tetano
Editor, Senior Moderator
Nature
. 2021 Mar 16.
doi: 10.1038/s41586-021-03431-4. Online ahead of print.
Clofazimine broadly inhibits coronaviruses including SARS-CoV-2
Shuofeng Yuan[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Xin Yin[SUP] #[/SUP][SUP] 4 5 [/SUP], Xiangzhi Meng[SUP] #[/SUP][SUP] 2 [/SUP], Jasper Fuk-Woo Chan[SUP] #[/SUP][SUP] 3 6 [/SUP], Zi-Wei Ye[SUP] #[/SUP][SUP] 2 [/SUP], Laura Riva[SUP] 5 7 [/SUP], Lars Pache[SUP] 5 [/SUP], Chris Chun-Yiu Chan[SUP] 2 [/SUP], Pok-Man Lai[SUP] 2 [/SUP], Chris Chung-Sing Chan[SUP] 2 [/SUP], Vincent Kwok-Man Poon[SUP] 2 [/SUP], Andrew Chak-Yiu Lee[SUP] 2 [/SUP], Naoko Matsunaga[SUP] 5 [/SUP], Yuan Pu[SUP] 5 [/SUP], Chun-Kit Yuen[SUP] 2 [/SUP], Jianli Cao[SUP] 2 [/SUP], Ronghui Liang[SUP] 2 [/SUP], Kaiming Tang[SUP] 2 [/SUP], Li Sheng[SUP] 8 9 [/SUP], Yushen Du[SUP] 9 [/SUP], Wan Xu[SUP] 8 [/SUP], Chit-Ying Lau[SUP] 8 [/SUP], Ko-Yung Sit[SUP] 10 [/SUP], Wing-Kuk Au[SUP] 10 [/SUP], Runming Wang[SUP] 11 [/SUP], Yu-Yuan Zhang[SUP] 4 [/SUP], Yan-Dong Tang[SUP] 4 [/SUP], Thomas Mandel Clausen[SUP] 12 13 [/SUP], Jessica Pihl[SUP] 12 14 [/SUP], Juntaek Oh[SUP] 12 15 [/SUP], Kong-Hung Sze[SUP] 1 2 [/SUP], Anna Jinxia Zhang[SUP] 1 2 [/SUP], Hin Chu[SUP] 1 2 [/SUP], Kin-Hang Kok[SUP] 1 2 [/SUP], Dong Wang[SUP] 12 15 [/SUP], Xue-Hui Cai[SUP] 4 [/SUP], Jeffrey D Esko[SUP] 12 16 [/SUP], Ivan Fan-Ngai Hung[SUP] 17 [/SUP], Ronald Adolphus Li[SUP] 18 [/SUP], Honglin Chen[SUP] 1 2 [/SUP], Hongzhe Sun[SUP] 11 [/SUP], Dong-Yan Jin[SUP] 8 [/SUP], Ren Sun[SUP] 19 20 [/SUP], Sumit K Chanda[SUP] 21 [/SUP], Kwok-Yung Yuen[SUP] 22 23 24 25 [/SUP]
Affiliations
Abstract
COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of the century after severe acute respiratory syndrome (SARS) in 2003[SUP]1[/SUP] and Middle East respiratory syndrome (MERS) since 2012[SUP]2[/SUP]. Treatment options for CoVs are largely lacking. Here we show that clofazimine, an anti-leprosy drug with a favourable safety profile[SUP]3[/SUP], 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.
. 2021 Mar 16.
doi: 10.1038/s41586-021-03431-4. Online ahead of print.
Clofazimine broadly inhibits coronaviruses including SARS-CoV-2
Shuofeng Yuan[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Xin Yin[SUP] #[/SUP][SUP] 4 5 [/SUP], Xiangzhi Meng[SUP] #[/SUP][SUP] 2 [/SUP], Jasper Fuk-Woo Chan[SUP] #[/SUP][SUP] 3 6 [/SUP], Zi-Wei Ye[SUP] #[/SUP][SUP] 2 [/SUP], Laura Riva[SUP] 5 7 [/SUP], Lars Pache[SUP] 5 [/SUP], Chris Chun-Yiu Chan[SUP] 2 [/SUP], Pok-Man Lai[SUP] 2 [/SUP], Chris Chung-Sing Chan[SUP] 2 [/SUP], Vincent Kwok-Man Poon[SUP] 2 [/SUP], Andrew Chak-Yiu Lee[SUP] 2 [/SUP], Naoko Matsunaga[SUP] 5 [/SUP], Yuan Pu[SUP] 5 [/SUP], Chun-Kit Yuen[SUP] 2 [/SUP], Jianli Cao[SUP] 2 [/SUP], Ronghui Liang[SUP] 2 [/SUP], Kaiming Tang[SUP] 2 [/SUP], Li Sheng[SUP] 8 9 [/SUP], Yushen Du[SUP] 9 [/SUP], Wan Xu[SUP] 8 [/SUP], Chit-Ying Lau[SUP] 8 [/SUP], Ko-Yung Sit[SUP] 10 [/SUP], Wing-Kuk Au[SUP] 10 [/SUP], Runming Wang[SUP] 11 [/SUP], Yu-Yuan Zhang[SUP] 4 [/SUP], Yan-Dong Tang[SUP] 4 [/SUP], Thomas Mandel Clausen[SUP] 12 13 [/SUP], Jessica Pihl[SUP] 12 14 [/SUP], Juntaek Oh[SUP] 12 15 [/SUP], Kong-Hung Sze[SUP] 1 2 [/SUP], Anna Jinxia Zhang[SUP] 1 2 [/SUP], Hin Chu[SUP] 1 2 [/SUP], Kin-Hang Kok[SUP] 1 2 [/SUP], Dong Wang[SUP] 12 15 [/SUP], Xue-Hui Cai[SUP] 4 [/SUP], Jeffrey D Esko[SUP] 12 16 [/SUP], Ivan Fan-Ngai Hung[SUP] 17 [/SUP], Ronald Adolphus Li[SUP] 18 [/SUP], Honglin Chen[SUP] 1 2 [/SUP], Hongzhe Sun[SUP] 11 [/SUP], Dong-Yan Jin[SUP] 8 [/SUP], Ren Sun[SUP] 19 20 [/SUP], Sumit K Chanda[SUP] 21 [/SUP], Kwok-Yung Yuen[SUP] 22 23 24 25 [/SUP]
Affiliations
- PMID: 33727703
- DOI: 10.1038/s41586-021-03431-4
Abstract
COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of the century after severe acute respiratory syndrome (SARS) in 2003[SUP]1[/SUP] and Middle East respiratory syndrome (MERS) since 2012[SUP]2[/SUP]. Treatment options for CoVs are largely lacking. Here we show that clofazimine, an anti-leprosy drug with a favourable safety profile[SUP]3[/SUP], 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.