A Small-Scale Medication of Leflunomide as a Treatment of COVID-19 in an Open-Label Blank-Controlled Clinical Trial  

作　　者：Ke Hu Mengmei Wang Yang Zhao Yunting Zhang Tao Wang Zhishui Zheng Xiaochen Li Shaolin Zeng Dong Zhao Honglin Li Ke Xu Ke Lan 

机构地区：[1]Department of Respiratory and Critical Care Medicine,Renmin Hospital of Wuhan University,Wuhan 430060,China [2]Shanghai Key Laboratory of New Drug Design,State Key Laboratory of Bioreactor Engineering,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China [3]State Key Laboratory of Virology,College of Life Sciences,Wuhan University,Wuhan 430072,China [4]Frontier Science Center for Immunology and Metabolism,Wuhan University,Wuhan 430072,China

出　　处：《Virologica Sinica》2020年第6期725-733,共9页中国病毒学（英文版）

基　　金：supported by the Science and Technology Key Project on Novel Coronavirus Pneumonia,Hubei Province(project number:2020FCA002 to K.H.);the Application&Frontier Research Program of Wuhan Government(2019020701011463 to K.X.);Taikang Insurance Group Co.,Ltd;Beijing Taikang Yicai Foundation;Special Fund for COVID-19 Research of Wuhan University for their great supports to this work。

摘　　要：We recently reported that inhibitors against human dihydroorotate dehydrogenase(DHODH)have broad-spectrum antiviral activities including their inhibitory efficacies on SARS-CoV-2 replication in infected cells.However,there are limited data from clinical studies to prove the application of DHODH inhibitors in Coronavirus disease 2019(COVID-19)patients.In the present study,we evaluated Leflunomide,an approved DHODH inhibitor widely used as a modest immune regulator to treat autoimmune diseases,in treating COVID-19 disease with a small-scale of patients.Cases of 10 laboratory-confirmed COVID-19 patients of moderate type with obvious opacity in the lung were included.Five of the patients were treated with Leflunomide,and another five were treated as blank controls without a placebo.All the patients accepted standard supportive treatment for COVID-19.The patients given Leflunomide had a shorter viral shedding time(median of5 days)than the controls(median of 11 days,P=0.046).The patients given Leflunomide also showed a significant reduction in C-reactive protein levels,indicating that immunopathological inflammation was well controlled.No obvious adverse effects were observed in Leflunomide-treated patients,and they all discharged from the hospital faster than controls.This preliminary study on a small-scale compassionate use of Leflunomide provides clues for further understanding of Leflunomide as a potential antiviral drug against COVID-19.

关 键 词：DHODH inhibitors LEFLUNOMIDE Coronavirus disease 2019(COVID-19) Viral shedding time Inflammation 

分 类 号：R969.4[医药卫生—药理学]