Volume 11 Issue 10
Sep.  2020
Turn off MathJax
Article Contents
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. Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2[J]. Protein&Cell, 2020, 11(10): 723-739. doi: 10.1007/s13238-020-00768-w
Citation: 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. Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2[J]. Protein&Cell, 2020, 11(10): 723-739. doi: 10.1007/s13238-020-00768-w

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

doi: 10.1007/s13238-020-00768-w

This work was supported in part by the National Key Research and Development Program Grants (2018FYA0900801 and 2018ZX10101004003001 to K.X., 2016YFA0502304 to H.L.), the National Natural Science Foundation of China (Grants 31922004 and 81772202 to K.X., 81825020 to H.L.), the National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program” of China (Grant 2018ZX09711002 to H.L.), Application & Frontier Research Program of Wuhan Government (2019020701011463 to K.X.).

  • Received Date: 2020-06-29
  • Rev Recd Date: 2020-07-05
  • Publish Date: 2020-09-27
  • 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 broadspectrum 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 EC50 of 17 nmol/L and an SI value of 10,505.88 in infected 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.
  • loading
  • [1]
    Adalja A, Inglesby T (2019) Broad-spectrum antiviral agents:a crucial pandemic tool. Expert Rev Anti Infect Ther 17:467-470
    Adcock RS, Chu YK, Golden JE, Chung DH (2017) Evaluation of anti-Zika virus activities of broad-spectrum antivirals and NIH clinical collection compounds using a cell-based, high-throughput screen assay. Antiviral Res 138:47-56
    Carroll T, Lo M, Lanteri M, Dutra J, Zarbock K, Silveira P, Rourke T, Ma Z-M, Fritts L, O'Connor S (2017) Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques. PLoS Pathog 13:e1006537
    Chen SF, Perrella FW, Behrens DL, Papp LM (1992) Inhibition of dihydroorotate dehydrogenase activity by brequinar sodium. Cancer Res 52:3521-3527
    Chen S, Ding S, Yin Y, Xu L, Li P, Peppelenbosch MP, Pan Q, Wang W (2019) Suppression of pyrimidine biosynthesis by targeting DHODH enzyme robustly inhibits rotavirus replication. Antiviral Res 167:35-44
    Chen L, Liu W, Zhang Q, Xu K, Ye G, Wu W, Sun Z, Liu F, Wu K, Zhong B et al (2020) RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak. Emerg Microbes Infect 9:313-319
    Cheung NN, Lai KK, Dai J, Kok KH, Chen H, Chan K-H, Yuen K-Y, Kao RYT (2017) Broad-spectrum inhibition of common respiratory RNA viruses by a pyrimidine synthesis inhibitor with involvement of the host antiviral response. J Gen Virol 98:946-954
    Chien JY, Hsueh PR, Cheng WC, Yu CJ, Yang PC (2006) Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome. Respirology 11(6):715-722
    Chung D-H, Golden JE, Adcock RS, Schroeder CE, Chu Y-K, Sotsky JB, Cramer DE, Chilton PM, Song C, Anantpadma M (2016) Discovery of a broad-spectrum antiviral compound that inhibits pyrimidine biosynthesis and establishes a type 1 interferon-independent antiviral state. Antimicrob Agents Chemother 60:4552-4562
    Coelho FC, Durovni B, Saraceni V, Lemos C, Codeco CT, Camargo S, De Carvalho LM, Bastos L, Arduini D, Villela DA (2016) Higher incidence of Zika in adult women than adult men in Rio de Janeiro suggests a significant contribution of sexual transmission from men to women. Int J Infect Dis 51:128-132
    Collaborative CP (1994) The CCP4 suite:programs for protein crystallography. Acta Crystallogr Sect D 50:760
    Das P, Deng X, Zhang L, Roth MG, Fontoura BM, Phillips MA, De Brabander JK (2013) SAR-based optimization of a 4-quinoline carboxylic acid analogue with potent antiviral activity. ACS Med Chem Lett 4:517-521
    Davies B, Morris T (1993) Physiological parameters in laboratory animals and humans. Pharm Res 10:1093-1095
    Debing Y, Neyts J, Delang L (2015) The future of antivirals:broad-spectrum inhibitors. Curr Opin Infect Dis 28:596-602
    Deng C, Liu S, Zhang Q, Xu M, Zhang H, Gu D, Shi L, He J, Xiao G, Zhang B (2016) Isolation and characterization of Zika virus imported to China using C6/36 mosquito cells. Virol Sin 31:176-179
    Diao YY, Lu WQ, Jin HT, Zhu JS, Han L, Xu MH, Gao R, Shen X, Zhao ZJ, Liu XF et al (2012) Discovery of diverse human dihydroorotate dehydrogenase inhibitors as immunosuppressive agents by structure-based virtual screening. J Med Chem 55:8341-8349
    Emsley P, Lohkamp B, Scott WG, Cowtan K (2010) Features and development of Coot. Acta Crystallogr Sect D 66:486-501
    Evans P (2006) Scaling and assessment of data quality. Acta Crystallogr Sect D 62:72-82
    Fox RI, Herrmann ML, Frangou CG, Wahl GM, Morris RE, Strand V, Kirschbaum BJ (1999) Mechanism of action for leflunomide in rheumatoid arthritis. Clin Immunol 93:198-208
    Gao GF (2018) From "A" IV to "Z" IKV:attacks from emerging and re-emerging pathogens. Cell 172:1157-1159
    Gao HN, Lu HZ, Cao B, Du B, Shang H, Gan JH, Lu SH, Yang YD, Fang Q, Shen YZ (2013) Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med 368:2277-2285
    Grandin C, Hourani M-L, Janin YL, Dauzonne D, Munier-Lehmann H, Paturet A, Taborik F, Vabret A, Contamin H, Tangy F (2016) Respiratory syncytial virus infection in macaques is not suppressed by intranasal sprays of pyrimidine biosynthesis inhibitors. Antiviral Res 125:58-62
    Han Q, Chang C, Li L, Klenk C, Cheng J, Chen Y, Xia N, Shu Y, Chen Z, Gabriel G et al (2014) Sumoylation of influenza A virus nucleoprotein is essential for intracellular trafficking and virus growth. J Virol 88:9379-9390
    Harvey R, Brown K, Zhang Q, Gartland M, Walton L, Talarico C, Lawrence W, Selleseth D, Coffield N, Leary J et al (2009) GSK983:a novel compound with broad-spectrum antiviral activity. Antiviral Res 82:1-11
    Hoffmann H-H, Kunz A, Simon VA, Palese P, Shaw ML (2011) Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis. Proc Natl Acad Sci 108:5777-5782
    Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X et al (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 395:497-506
    Hung I, To K, Lee C, Lee K, Yan W, Chan K, Ngai C, Law K, Chow F, Liu R (2013) Hyperimmune intravenous immunoglobulin treatment:a multicentre double-blind randomized controlled trial for patients with severe A(H1N1)pdm09 infection. Chest 144:464-473
    Ianevski A, Andersen PI, Merits A, Bjørås M, Kainov D (2019) Expanding the activity spectrum of antiviral agents. Drug Discov Today 24:1224-1228
    Jasenosky LD, Neumann G, Kawaoka Y (2010) Minigenome-based reporter system suitable for high-throughput screening of compounds able to inhibit ebolavirus replication and/or transcription. Antimicrob Agents Chemother 54:3007
    Jordan PC, Stevens SK, Deval J (2018) Nucleosides for the treatment of respiratory RNA virus infections. Antiviral Chem Chemother 26:1-19
    Jordheim LP, Durantel D, Zoulim F, Dumontet C (2013) Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat Rev Drug Discov 12:447-464
    Kottkamp AC, De Jesus E, Grande R, Brown JA, Jacobs AR, Lim JK, Stapleford KA (2019) Atovaquone inhibits arbovirus replication through the depletion of intracellular nucleotides. J Virol 93:e00389-00319
    Li S, Luan G, Ren X, Song W, Xu L, Xu M, Zhu J, Dong D, Diao Y, Liu X et al (2015) Rational design of benzylidenehydrazinyl-substituted thiazole derivatives as potent inhibitors of human dihydroorotate dehydrogenase with in vivo anti-arthritic activity. Sci Rep 5:14836
    Liu Z, Guo Z, Wang G, Zhang D, He H, Li G, Liu Y, Higgins D, Walsh A, Shanahan-Prendergast L (2009) Evaluation of the efficacy and safety of a statin/caffeine combination against H5N1, H3N2 and H1N1 virus infection in BALB/c mice. Eur J Pharm Sci 38:215-223
    Lucas-Hourani M, Dauzonne D, Jorda P, Cousin G, Lupan A, Helynck O, Caignard G, Janvier G, André-Leroux G, Khiar S (2013) Inhibition of pyrimidine biosynthesis pathway suppresses viral growth through innate immunity. PLoS Pathog 9:e1003678
    Lucas-Hourani M, Dauzonne D, Munier-Lehmann H, Khiar S, Nisole S, Dairou J, Helynck O, Afonso PV, Tangy F, Vidalain P-O (2017) Original chemical series of pyrimidine biosynthesis inhibitors that boost the antiviral interferon response. Antimicrob Agents Chemother 61:e00383-00317
    Luke TC, Kilbane EM, Jackson JL, Hoffman SL (2006) Meta-analysis:convalescent blood products for spanish influenza pneumonia:a future H5N1 Treatment? Ann Intern Med 145:599-609
    Luthra P, Naidoo J, Pietzsch CA, De S, Khadka S, Anantpadma M, Williams CG, Edwards MR, Davey RA, Bukreyev A (2018) Inhibiting pyrimidine biosynthesis impairs Ebola virus replication through depletion of nucleoside pools and activation of innate immune responses. Antiviral Res 158:288-302
    Marschall M, Niemann I, Kosulin K, Bootz A, Wagner S, Dobner T, Herz T, Kramer B, Leban J, Vitt D (2013) Assessment of drug candidates for broad-spectrum antiviral therapy targeting cellular pyrimidine biosynthesis. Antiviral Res 100:640-648
    Matrosovich M, Matrosovich T, Garten W, Klenk H-D (2006) New low-viscosity overlay medium for viral plaque assays. Virol J 3:63
    Matsuoka Y, Lamirande EW, Subbarao K (2009) The mouse model for influenza. Curr Protoc Microbiol 13:15G-3
    McNicholl IR, McNicholl JJ (2001) Neuraminidase inhibitors:zanamivir and oseltamivir. Ann Pharmacother 35:57-70
    Mei-jiao G, Shi-fang L, Yan-yan C, Jun-jun S, Yue-feng S, Ting-ting R, Yong-guang Z, Hui-yun C (2019) Antiviral effects of selected IMPDH and DHODH inhibitors against foot and mouth disease virus. Biomed Pharmacother 118:109305
    Min JY, Subbarao K (2010) Cellular targets for influenza drugs. Nat Biotechnol 28:239-240
    Munier-Lehmann H, Vidalain PO, Tangy F, Janin YL (2013) On dihydroorotate dehydrogenases and their inhibitors and uses. J Med Chem 56:3148-3167
    Murshudov GN, Skubák P, Lebedev AA, Pannu NS, Steiner RA, Nicholls RA, Winn MD, Long F, Vagin AA (2011) REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr Sect D 67:355-367
    Qing M, Zou G, Wang Q-Y, Xu HY, Dong H, Yuan Z, Shi P-Y (2010) Characterization of dengue virus resistance to brequinar in cell culture. Antimicrob Agents Chemother 54:3686-3695
    Raveh A, Delekta PC, Dobry CJ, Peng W, Schultz PJ, Blakely PK, Tai AW, Matainaho T, Irani DN, Sherman DH (2013) Discovery of potent broad spectrum antivirals derived from marine actinobacteria. PLoS ONE 8:e82318
    Rozman B (2002) Clinical pharmacokinetics of leflunomide. Clin Pharmacokinet 41:421-430
    Song W, Li S, Tong Y, Wang J, Quan L, Chen Z, Zhao Z, Xu Y, Zhu L, Qian X et al (2016) Structure-based design of potent human dihydroorotate dehydrogenase inhibitors as anticancer agents. Med Chem Commun 7:1441-1448
    Tang WW, Young MP, Mamidi A, Regla-Nava JA, Kim K, Shresta S (2016) A mouse model of Zika virus sexual transmission and vaginal viral replication. Cell Rep 17:3091-3098
    Van Hoecke L, Job ER, Saelens X, Roose K (2017) Bronchoalveolar lavage of murine lungs to analyze inflammatory cell infiltration. JoVE 123:e55398
    Wan S, Yi Q, Fan S, Lv J, Zhang X, Guo L, Lang C, Xiao Q, Xiao K, Yi Z et al (2020) Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). medRxiv
    Wang CH, Liu C-Y, Wan Y-L, Chou C-L, Huang K-H, Lin H-C, Lin S-M, Lin T-Y, Chung KF, Kuo H-P (2005) Persistence of lung inflammation and lung cytokines with high-resolution CT abnormalities during recovery from SARS. Respir Res 6:42
    Wang QY, Bushell S, Qing M, Xu HY, Bonavia A, Nunes S, Zhou J, Poh MK, Florez de Sessions P, Niyomrattanakit P et al (2011) Inhibition of dengue virus through suppression of host pyrimidine biosynthesis. J Virol 85:6548-6556
    Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G (2020) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 30:269-271
    Wong CK, Lam CWK, Wu AKL, Ip WK, Lee NLS, Chan IHS, Sung JJY (2004) Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol 136:95-103
    Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, Hu Y, Tao ZW, Tian JH, Pei YY et al (2020) A new coronavirus associated with human respiratory disease in China. Nature 579:265-269
    Yang Y, Cao L, Gao H, Wu Y, Wang Y, Fang F, Lan T, Lou Z, Rao Y (2019) Discovery, optimization, and target identification of novel potent broad-spectrum antiviral inhibitors. J Med Chem 62:4056-4073
    Yokota S (2003) Influenza-associated encephalopathy-pathophysiology and disease mechanisms. Jpn J Clin Med 61:1953-1958
    Yuen KY, Wong SS (2005) Human infection by avian influenza A H5N1. Hong Kong Med J 11:189-199
    Zeng H, Waldman WJ, Yin DP, Knight DA, Shen J, Ma L, Meister GT, Chong AS, Williams JW (2005) Mechanistic study of malononitrileamide FK778 in cardiac transplantation and CMV infection in rats. Transplantation 79:17-22
    Zhang Y, Li J, Zhan Y, Wu L, Yu X, Zhang W, Ye L, Xu S, Sun R, Wang Y (2004) Analysis of serum cytokines in patients with severe acute respiratory syndrome. Infect Immun 72:4410-4415
    Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL et al (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579:270-273
    Zhu J, Han L, Diao Y, Ren X, Xu M, Xu L, Li S, Li Q, Dong D, Huang J et al (2015a) Design, synthesis, X-ray crystallographic analysis, and biological evaluation of thiazole derivatives as potent and selective inhibitors of human dihydroorotate dehydrogenase. J Med Chem 58:1123-1139
    Zhu JD, Meng W, Wang XJ, Wang HC (2015b) Broad-spectrum antiviral agents. Front Microbiol 6:517
  • Relative Articles

    [1] Fei Feng,  Yunkai Zhu,  Yanlong Ma,  Yuyan Wang,  Yin Yu,  Xinran Sun,  Yuanlin Song,  Zhugui Shao,  Xinxin Huang,  Ying Liao,  Jingyun Ma,  Yuping He,  Mingyuan Wang,  Longhai Tang,  Yaowei Huang,  Jincun Zhao,  Qiang Ding,  Youhua Xie,  Qiliang Cai,  Hui Xiao,  Chun Li,  Zhenghong Yuan,  Rong Zhang. A CRISPR activation screen identifies genes that enhance SARS-CoV-2 infection. Protein&Cell, 2023, 14(1): 64-68.  doi: 10.1093/procel/pwac036
    [2] Daming Zuo,  Yu Chen,  Jian-piaoCai,  Hao-Yang Yuan,  Jun-Qi Wu,  Yue Yin,  Jing-Wen Xie,  Jing-Min Lin,  Jia Luo,  Yang Feng,  Long-Jiao Ge,  Jia Zhou,  Ronald J. Quinn,  San-Jun Zhao,  Xing Tong,  Dong-Yan Jin,  Shuofeng Yuan,  Shao-Xing Dai,  Min Xu. A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo. Protein&Cell, 2023, 14(1): 37-50.  doi: 10.1093/procel/pwac027
    [3] Simeng Zhao,  Fengjiang Liu,  Shizhen Qiu,  Qiaoshuai Lan,  Yiran Wu,  Wei Xu,  Junzi Ke,  Jie Yang,  Xiaoyan Liu,  Kun Wang,  Hangtian Guo,  Shuai Xia,  Fangfang Zhang,  Jiabei Wang,  Xiaowen Hu,  Lu Lu,  Shibo Jiang,  Suwen Zhao,  Lianxin Liu,  Youhua Xie,  Xiuna Yang,  Haopeng Wang,  Guisheng Zhong. A core epitope targeting antibody of SARS-CoV-2. Protein&Cell, 2023, 14(1): 74-78.  doi: 10.1093/procel/pwac042
    [4] 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. High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors. Protein&Cell, 2023, 14(1): 17-27.  doi: 10.1093/procel/pwac016
    [5] 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. Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332. Protein&Cell, 2022, 13(9): 689-693.  doi: 10.1007/s13238-021-00883-2
    [6] 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. Correction to: Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2. Protein&Cell, 2022, 13(10): 778-778.  doi: 10.1007/s13238-020-00801-y
    [7] Zezhong Liu,  Wei Xu,  Zhenguo Chen,  Wangjun Fu,  Wuqiang Zhan,  Yidan Gao,  Jie Zhou,  Yunjiao Zhou,  Jianbo Wu,  Qian Wang,  Xiang Zhang,  Aihua Hao,  Wei Wu,  Qianqian Zhang,  Yaming Li,  Kaiyue Fan,  Ruihong Chen,  Qiaochu Jiang,  Christian T. Mayer,  Till Schoofs,  Youhua Xie,  Shibo Jiang,  Yumei Wen,  Zhenghong Yuan,  Kang Wang,  Lu Lu,  Lei Sun,  Qiao Wang. An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope. Protein&Cell, 2022, 13(9): 655-675.  doi: 10.1007/s13238-021-00871-6
    [8] Yichen Li,  Shuaiyao Lu,  Jinge Gu,  Wencheng Xia,  Shengnan Zhang,  Shenqing Zhang,  Yan Wang,  Chong Zhang,  Yunpeng Sun,  Jian Lei,  Cong Liu,  Zhaoming Su,  Juntao Yang,  Xiaozhong Peng,  Dan Li. SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation. Protein&Cell, 2022, 13(8): 602-614.  doi: 10.1007/s13238-022-00905-7
    [9] Chun-Chun Gao,  Man Li,  Wei Deng,  Chun-Hui Ma,  Yu-Sheng Chen,  Yong-Qiao Sun,  Tingfu Du,  Qian-Lan Liu,  Wen-Jie Li,  Bing Zhang,  Lihong Sun,  Si-Meng Liu,  Fengli Li,  Feifei Qi,  Yajin Qu,  Xinyang Ge,  Jiangning Liu,  Peng Wang,  Yamei Niu,  Zhiyong Liang,  Yong-Liang Zhao,  Bo Huang,  Xiao-Zhong Peng,  Ying Yang,  Chuan Qin,  Wei-Min Tong,  Yun-Gui Yang. Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques. Protein&Cell, 2022, 13(12): 920-939.  doi: 10.1007/s13238-022-00915-5
    [10] Hang-Yu Zhou,  Cheng-Yang Ji,  Hang Fan,  Na Han,  Xiao-Feng Li,  Aiping Wu,  Cheng-Feng Qin. Convergent evolution of SARS-CoV-2 in human and animals. Protein&Cell, 2021, 12(11): 832-835.  doi: 10.1007/s13238-021-00847-6
    [11] Xingdong Zhou,  Hui Wang,  Qun Ji,  Mingjuan Du,  Yuexia Liang,  Huanhuan Li,  Fan Li,  Hang Shang,  Xiujuan Zhu,  Wei Wang,  Lichun Jiang,  Alexey V. Stepanov,  Tianyu Ma,  Nanxin Gong,  Xiaodong Jia,  Alexander G. Gabibov,  Zhiyong Lou,  Yinying Lu,  Yu Guo,  Hongkai Zhang,  Xiaoming Yang. Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine. Protein&Cell, 2021, 12(10): 818-823.  doi: 10.1007/s13238-021-00840-z
    [12] 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. Correction to: Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2. Protein&Cell, 2021, 12(1): 76-80.  doi: 10.1007/s13238-020-00792-w
    [13] Rongjuan Pei,  Jianqi Feng,  Yecheng Zhang,  Hao Sun,  Lian Li,  Xuejie Yang,  Jiangping He,  Shuqi Xiao,  Jin Xiong,  Ying Lin,  Kun Wen,  Hongwei Zhou,  Jiekai Chen,  Zhili Rong,  Xinwen Chen. Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection. Protein&Cell, 2021, 12(9): 717-733.  doi: 10.1007/s13238-020-00811-w
    [14] 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. High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors. Protein&Cell, 2021, 12(11): 876-887.  doi: 10.1007/s13238-021-00836-9
    [15] Hua Qin,  Andong Zhao. Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics. Protein&Cell, 2020, 11(10): 707-722.  doi: 10.1007/s13238-020-00738-2
    [16] Qing-Yan Guo,  Long-Hua Zhang,  Chao Zuo,  Dong-Liang Huang,  Zhipeng A. Wang,  Ji-Shen Zheng,  Chang-Lin Tian. Channel activity of mirror-image M2 proton channel of influenza A virus is blocked by achiral or chiral inhibitors. Protein&Cell, 2019, 10(3): 211-216.  doi: 10.1007/s13238-018-0536-5
    [17] Mohsan Ullah Goraya,  Song Wang,  Muhammad Munir,  Ji-Long Chen. Induction of innate immunity and its perturbation by influenza viruses. Protein&Cell, 2015, 6(10): 712-721.  doi: 10.1007/s13238-015-0191-z
    [18] Yipeng Sun,  Jinhua Liu. H9N2 influenza virus in China: a cause of concern. Protein&Cell, 2015, 6(1): 18-25.  doi: 10.1007/s13238-014-0111-7
    [19] Jing Qi,  Danyang Gong,  Hongyu Deng. CCAAT/enhancer binding proteins play a role in oriLyt-dependent genome replication during MHV-68 de novo infection. Protein&Cell, 2011, 2(6): 463-469.  doi: 10.1007/s13238-011-1060-z
    [20] Yi Guan,  Dhanasekaran Vijaykrishna,  Justin Bahl,  Huachen Zhu,  Jia Wang,  Gavin J. D. Smith. The emergence of pandemic influenza viruses. Protein&Cell, 2010, 1(1): 9-13.  doi: 10.1007/s13238-010-0008-z
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索


    Article Metrics

    Article views (1745) PDF downloads(370) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint