Targeting furin, a cellular proprotein convertase, for COVID-19 prevention and therapeutics

Xia Jiang; Dabing Li; Mazaher Maghsoudloo; Xinghai Zhang; Wenzhe Ma; Junjiang Fu

doi:10.1016/j.drudis.2024.104026

Targeting furin, a cellular proprotein convertase, for COVID-19 prevention and therapeutics

Drug Discov Today. 2024 May 17:104026. doi: 10.1016/j.drudis.2024.104026. Online ahead of print.

Authors

Xia Jiang¹, Dabing Li², Mazaher Maghsoudloo³, Xinghai Zhang⁴, Wenzhe Ma⁵, Junjiang Fu⁶

Affiliations

¹ Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China; Department of Reproductive Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China; The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau.
² Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China; School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, China.
³ Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China.
⁴ CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.
⁵ The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau. Electronic address: wzma@must.edu.mo.
⁶ Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China; Department of Reproductive Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China. Electronic address: fujunjiang@swmu.edu.cn.

PMID: 38762086
DOI: 10.1016/j.drudis.2024.104026

Abstract

SARS-CoV-2 has triggered an international outbreak of the highly contagious acute respiratory disease known as COVID-19. Identifying key targets in the virus infection lifecycle is crucial for developing effective prevention and therapeutic strategies against it. Furin is a serine endoprotease that belongs to the family of proprotein convertases and plays a critical role in the entry of host cells by SARS-CoV-2. Furin can cleave a specific S1/S2 site, PRRAR, on the spike protein of SARS-CoV-2, which promotes viral transmission by facilitating membrane fusion. Hence, targeting furin could hold clinical implications for the prevention and treatment of COVID-19. This review offers an overview of furin's structure, substrates, function, and inhibitors, with a focus on its potential role in SARS-CoV-2 infection.

Keywords: COVID-19; SARS-CoV-2; furin; furin inhibitors; therapeutics.

Publication types

Review