major drug discovery approaches, preclinical antiviral evaluation models, representative virus-targeting and host-targeting therapeutic options, and key therapeutics currently in clinical use for COVID-19. Preparedness against future coronavirus pandemics relies not only on effective vaccines but also on broad-spectrum antivirals targeting conserved viral components or universal host targets, and new therapeutics that can precisely modulate the immune response during infection.

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Fig. 1: Drug discovery approaches for COVID-19 therapeutics.
Fig. 2: Key models for preclinical evaluation of COVID-19 therapeutic candidates.
Fig. 3: The replication cycle of SARS-CoV-2.
Fig. 4: Examples of virus-targeting and host-targeting COVID-19 therapeutic candidates.

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Acknowledgements

This study was partly supported by funding by the National Natural Science Foundation of China General Program (82272337); the Health and Medical Research Fund (20190572), Health Bureau, Government of the Hong Kong Special Administrative Region; the General Research Fund (17122322), Collaborative Research Fund (C7060-21G) and Theme-Based Research Scheme (T11-709/21-N), Research Grants Council, Government of the Hong Kong Special Administrative Region; Health@InnoHK, Innovation and Technology Commission, Government of the Hong Kong Special Administrative Region; the Partnership Programme of Enhancing Laboratory Surveillance and Investigation of Emerging Infectious Diseases and Antimicrobial Resistance for the Department of Health of the Hong Kong Special Administrative Region Government; the National Key Research and Development Program of China (projects 2021YFC0866100 and 2023YFC3041600); the Sanming Project of Medicine in Shenzhen, China (SZSM201911014); the High Level-Hospital Program, Health Commission of Guangdong Province, China; the Emergency Collaborative Project of Guangzhou Laboratory (EKPG22-01); the University of Hong Kong Outstanding Young Researcher Award; and the University of Hong Kong Research Output Prize (Li Ka Shing Faculty of Medicine); and by donations from the Shaw Foundation Hong Kong, Richard Yu and Carol Yu, Michael Seak-Kan Tong, May Tam Mak Mei Yin, Providence Foundation Limited (in memory of the late Lui Hac Minh), Lee Wan Keung Charity Foundation Limited, Hong Kong Sanatorium & Hospital, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, The Chen Wai Wai Vivien Foundation Limited, Chan Yin Chuen Memorial Charitable Foundation, Tse Kam Ming Laurence, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Pui-Sze Cheng, Perfect Shape Medical Limited, Kai Chong Tong, Tse Kam Ming Laurence, Foo Oi Foundation Limited and Betty Hing-Chu Lee, Ping Cham So, and Lo Ying Shek Chi Wai Foundation. The funding sources had no role in the study design, data collection, analysis, interpretation, or writing of the report.

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All authors researched data for the article, contributed substantially to discussion of the content, wrote the article, and reviewed and edited the manuscript before submission.

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Correspondence to Kwok-Yung Yuen.

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J.F.-W.C. has received travel grants from Pfizer Corporation Hong Kong and Astellas Pharma Hong Kong Corporation Ltd, and was an invited speaker for Gilead Sciences Hong Kong Ltd and Luminex Corporation. K.-Y.Y. is a shareholder of Hong Kong Universal Biologicals Company Ltd and Hong Kong Universal Vaccine Ltd, and collaborates with Sinovac Biotech Ltd and China National Pharmaceutical Group Co., Ltd (Sinopharm). J.F.-W.C., S.Y., H.C. and K.-Y.Y. have patent applications on a number of therapeutic candidates included in this article. S.S. declares no competing interests.

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Chan, J.FW., Yuan, S., Chu, H. et al. COVID-19 drug discovery and treatment options. Nat Rev Microbiol 22, 391–407 (2024). https://doi.org/10.1038/s41579-024-01036-y

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