TY - JOUR

T1 - Clofazimine broadly inhibits coronaviruses including SARS-CoV-2

AU - Yuan, Shuofeng

AU - Yin, Xin

AU - Meng, Xiangzhi

AU - Chan, Jasper Fuk Woo

AU - Ye, Zi Wei

AU - Riva, Laura

AU - Pache, Lars

AU - Chan, Chris Chun Yiu

AU - Lai, Pok Man

AU - Chan, Chris Chung Sing

AU - Poon, Vincent Kwok Man

AU - Lee, Andrew Chak Yiu

AU - Matsunaga, Naoko

AU - Pu, Yuan

AU - Yuen, Chun Kit

AU - Cao, Jianli

AU - Liang, Ronghui

AU - Tang, Kaiming

AU - Sheng, Li

AU - Du, Yushen

AU - Xu, Wan

AU - Lau, Chit Ying

AU - Sit, Ko Yung

AU - Au, Wing Kuk

AU - Wang, Runming

AU - Zhang, Yu Yuan

AU - Tang, Yan Dong

AU - Clausen, Thomas Mandel

AU - Pihl, Jessica

AU - Oh, Juntaek

AU - Sze, Kong Hung

AU - Zhang, Anna Jinxia

AU - Chu, Hin

AU - Kok, Kin Hang

AU - Wang, Dong

AU - Cai, Xue Hui

AU - Esko, Jeffrey D.

AU - Hung, Ivan Fan Ngai

AU - Li, Ronald Adolphus

AU - Chen, Honglin

AU - Sun, Hongzhe

AU - Jin, Dong Yan

AU - Sun, Ren

AU - Chanda, Sumit K.

AU - Yuen, Kwok Yung

PY - 2021

Y1 - 2021

N2 - COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of the century after severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) since 20122. Treatment options for CoVs are largely lacking. Here we show that clofazimine, an anti-leprosy drug with a favourable safety profile3, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 and MERS-CoV replication in multiple in vitro systems. The FDA-approved molecule was found to inhibit viral spike-mediated cell fusion and viral helicase activity. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and faecal viral shedding, and also mitigated inflammation associated with viral infection. Combinatorial application of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted upper respiratory tract viral shedding. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. Taken together, our data provide evidence that clofazimine may have a role in the control of the current pandemic SARS-CoV-2, and, possibly most importantly, emerging CoVs of the future.

AB - COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of the century after severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) since 20122. Treatment options for CoVs are largely lacking. Here we show that clofazimine, an anti-leprosy drug with a favourable safety profile3, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 and MERS-CoV replication in multiple in vitro systems. The FDA-approved molecule was found to inhibit viral spike-mediated cell fusion and viral helicase activity. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and faecal viral shedding, and also mitigated inflammation associated with viral infection. Combinatorial application of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted upper respiratory tract viral shedding. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. Taken together, our data provide evidence that clofazimine may have a role in the control of the current pandemic SARS-CoV-2, and, possibly most importantly, emerging CoVs of the future.

U2 - 10.1038/s41586-021-03431-4

DO - 10.1038/s41586-021-03431-4

M3 - Journal article

C2 - 33727703

AN - SCOPUS:85102599258

VL - 593

SP - 418

EP - 423

JO - Nature

JF - Nature

SN - 0028-0836

ER -