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A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir

文献类型：期刊论文

作者Zhang, Yumin5; Sun, Yuan4,5; Xie, Yuanchao1; Shang, Weijuan5; Wang, Zhen1; Jiang, Hualiang1,3; Shen, Jingshan3,4; Xiao, Gengfu4,5; Zhang, Leike2,4,5
刊名SIGNAL TRANSDUCTION AND TARGETED THERAPY
出版日期2023-09-22
卷号8期号:1页码:10
ISSN号2095-9907
DOI10.1038/s41392-023-01587-1
通讯作者Shen, Jingshan(shenjingshan@simm.ac.cn) ; Xiao, Gengfu(xiaogf@wh.iov.cn) ; Zhang, Leike(zhangleike@wh.iov.cn)
英文摘要During the ongoing pandemic, providing treatment consisting of effective, low-cost oral antiviral drugs at an early stage of SARS-CoV-2 infection has been a priority for controlling COVID-19. Although Paxlovid and molnupiravir have received emergency approval from the FDA, some side effect concerns have emerged, and the possible oral agents are still limited, resulting in optimized drug development becoming an urgent requirement. An oral remdesivir derivative, VV116, has been reported to have promising antiviral effects against SARS-CoV-2 and positive therapeutic outcomes in clinical trials. However, whether VV116 has broad-spectrum anti-coronavirus activity and potential synergy with other drugs is not clear. Here, we uncovered the broad-spectrum antiviral potency of VV116 against SARS-CoV-2 variants of concern (VOCs), HCoV-OC43, and HCoV-229E in various cell lines. In vitro drug combination screening targeted RdRp and proteinase, highlighting the synergistic effect of VV116 and nirmatrelvir on HCoV-OC43 and SARS-CoV-2. When co-administrated with ritonavir, the combination of VV116 and nirmatrelvir showed significantly enhanced antiviral potency with noninteracting pharmacokinetic properties in mice. Our findings will facilitate clinical treatment with VV116 or VV116+nirmatrelvir combination to fight coronavirus infection.
WOS关键词ANTIVIRAL ACTIVITY ; DRUG-COMBINATIONS ; OC43
资助项目We thank Tao Du, Hao Tang, Jia Wu, and Jun Liu from BSL-3 Laboratory of Wuhan Institute of Virology for their critical support. We thank Xuefang An and Ding Gao in the Core Facility and Technical Support Facility of the Wuhan Institute of Virology for thei[U22A20379] ; We thank Tao Du, Hao Tang, Jia Wu, and Jun Liu from BSL-3 Laboratory of Wuhan Institute of Virology for their critical support. We thank Xuefang An and Ding Gao in the Core Facility and Technical Support Facility of the Wuhan Institute of Virology for thei[31970165] ; National Natural Science Foundation of China[2021YFC2300700] ; National Natural Science Foundation of China[2022YFC2303300] ; National Key Research and Development Plan of China[2022000025] ; Special Foundation of the Chinese Academy of Sciences[21S11903100] ; Shanghai Science and Technology Committee in China
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者SPRINGERNATURE
WOS记录号WOS:001071173200002
源URL[http://119.78.100.183/handle/2S10ELR8/307155]  
专题中国科学院上海药物研究所
通讯作者Shen, Jingshan; Xiao, Gengfu; Zhang, Leike
作者单位1.Lingang Lab, Shanghai 200031, Peoples R China
2.Hubei Jiangxia Lab, Wuhan 430200, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Chinese Acad Sci, State Key Lab Virol, Wuhan Inst Virol, Ctr Biosafety Mega Sci, Wuhan 430071, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Yumin,Sun, Yuan,Xie, Yuanchao,et al. A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2023,8(1):10.
APA Zhang, Yumin.,Sun, Yuan.,Xie, Yuanchao.,Shang, Weijuan.,Wang, Zhen.,...&Zhang, Leike.(2023).A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir.SIGNAL TRANSDUCTION AND TARGETED THERAPY,8(1),10.
MLA Zhang, Yumin,et al."A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir".SIGNAL TRANSDUCTION AND TARGETED THERAPY 8.1(2023):10.

入库方式： OAI收割

来源：上海药物研究所

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