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| 1 | Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro显示文摘Dear Editor,In December 2019,a novel pneumonia caused by a previously unknown pathogen emerged in Wuhan,a city of 11 million people in central China.The initial cases were linked to exposures in a seafood market in Wuhan.1 As of January 27,2020,the Chinese authorities reported 2835 confirmed cases in China's Mainland,including 81 deaths.Additionally,19 confirmed cases were identified in Hong Kong,Macao and Taiwan,and 39 imported cases were identified in Thailand,Japan,South Korea,United States,Vietnam,Singapore,Nepal,France,Australia and Canada.The pathogen was soon identified as a novel coronavirus(2019-nCoV),which is closely related to sever acute respiratory syndrome CoV(SARS-CoV).2 Currently,there is no specific treatment against the new virus.Therefore,identifying effective antiviral agents to combat the disease is urgently needed. | Manli Wang Ruiyuan Cao Leike Zhang Xinglou Yang Jia Liu Mingyue Xu Zhengli Shi Zhihong Hu Wu Zhong Gengfu Xiao | 2020 | Cell Research2020，30，3： | 563 |
| 2 | Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2显示文摘Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide,such as the on-going outbreak of the novel coronavirus SARS-CoV-2.Herein,we identified two potent inhibitors of human DHODH,S312 and S416,with favorable drug-likeness and pharmacokinetic profiles,which all showed broad-spectrum antiviral effects against various RNA viruses,including influenza A virus,Zika virus,Ebola virus,and particularly against SARS-CoV-2.Notably,S416 is reported to be the most potent inhibitor so far with an EC5o of 17 nmol/L and an SI value of 10,505.88 in infec-ted cells.Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells.This work demonstrates that both S312/S416 and old drugs(Leflunomide/Teriflunomide)with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide,no matter such viruses are mutated or not. | Rui Xiong Leike Zhang Shiliang Li Yuan Sun Minyi Ding Yong Wang Yongliang Zhao Yan Wu Weijuan Shang Xiaming Jiang Jiwei Shan Zihao Shen Yi Tong Liuxin Xu Yu Chen Yingle Liu Gang Zou Dimitri Lavillete Zhenjiang Zhao Rui Wang Lili Zhu Gengfu Xiao Ke Lan Honglin Li Ke Xu | 2020 | Protein & Cell2020，11，10： | 14 |
| 3 | Design and development of an oral remdesivir derivative W116 against SARS-CoV-2显示文摘Dear Editor,Since the declaration of COVID-19 as a global pandemic on March 11,2020,this pandemic has been circulating for 17 months throughout the world,leading to more than 200 million infections and nearly 4.4 million deaths as of August 15,2021.The pathogen of COVID-19 is a novel coronavirus named SARS-CoV-2,which shares-79%genome sequence identity with SARS-CoV.1 At the early stage of the COVID-19 outbreak,5ARS-CoV-2 caused great panic in the hardest-hit areas due to its high transmissibility and pathogenicity.To fight the COVID-19 crisis,drug repurposing was immediately pursued in order to find potential therapeutics. | Yuanchao Xie Wanchao Yin Yumin Zhang Weijuan Shang Zhen Wang Xiaodong Luan Guanghui Tian Haji A.Aisa Yechun Xu Gengfu Xiao Jia Li Hualiang Jiang Shuyang Zhanq Leike Zhang H.Eric Xu Jingshan Shen | 2021 | Cell Research2021，31，11： | 12 |
| 4 | Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332显示文摘Dear Editor,Since December 2019,the pandemic of coronavirus disease 2019(COVID-19)has taken a heavy toll on global health,creating an urgent need to develop effective strategies for prevention and treatment.The etiological agent,known as severe acute respiratory syndrome coronavirus 2(SARSCoV-2),has infected nearly 229.2 million people worldwide with more than 4.7 million deaths as of September 15,2021.Older age and preexisting health conditions are associated with worse clinical prognosis including higher mortality rates(Zhou et al.,2020).The global race to combat this pandemic has led to rapid deployment of numerous effective vaccines against SARS-CoV-2(Tregoning et al.,2021).However,the emergence of viral variants,including the Delta variant(B.1.617.2),compromised vaccine effectiveness with resurgence of SARS-CoV-2 infection among highly vaccinated population(Keehner et al.,2021).Therefore,development of therapeutics against the more conserved viral targets would be essential to contain the spread of COVID-19 and reduce mortality. | Yao Zhao Chao Fang Qi Zhang Ruxue Zhang Xiangbo Zhao Yinkai Duan Haofeng Wang Yan Zhu Lu Feng Jinyi Zhao Maolin Shao Xiuna Yang Leike Zhang Chao Peng Kailin Yang Dawei Ma Zihe Rao Haitao Yang | 2022 | Protein & Cell2022，13，9： | 6 |
| 5 | SARS-CoV-2-encoded nucleocapsid protein acts as a viral suppressor of RNA interference in cells显示文摘Dear Editor,Coronaviruses (Co Vs) are large enveloped non-segmented positive-strand RNA viruses that broadly distribute among humans and other animal species, including bats, mice and birds. SARS-Co V-2 infections can cause diseases, named the 2019 novel coronavirus disease (COVID-19). The symptoms of COVID-19 range from mild symptoms to severe respiratory syndromes, including pneumonia, and even death(Chen et al., 2020b;Jiang and Shi, 2020;Xia et al., 2020). | Jingfang Mu Jiuyue Xu Leike Zhang Ting Shu Di Wu Muhan Huang Yujie Ren Xufang Li Qing Geng Yi Xu Yang Qiu Xi Zhou | 2020 | Science China(Life Sciences)2020，63，9： | 5 |
| 6 | Structure-function relationship of the mammarenavirus envelope glycoprotein显示文摘Mammarenaviruses, including lethal pathogens such as Lassa virus and Junín virus, can cause severe hemorrhagic fever in humans. Entry is a key step for virus infection, which starts with binding of the envelope glycoprotein(GP) to receptors on target cells and subsequent fusion of the virus with target cell membranes. The GP precursor is synthesized as a polypeptide, and maturation occurs by two cleavage events, yielding a tripartite GP complex(GPC) formed by a stable signal peptide(SSP), GP1 and GP2. The unique retained SSP interacts with GP2 and plays essential roles in virion maturation and infectivity. GP1 is responsible for binding to the cell receptor, and GP2 is a class I fusion protein. The native structure of the tripartite GPC is unknown.GPC is critical for the receptor binding, membrane fusion and neutralization antibody recognition.Elucidating the molecular mechanisms underlining the structure–function relationship of the three subunits is the key for understanding their function and can facilitate novel avenues for combating virus infections. This review summarizes the basic aspects and recent research of the structure–function relationship of the three subunits. We discuss the structural basis of the receptor-binding domain in GP1, the interaction between SSP and GP2 and its role in virion maturation and membrane fusion, as well as the mechanism by which glycosylation stabilizes the GPC structure and facilitates immune evasion. Understanding the molecular mechanisms involved in these aspects will contribute to the development of novel vaccines and treatment strategies against mammarenaviruses infection. | Wei Wang Zheng Zhou Leike Zhang Shaobo Wang Gengfu Xiao | 2016 | Virologica Sinica2016，31，5： | 4 |
| 7 | High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors显示文摘A new coronavirus(SARS-CoV-2)has been identified as the etiologic agent for the COVID-19 outbreak.Currently,effective treatment options remain very limited for this disease;therefore,there is an urgent need to identify new anti-COVID-19 agents.In this study,we screened over 6,000 compounds that included approved drugs,drug candidates in clinical trials,and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease(PLpro).Together with main protease(Mpro),PLpro is responsible for processing the viral replicase polyprotein into functional units.There-fore,it is an attractive target for antiviral drug develop-ment.Here we discovered four compounds,YM155,cryptotanshinone,tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 pmol/L.These compounds also exhibit strong antiviral activities in cell-based assays.YM155,an anti-cancer drug candidate in clinical trials,has the most potent antiviral activity with an EC50 value of 170 nmol/L.In addition,we have determined the crystal structures of this enzyme and its complex with YM155,revealing a unique binding mode.YM155 simultaneously targets three'hot'spots on PLpro,including the substrate-binding pocket,the interferon stimulating gene product 15(ISG15)binding site and zinc finger motif.Our results demonstrate the efficacy of this screening and repur-posing strategy,which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments. | Yao Zhao Xiaoyu Du Yinkai Duan Xiaoyan Pan Yifang Sun Tian You Lin Han Zhenming Jin Weijuan Shang Jing Yu Hangtian Guo Qianying Liu Yan Wu Chao Peng Jun Wang Chenghao Zhu Xiuna Yang Kailin Yang Ying Lei Luke W.Guddat Wenqing Xu Gengfu Xiao Lei Sun Leike Zhang Zihe Rao Haitao Yang | 2021 | Protein & Cell2021，12，11： | 4 |
| 8 | Comprehensive interactome analysis of the spike protein of swine acute diarrhea syndrome coronavirus显示文摘Swine acute diarrhea syndrome coronavirus(SADS‐CoV)is a recently discovered coronavirus that causes severe and acute diarrhea and rapid weight loss in piglets.SADS‐CoV was reported to be capable of infecting cell lines derived from diverse species,including bats,mice,hamsters,rats,chickens,pigs,nonhuman primates,and humans,implying its high risk of cross‐species infection.However,its receptor is still unknown.In this study,the receptor‐binding domain of the SADS‐CoV spike(S)protein was purified and then subjected to affinity purification(AP)‐coupled mass spectrometry(MS)‐based proteomic analysis to identify the interactors of the SADS‐CoV S protein.Forty‐three host proteins were identified,and a Gene Ontology analysis indicated that these interactors can be grouped into categories such as“cell‐cell adhesion”,“translation”“viral transcription”,suggesting that these processes may participate in the SADS‐CoV life cycles.RNA interference‐based screening of these interactors indicated that PPIB and vimentin can affect SADS‐CoV replication.Our study provides an overarching view into the host interactome of the SADS‐CoV S protein and highlights potential targets for the development of therapeutics against SADS‐CoV. | Qingxing Wang Yun Luo Weijuan Shang Zhengli Shi Gengfu Xiao Leike Zhang | 2021 | Biosafety and Health2021，3，3： | 3 |
| 9 | Oral remdesivir derivative VV116 is a potent inhibitor of respiratory syncytial virus with efficacy in mouse model显示文摘Dear Editor,Respiratory syncytial virus(RSV)is the leading cause of serious lower respiratory tract disease in children under 5 years of age worldwide,causing an estimated 3.2 million hospitalizations and 120,000 deaths in children globally per year.Furthermore,nearly all children can be infected with RSV by 2 years of age,and individuals can be repeatedly re-infected with RSV throughout life,which poses great threats to infants,the elderly. | Ruxue Zhang Yumin Zhang Wei Zheng Weijuan Shang Yan Wu Ning Li Jun Xiong Hualiang Jiang Jingshan Shen Gengfu Xiao Yuanchao Xie Leike Zhang | 2022 | Signal Transduction and Targeted Therapy2022，7，5： | 2 |
| 10 | A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir显示文摘During the ongoing pandemic,providing treatment consisting of effective,low-cost oral antiviral drugs at an early stage of SARSCoV-2 infection has been a priority for controling 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 stillimited,resulting in optimized drug development becoming an urgent requirement. | Yumin Zhang Yuan Sun Yuanchao Xie Wejuan Shang Zhen Wang Hualiang Jiang Jingshan Shen Gengfu Xiao Leike Zhang | 2023 | Signal Transduction and Targeted Therapy2023，8，10： | 1 |
| 11 | High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors显示文摘The global COVID-19 coronavirus pandemic has infected over 109 million people,leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment.Here,we screened about 1.8 million small molecules against the main protease(M^(pro))and papain like protease(PL^(pro)),two major proteases in severe acute respiratory syndrome-coronavirus 2 genome,and identified 1851M^(pro)inhibitors and 205 PL^(pro)inhibitors with low nmol/l activity of the best hits.Among these inhibitors,eight small molecules showed dual inhibition effects on both M^(pro)and PL^(pro),exhibiting potential as better candidates for COVID-19 treatment.The best inhibitors of each protease were tested in antiviral assay,with over 40%of M^(pro)inhibitors and over 20%of PL^(pro)inhibitors showing high potency in viral inhibition with low cytotoxicity.The X-ray crystal structure of SARS-CoV-2 M^(pro)in complex with its potent inhibitor 4a was determined at 1.8Åresolution.Together with docking assays,our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development. | Yi Zang Mingbo Su Qingxing Wang Xi Cheng Wenru Zhang Yao Zhao Tong Chen Yingyan Jiang Qiang Shen Juan Du Qiuxiang Tan Peipei Wang Lixin Gao Zhenming Jin Mengmeng Zhang Cong Li Ya Zhu Bo Feng Bixi Tang Han Xie Ming-Wei Wang Mingyue Zheng Xiaoyan Pan Haitao Yang Yechun Xu Beili Wu Leike Zhang Zihe Rao Xiuna Yang Hualiang Jiang Gengfu Xiao Qiang Zhao Jia Li | 2023 | Protein & Cell2023，14，1： | 0 |
| 12 | Correction: Discovery of novel non-peptidic and non-covalent small-molecule 3CL^(pro) inhibitors as potential candidate for COVID-19 treatment显示文摘In our recent review of the article[1],the author noticed that the dots(red squares)in Fig 1m were accidentally removed from its original location during figure formatting,and the related data analysis is correct.Furthermore,we checked this paper again and this situation only occurred in Fig 1m.In addition,in Fig 1c,a legend for SARS-CoV-1 is missing and we have supplemented it.For the text section,no modifications are required.The correct data are provided as follows.The key findings of the article are not affected by these corrections.The original article has been corrected.We regret any inconvenience this has caused. | Zhidong Jiang Bo Feng Yumin Zhang Tianqing Nie Hong Liu Jia Li Haixia Su Leike Zhang Yi Zang Yu Zhou | 2023 | Signal Transduction and Targeted Therapy2023，8，11： | 0 |
| 13 | Discovery of novel non-peptidic and non-covalent small-molecule 3CL^(pro)inhibitors as potential candidate for COVID-19 treatment显示文摘Dear Editor,The global coronavirus disease 2019(COVID-19)pandemic,which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has brought a profound impact on humanity.SARS-CoV-2 enters host cells through the interaction of its spike glycoprotein with angiotensin-converting enzyme 2(ACE2)of the host and releases its viral RNA genome.^(1) | Zhidong Jiang Bo Feng Yumin Zhang Tianqing Nie Hong Liu Jia Li Haixia Su Leike Zhang Yi Zang Yu Zhou | 2023 | Signal Transduction and Targeted Therapy2023，8，6： | 0 |
| 14 | Correction to:Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2显示文摘CORRECTION TO:PROTEIN CELL 2020,11(10):723–739 http://gffzzd3cc09b8251d45dfox6pkuww5o5fn60on.ffgz.tsg.suse.edu.cn/10.1007/S13238-020-00768-W In the original publication the author’s name‘Dimitri Lavillete’is published incorrectly.The correct author name should be spelt as‘Dimitri Lavillette’is provided in this correction.OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article's Creative Commons licence,unless indicated otherwise in a credit line to the material.If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.To view a copy of this licence,visit http://gffzzeb6f7f563f66445dhx6pkuww5o5fn60on.ffgz.tsg.suse.edu.cn/licenses/by/4.0/. | Rui Xiong Leike Zhang Shiliang Li Yuan Sun Minyi Ding Yong Wang Yongliang Zhao Yan Wu Weijuan Shang Xiaming Jiang Jiwei Shan Zihao Shen Yi Tong Liuxin Xu Yu Chen Yingle Liu Gang Zou Dimitri Lavillette Zhenjiang Zhao Rui Wang Lili Zhu Gengfu Xiao Ke Lan Honglin Li Ke Xu | 2022 | Protein & Cell2022，13，10： | 0 |
| 15 | Correction to: Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2显示文摘Figure 1.Discovery of novel and potent DHODHi and their anti-influenza A virus activities.(A)The discovery and design of S312 and S416.The detailed descriptions of the discovery workflow are in Method.Binding analysis of S312(B)and S416(C).Thermodynamic analysis of the binding of S312 and S416 to DHODH was carried out at 25 C on a MicroCal iTC200 instrument.Kinetic analysis of the binding of S312 and S416 to DHODH was performed with a Biacore T200 instrument. | Rui Xiong Leike Zhang Shiliang Li Yuan Sun Minyi Ding Yong Wang Yongliang Zhao Yan Wu Weijuan Shang Xiaming Jiang Jiwei Shan Zihao Shen Yi Tong Liuxin Xu Yu Chen Yingle Liu Gang Zou Dimitri Lavillete Zhenjiang Zhao Rui Wang Lili Zhu Gengfu Xiao Ke Lan Honglin Li Ke Xu | 2021 | Protein & Cell2021，12，1： | 0 |
| 16 | Comparative Antiviral Efficacy of Viral Protease Inhibitors against the Novel SARS-CoV-2 In Vitro显示文摘The recent outbreak of novel coronavirus pneumonia(COVID-19)caused by a new coronavirus has posed a great threat to public health.Identifying safe and effective antivirals is of urgent demand to cure the huge number of patients.Virusencoded proteases are considered potential drug targets.The human immunodeficiency virus protease inhibitors(lopinavir/ritonavir)has been recommended in the global Solidarity Trial in March launched by World Health Organization.However,there is currently no experimental evidence to support or against its clinical use.We evaluated the antiviral efficacy of lopinavir/ritonavir along with other two viral protease inhibitors in vitro,and discussed the possible inhibitory mechanism in silico.The in vitro to in vivo extrapolation was carried out to assess whether lopinavir/ritonavir could be effective in clinical.Among the four tested compounds,lopinavir showed the best inhibitory effect against the novel coronavirus infection.However,further in vitro to in vivo extrapolation of pharmacokinetics suggested that lopinavir/ritonavir could not reach effective concentration under standard dosing regimen[marketed as Kaletraò,contained lopinavir/ritonavir(200 mg/50 mg)tablets,recommended dosage is 400 mg/10 mg(2 tablets)twice daily].This research concluded that lopinavir/ritonavir should be stopped for clinical use due to the huge gap between in vitro IC50 and free plasma concentration.Nevertheless,the structure–activity relationship analysis of the four inhibitors provided further information for de novel design of future viral protease inhibitors of SARS-CoV-2. | Leike Zhang Jia Liu Ruiyuan Cao Mingyue Xu Yan Wu Weijuan Shang Xi Wang Huanyu Zhang Xiaming Jiang Yuan Sun Hengrui Hu Yufeng Li Gang Zou Min Zhang Lei Zhao Wei Li Xiaojia Guo Xiaomei Zhuang Xing-Lou Yang Zheng-Li Shi Fei Deng Zhihong Hu Gengfu Xiao Manli Wang Wu Zhong | 2020 | Virologica Sinica2020，35，6： | 0 |
| 17 | Structure basis for allosteric regulation of lymphocytic choriomeningitis virus polymerase function by Z matrix protein显示文摘DearEditor,The Arenaviridae family(recently assigned to the Bunyavirales order)is a group of emerging viruses that include causative agents of severe hemorrhagic fevers with high mortality in humans(de la Torre,2009).Lymphocytic choriomeningitis virus(LCMV)is the prototypic member of the Arenaviridae family and belongs to the Old World(OW)arenavirus together with Lassa virus(LASV),which are distinct from the New World(NW)arenavirus[e.g.Machupo virus(MACV)and Junin virus(JUNV)].LCMV infection in the fetus and newborm results in severe impairment of brain development associated with sensory loss and mental retardation and is also known to be associated with severe systemic infection with high mortality in transplantation patients(Palacios et al.,2008). | Lu Liu Panpan Wang Aijun Liu Leike Zhang Liming Yan Yu Guo Gengfu Xiao Zihe Rao Zhiyong Lou | 2023 | Protein & Cell2023，14，9： | 0 |
| 18 | Hsp90βis critical for the infection of severe fever with thrombocytopenia syndrome virus显示文摘Severe fever with thrombocytopenia syndrome(SFTS)caused by the SFTS virus(SFTSV)is an emerging disease in East Asia with a fatality rate of up to 30%.However,the viral-host interaction of SFTSV remains largely unknown.The heat-shock protein 90(Hsp90)family consists of highly conserved chaperones that fold and remodel proteins and has a broad impact on the infection of many viruses.Here,we showed that Hsp90 is an important host factor involved in SFTSV infection.Hsp90 inhibitors significantly reduced SFTSV replication,viral protein expression,and the formation of inclusion bodies consisting of nonstructural proteins(NSs).Among viral proteins,NSs appeared to be the most reduced when Hsp90 inhibitors were used,and further analysis showed that their translation was affected.Co-immunoprecipitation of NSs with four isomers of Hsp90 showed that Hsp90βspecifically interacted with them.Knockdown of Hsp90βexpression also inhibited replication of SFTSV.These results suggest that Hsp90βplays a critical role during SFTSV infection and could be a potential target for the development of drugs against SFTS. | Bo Wang Leike Zhang Fei Deng Zhihong Hu Manli Wang Jia Liu | 2024 | Virologica Sinica2024，39，1： | 0 |
| 19 | Identification of proteasome and caspase inhibitors targeting SARS-CoV-2 Mpro显示文摘Dear Editor,Since the beginning of 2020,the Coronavirus(CoV)Disease 2019(COVID-19)pandemic has posed formidable challenges to public health security.The main protease(Mpro,3CLpro)of CoVs plays essential roles in viral replication,making them attractive targets for antiviral drug development. | Zhengyuan Wang Yao Zhao Qingxing Wang Yangfei Xing Lu Feng Juan Kong Chao Peng Leike Zhang Haitao Yang Min Lu | 2021 | Signal Transduction and Targeted Therapy2021，6，7： | 0 |
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