Clofazimine broadly inhibits coronaviruses including SARS-CoV-2
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Clofazimine broadly inhibits coronaviruses including SARS-CoV-2. / Yuan, Shuofeng; Yin, Xin; Meng, Xiangzhi; Chan, Jasper Fuk Woo; Ye, Zi Wei; Riva, Laura; Pache, Lars; Chan, Chris Chun Yiu; Lai, Pok Man; Chan, Chris Chung Sing; Poon, Vincent Kwok Man; Lee, Andrew Chak Yiu; Matsunaga, Naoko; Pu, Yuan; Yuen, Chun Kit; Cao, Jianli; Liang, Ronghui; Tang, Kaiming; Sheng, Li; Du, Yushen; Xu, Wan; Lau, Chit Ying; Sit, Ko Yung; Au, Wing Kuk; Wang, Runming; Zhang, Yu Yuan; Tang, Yan Dong; Clausen, Thomas Mandel; Pihl, Jessica; Oh, Juntaek; Sze, Kong Hung; Zhang, Anna Jinxia; Chu, Hin; Kok, Kin Hang; Wang, Dong; Cai, Xue Hui; Esko, Jeffrey D.; Hung, Ivan Fan Ngai; Li, Ronald Adolphus; Chen, Honglin; Sun, Hongzhe; Jin, Dong Yan; Sun, Ren; Chanda, Sumit K.; Yuen, Kwok Yung.
I: Nature, Bind 593, 2021, s. 418–423.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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 -
ID: 258895385