文献类型： 外文期刊

作者： Yuan, Shuofeng ¹ ; Yin, Xin ⁴ ; Meng, Xiangzhi ² ; Chan, Jasper Fuk-Woo ¹ ; Ye, Zi-Wei ² ; Riva, Laura ⁵ ; Pache, Lars ⁵ ;

作者机构： 1.Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Emerging Infect Dis, Pokfulam, Hong Kong, Peoples R China

2.Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, Pokfulam, Hong Kong, Peoples R China

3.Univ Hong Kong, Dept Clin Microbiol & Infect Control, Shenzhen Hosp, Shenzhen, Peoples R China

4.Harbin Vet Res Inst, Chinese Acad Agr Sci, State Key Lab Vet Biotechnol, Harbin, Peoples R China

5.Sanford Burnham Prebys Med Discovery Inst, Immun & Pathogenesis Program, Infect & Inflammatory Dis Ctr, La Jolla, CA USA

6.Hainan Med Univ, Hainan Med Univ Univ Hong Kong Joint Lab Trop Inf, Pokfulam, Hong Kong, Peoples R China

7.Univ Hong Kong, Hainan Med Univ Univ Hong Kong Joint Lab Trop Inf, Pokfulam, Hong Kong, Peoples R China

8.Univ Hong Kong, Sch Biomed Sci, Li Ka Shing Fac Med, Pokfulam, Hong Kong, Peoples R China

9.Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

10.Univ Hong Kong, Queen Mary Hosp, Dept Surg, Pokfulam, Hong Kong, Peoples R China

11.Univ Hong Kong, State Key Lab Synthet Chem, CAS HKU Joint Lab Metall Hlth & Environm, Dept Chem,Pokfulam, Hong Kong, Peoples R China

12.Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

13.Univ Copenhagen, Fac Hlth & Med Sci, Dept Mol & Cellular Med, Copenhagen Ctr Glyc, Copenhagen, Denmark

14.Univ Copenhagen, Fac Hlth & Med Sci, Dept Immunol & Microbiol, Copenhagen, Denmark

15.Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Div Pharmaceut Sci, La Jolla, CA 92093 USA

16.Univ Calif San Diego, Glycobiol Res & Training Ctr, La Jolla, CA 92093 USA

17.Univ Hong Kong, Li Ka Shing Fac Med, Dept Med, Pokfulam, Hong Kong, Peoples R China

18.Univ Hong Kong, Dr Li Dak Sum Res Ctr, Pokfulam, Hong Kong, Peoples R China

19.Scripps Res, Calibr, La Jolla, CA USA

期刊名称：NATURE （ 影响因子：42.778； 五年影响因子：46.486 ）

ISSN： 0028-0836

年卷期：

页码：

收录情况： SCI

摘要： The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 2003(1) and Middle East respiratory syndrome (MERS) in 2012(2). Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile(3)-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic ortherapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.