Login Register Cart 0
Review Article

新型冠状病毒主要蛋白酶(Mpro)和RdRp靶点的研究

卷 23, 期 8, 2022

发表于: 06 September, 2021

页: [802 - 817] 页: 16

弟呕挨: 10.2174/1389450122666210906154849

价格: $65

摘要

由新型严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2)株引起的前所未有的COVID-19大流行在全世界吞噬了数百万人的死亡。它直接影响到受影响国家的社会经济地位。有超过219个国家受到2019冠状病毒病的严重影响。目前还没有特定的小分子抑制剂来对抗这种可怕的病毒。许多抗病毒药物、抗疟疾药、抗寄生虫药、抗菌药、免疫抑制抗炎药和免疫刺激药已被重新用于治疗COVID-19。但这些药物对COVID-19靶点的确切作用机制尚未实验。在化疗药物的作用下，病毒可能发生遗传物质变化，产生多种毒株，这是新冠病毒可怕袭击的主要原因。核遗传成分由主要蛋白酶和RNA依赖RNA聚合酶(RdRp)组成，它们负责产生新生病毒粒子和病毒在宿主细胞中的复制。为了探索各种小分子抑制剂的生化机制，可以尝试利用核磁共振晶体学进行基于结构的药物设计。该过程通过在蛋白质表面明确的口袋上结合化学配体来识别和验证与疾病发病有关的目标蛋白。这样就可以预测靶腔内配体的结合模式，从而设计有效的SARS-CoV-2抑制剂。

关键词: covid -19, SARS-CoV-2，主蛋白酶，RNA依赖RNA聚合酶(RdRp)，共结晶配体，结合模式，基于结构的晶体学

« Previous Next »
图形摘要

[1]
Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270-3.
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[2]
Yang H, Bartlam M, Rao Z. Drug design targeting the main protease, the Achilles’ heel of coronaviruses. Curr Pharm Des 2006; 12(35): 4573-90.
[http://dx.doi.org/10.2174/138161206779010369] [PMID: 17168763]
[3]
Belouzard S, Millet JK, Licitra BN, Whittaker GR. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses 2012; 4(6): 1011-33.
[http://dx.doi.org/10.3390/v4061011] [PMID: 22816037]
[4]
Hilgenfeld R. From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design. FEBS J 2014; 281(18): 4085-96.
[http://dx.doi.org/10.1111/febs.12936] [PMID: 25039866]
[5]
Chang CK, Lo SC, Wang YS, Hou MH. Recent insights into the development of therapeutics against coronavirus diseases by targeting N protein. Drug Discov Today 2016; 21(4): 562-72.
[http://dx.doi.org/10.1016/j.drudis.2015.11.015] [PMID: 26691874]
[6]
Paules CI, Marston HD, Fauci AS. Coronavirus infections-More than just the common cold. JAMA 2020; 323(8): 707-8.
[http://dx.doi.org/10.1001/jama.2020.0757] [PMID: 31971553]
[7]
Saif LJ. Animal coronaviruses: what can they teach us about the severe acute respiratory syndrome? Rev Sci Tech 2004; 23(2): 643-60.
[http://dx.doi.org/10.20506/rst.23.2.1513] [PMID: 15702725]
[8]
Al-Osail AM, Al-Wazzah MJ. The history and epidemiology of Middle East respiratory syndrome corona virus. Multidiscip Respir Med 2017; 12(20): 20.
[http://dx.doi.org/10.1186/s40248-017-0101-8] [PMID: 28794876]
[9]
J Alsaadi EA. Jones IM. Membrane binding proteins of coronaviruses. Future Virol 2019; 14(4): 275-86.
[http://dx.doi.org/10.2217/fvl-2018-0144] [PMID: 32201500]
[10]
Schoeman D, Fielding BC. Coronavirus envelope protein: current knowledge. Virol J 2019; 16(1): 69.
[http://dx.doi.org/10.1186/s12985-019-1182-0] [PMID: 31133031]
[11]
Verheije MH, Hagemeijer MC, Ulasli M, et al. The coronavirus nucleocapsid protein is dynamically associated with the replication-transcription complexes. J Virol 2010; 84(21): 11575-9.
[http://dx.doi.org/10.1128/JVI.00569-10] [PMID: 20739524]
[12]
McBride R, van Zyl M, Fielding BC. The coronavirus nucleocapsid is a multifunctional protein. Viruses 2014; 6(8): 2991-3018.
[http://dx.doi.org/10.3390/v6082991] [PMID: 25105276]
[13]
Guo Y, Korteweg C, McNutt MA, Gu J. Pathogenetic mechanisms of severe acute respiratory syndrome. Virus Res 2008; 133(1): 4-12.
[http://dx.doi.org/10.1016/j.virusres.2007.01.022] [PMID: 17825937]
[14]
Sutton G, Fry E, Carter L, et al. The nsp9 replicase protein of SARS-coronavirus, structure and functional insights. Structure 2004; 12(2): 341-53.
[http://dx.doi.org/10.1016/j.str.2004.01.016] [PMID: 14962394]
[15]
Jiang Y, Yin W, Xu HE. RNA-dependent RNA polymerase: Structure, mechanism, and drug discovery for COVID-19. Biochem Biophys Res Commun 2021; 538: 47-53.
[http://dx.doi.org/10.1016/j.bbrc.2020.08.116] [PMID: 32943188]
[16]
Risco C, Rodríguez JR, López-Iglesias C, Carrascosa JL, Esteban M, Rodríguez D. Endoplasmic reticulum-Golgi intermediate compartment membranes and vimentin filaments participate in vaccinia virus assembly. J Virol 2002; 76(4): 1839-55.
[http://dx.doi.org/10.1128/JVI.76.4.1839-1855.2002] [PMID: 11799179]
[17]
Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol 2020; 92(4): 418-23.
[http://dx.doi.org/10.1002/jmv.25681] [PMID: 31967327]
[18]
Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol 2015; 1282: 1-23.
[http://dx.doi.org/10.1007/978-1-4939-2438-7_1] [PMID: 25720466]
[19]
V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol 2021; 19(3): 155-70.
[http://dx.doi.org/10.1038/s41579-020-00468-6] [PMID: 33116300]
[20]
Lindner HA, Fotouhi-Ardakani N, Lytvyn V, Lachance P, Sulea T, Ménard R. The papain-like protease from the severe acute respiratory syndrome coronavirus is a deubiquitinating enzyme. J Virol 2005; 79(24): 15199-208.
[http://dx.doi.org/10.1128/JVI.79.24.15199-15208.2005] [PMID: 16306591]
[21]
Jo S, Kim S, Shin DH, Kim MS. Inhibition of SARS-CoV 3CL protease by flavonoids. J Enzyme Inhib Med Chem 2020; 35(1): 145-51.
[http://dx.doi.org/10.1080/14756366.2019.1690480] [PMID: 31724441]
[22]
Froggatt HM, Heaton BE, Heaton NS. Development of a fluorescence-based, high-throughput SARS-CoV-2 3CLpro reporter assay. J Virol 2020; 94(22): e01265-20.
[http://dx.doi.org/10.1128/JVI.01265-20] [PMID: 32843534]
[23]
Zhang L, Lin D, Sun X, et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science 2020; 368(6489): 409-12.
[http://dx.doi.org/10.1126/science.abb3405] [PMID: 32198291]
[24]
Hu T, Zhang Y, Li L, et al. Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different con-formational changes in crystal structure. Virology 2009; 388(2): 324-34.
[http://dx.doi.org/10.1016/j.virol.2009.03.034] [PMID: 19409595]
[25]
Hsu MF, Kuo CJ, Chang KT, et al. Mechanism of the maturation process of SARS-CoV 3CL protease. J Biol Chem 2005; 280(35): 31257-66.
[http://dx.doi.org/10.1074/jbc.M502577200] [PMID: 15788388]
[26]
Barretto N, Jukneliene D, Ratia K, Chen Z, Mesecar AD, Baker SC. The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity. J Virol 2005; 79(24): 15189-98.
[http://dx.doi.org/10.1128/JVI.79.24.15189-15198.2005] [PMID: 16306590]
[27]
Han YS, Chang GG, Juo CG, et al. Papain-like protease 2 (PLP2) from severe acute respiratory syndrome coronavirus (SARS-CoV): expression, purification, characterization, and inhibition. Biochemistry 2005; 44(30): 10349-59.
[http://dx.doi.org/10.1021/bi0504761] [PMID: 16042412]
[28]
Kirchdoerfer RN, Ward AB. Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat Commun 2019; 10(1): 2342.
[http://dx.doi.org/10.1038/s41467-019-10280-3] [PMID: 31138817]
[29]
Ahn DG, Choi JK, Taylor DR, Oh JW. Biochemical characterization of a recombinant SARS coronavirus nsp12 RNA-dependent RNA polymerase capable of copying viral RNA templates. Arch Virol 2012; 157(11): 2095-104.
[http://dx.doi.org/10.1007/s00705-012-1404-x] [PMID: 22791111]
[30]
Subissi L, Posthuma CC, Collet A, et al. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. Proc Natl Acad Sci USA 2014; 111(37): E3900-9.
[http://dx.doi.org/10.1073/pnas.1323705111] [PMID: 25197083]
[31]
McDonald SM. RNA synthetic mechanisms employed by diverse families of RNA viruses. Wiley Interdiscip Rev RNA 2013; 4(4): 351-67.
[http://dx.doi.org/10.1002/wrna.1164] [PMID: 23606593]
[32]
Gao Y, Yan L, Huang Y, et al. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science 2020; 368(6492): 779-82.
[http://dx.doi.org/10.1126/science.abb7498] [PMID: 32277040]
[33]
Yin W, Mao C, Luan X, et al. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science 2020; 368(6498): 1499-504.
[http://dx.doi.org/10.1126/science.abc1560] [PMID: 32358203]
[34]
Wang Q, Wu J, Wang H, et al. Structural basis for RNA replication by the SARS-CoV-2 polymerase. Cell 2020; 182(2): 417-428.e13.
[http://dx.doi.org/10.1016/j.cell.2020.05.034] [PMID: 32526208]
[35]
Kendrew JC, Bodo G, Dintzis HM, Parrish RG, Wyckoff H, Phillips DC. A three-dimensional model of the myoglobin molecule obtained by x-ray analysis. Nature 1958; 181(4610): 662-6.
[http://dx.doi.org/10.1038/181662a0] [PMID: 13517261]
[36]
Congreve M, Murray CW, Blundell TL. Structural biology and drug discovery. Drug Discov Today 2005; 10(13): 895-907.
[http://dx.doi.org/10.1016/S1359-6446(05)03484-7] [PMID: 15993809]
[37]
Nandi S, Kumar M, Saxena M, Saxena AK. The antiviral and antimalarial drug repurposing in quest of chemotherapeutics to combat covid-19 utilizing structure-based molecular docking. Comb Chem High Throughput Screen 2020.
[http://dx.doi.org/10.2174/1386207323999200824115536] [PMID: 32838713]
[38]
Meyer EF. The first years of the Protein Data Bank. Protein Sci 1997; 6(7): 1591-7.
[http://dx.doi.org/10.1002/pro.5560060724] [PMID: 9232661]
[39]
St John SE, Tomar S, Stauffer SR, Mesecar AD. Targeting zoonotic viruses: Structure-based inhibition of the 3C-like protease from bat coronavirus HKU4-The likely reservoir host to the human coronavirus that causes Middle East Respiratory Syndrome (MERS). Bioorg Med Chem 2015; 23(17): 6036-48.
[http://dx.doi.org/10.1016/j.bmc.2015.06.039] [PMID: 26190463]
[40]
Douangamath A, Fearon D, Gehrtz P, et al. Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease. Nat Commun 2020; 11(1): 5047-7.
[http://dx.doi.org/10.1038/s41467-020-18709-w] [PMID: 33028810]
[41]
Jin Z, Du X, Xu Y, et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 2020; 582(7811): 289-93.
[http://dx.doi.org/10.1038/s41586-020-2223-y] [PMID: 32272481]
[42]
Su HX, Yao S, Zhao WF, et al. Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients. Acta Pharmacol Sin 2020; 41(9): 1167-77.
[http://dx.doi.org/10.1038/s41401-020-0483-6] [PMID: 32737471]
[43]
Availalble from: https://www.rcsb.org/structure/6W63
[44]
Ma C, Sacco MD, Hurst B, et al. Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. bioRxiv 2020.2020.04.20.051581.
[http://dx.doi.org/10.1038/s41422-020-0356-z] [PMID: 32511378]
[45]
Goyal B, Goyal D. Targeting the dimerization of the main protease of coronaviruses: A potential broad-spectrum therapeutic strategy. ACS Comb Sci 2020; 22(6): 297-305.
[http://dx.doi.org/10.1021/acscombsci.0c00058] [PMID: 32402186]
[46]
Jin Z, Zhao Y, Sun Y, et al. Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur. Nat Struct Mol Biol 2020; 27(6): 529-32.
[http://dx.doi.org/10.1038/s41594-020-0440-6] [PMID: 32382072]
[47]
Availalble from: https://www.rcsb.org/structure/7JYC
[48]
Dai W, Zhang B, Jiang XM, et al. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science 2020; 368(6497): 1331-5.
[http://dx.doi.org/10.1126/science.abb4489] [PMID: 32321856]
[49]
Prongay AJ, Guo Z, Yao N, et al. Discovery of the HCV NS3/4A protease inhibitor (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (Sch 503034) II. Key steps in structure-based op-timization. J Med Chem 2007; 50(10): 2310-8.
[http://dx.doi.org/10.1021/jm060173k] [PMID: 17444623]
[50]
Kim Y, Lovell S, Tiew KC, et al. Broad-spectrum antivirals against 3C or 3C-like proteases of picornaviruses, noroviruses, and corona-viruses. J Virol 2012; 86(21): 11754-62.
[http://dx.doi.org/10.1128/JVI.01348-12] [PMID: 22915796]
[51]
Yang H, Xie W, Xue X, et al. Design of wide-spectrum inhibitors targeting coronavirus main proteases. PLoS Biol 2005; 3(10): e324.
[http://dx.doi.org/10.1371/journal.pbio.0030324] [PMID: 16128623]
[52]
Zhang L, Zhou R. Structural basis of the potential binding mechanism of remdesivir to SARS-CoV-2 RNA-dependent RNA polymerase. J Phys Chem B 2020; 124(32): 6955-62.
[http://dx.doi.org/10.1021/acs.jpcb.0c04198] [PMID: 32521159]
[53]
Nandi S, Roy H, Gummadi A, Saxena A. Exploring spike protein as potential target of novel coronavirus and to inhibit the viability uti-lizing natural agents. Curr Drug Targets 2021; 22: 1-15.
[http://dx.doi.org/10.2174/1389450122666210309105820] [PMID: 33687893]
[54]
Badshah SL, Riaz A, Muhammad A, et al. Isolation, characterization, and medicinal potential of polysaccharides of Morchella esculenta. Molecules 2021; 26(5): 1-12.
[http://dx.doi.org/10.3390/molecules26051459] [PMID: 33800212]
[55]
Ullah A, Munir S, Badshah SL, et al. Important flavonoids and their role as a therapeutic agent. Molecules 2020; 25(22): 5243.
[http://dx.doi.org/10.3390/molecules25225243] [PMID: 33187049]
[56]
Emwas AH, Szczepski K, Poulson BG, et al. NMR as a “gold standard” method in drug design and discovery. Molecules 2020; 25(20): 4597.
[http://dx.doi.org/10.3390/molecules25204597] [PMID: 33050240]

Rights & Permissions Print Cite
Article Metrics
39
1
World Malaria Day
© 2024 Bentham Science Publishers | Privacy Policy