Abstract
Introduction: The world is currently facing a pandemic initiated by the new coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus. Viral transcription and replication are the fundamental processes of any virus. They allow the synthesis of genetic material and the consequent multiplication of the virus to infect other cells or organisms.
Methods: The most important protein in SARS-CoV-2 is the RNA polymerase (RdRp or nsp12), responsible for both processes. The structure of this protein (PDB ID: 6M71) was used as a target in the application of computational strategies for a drug search, like virtual screening and molecular docking. Here, the Pathogen Box database of chemical compounds was used together with Remdesivir, Beclabuvir, and Sofosbuvir drugs as potential inhibitors of nsp12.
Results: The results showed Top10 potential target inhibitors with binding energy (ΔG) higher than those of the positive controls, of which TCMDC-134153 and TCMDC-135052, both with ΔG = −7.53 kcal/mol, present interactions with three important residues of the nsp12 catalytic site.
Conclusion: These proposed ligands would be used for subsequent validation by molecular dynamics, where they can be considered as drugs for the development of effective treatments against this new pandemic.
Keywords: SARS-CoV-2, nsp12, RNA polymerase, molecular docking, drug repurposing
[1]
Woolhouse, J. RNA Viruses: A Case Study of the Biology of Emerging Infectious Diseases. Microbiol. Spectr., 2013, 1(1)
[http://dx.doi.org/10.1128/microbiolspec.OH-0001-2012]
[http://dx.doi.org/10.1128/microbiolspec.OH-0001-2012]
[2]
Carrasco-Hernandez, R.; Jácome, R.; López Vidal, Y.; Ponce de León, S. Are RNA Viruses Candidate Agents for the Next Global Pandemic? A Review. ILAR J., 2017, 58(3), 343-358.
[http://dx.doi.org/10.1093/ilar/ilx026] [PMID: 28985316]
[http://dx.doi.org/10.1093/ilar/ilx026] [PMID: 28985316]
[4]
Fehr, A.R.; Perlman, S. Coronaviruses: An Overview of Their Replication and Pathogenesis. In: Coronaviruses; Methods in Molecular Biology;; Maier, H. J.; Bickerton, E.; Britton, P., Eds.; Springer New York:: New York, NY, 2015; 1282, pp. 1-23.
[http://dx.doi.org/10.1007/978-1-4939-2438-7_1]
[http://dx.doi.org/10.1007/978-1-4939-2438-7_1]
[5]
Cheng, V.C.C.; Lau, S.K.P.; Woo, P.C.Y.; Yuen, K.Y. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin. Microbiol. Rev., 2007, 20(4), 660-694.
[http://dx.doi.org/10.1128/CMR.00023-07] [PMID: 17934078]
[http://dx.doi.org/10.1128/CMR.00023-07] [PMID: 17934078]
[6]
Chan, J.F.W.; Lau, S.K.P.; To, K.K.W.; Cheng, V.C.C.; Woo, P.C.Y.; Yuen, K-Y. Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clin. Microbiol. Rev., 2015, 28(2), 465-522.
[http://dx.doi.org/10.1128/CMR.00102-14] [PMID: 25810418]
[http://dx.doi.org/10.1128/CMR.00102-14] [PMID: 25810418]
[7]
Dong, E.; Du, H.; Gardner, L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect. Dis., 2020, 20(5), 533-534.
[http://dx.doi.org/10.1016/S1473-3099(20)30120-1] [PMID: 32087114]
[http://dx.doi.org/10.1016/S1473-3099(20)30120-1] [PMID: 32087114]
[8]
Yu, S.; Chen, K.; Fang, L.; Mao, H.; Lou, X.; Li, C.; Zhang, Y. Comparison and Analysis of Neutralizing Antibody Levels in Serum after Inoculating with SARS-CoV-2, MERS-CoV, or SARS-CoV Vaccines in Humans. Vaccines (Basel), 2021, 9(6), 588.
[http://dx.doi.org/10.3390/vaccines9060588] [PMID: 34199384]
[http://dx.doi.org/10.3390/vaccines9060588] [PMID: 34199384]
[9]
Amanat, F.; Krammer, F. SARS-CoV-2 Vaccines: Status Report. Immunity, 2020, 52(4), 583-589.
[http://dx.doi.org/10.1016/j.immuni.2020.03.007] [PMID: 32259480]
[http://dx.doi.org/10.1016/j.immuni.2020.03.007] [PMID: 32259480]
[10]
Singh, J.; Samal, J.; Kumar, V.; Sharma, J.; Agrawal, U.; Ehtesham, N.Z.; Sundar, D.; Rahman, S.A.; Hira, S.; Hasnain, S.E. Structure-Function Analyses of New SARS-CoV-2 Variants B.1.1.7, B.1.351 and B.1.1.28.1: Clinical, Diagnostic, Therapeutic and Public Health Implications. Viruses, 2021, 13(3), 439.
[http://dx.doi.org/10.3390/v13030439] [PMID: 33803400]
[http://dx.doi.org/10.3390/v13030439] [PMID: 33803400]
[11]
Plante, J.A.; Liu, Y.; Liu, J.; Xia, H.; Johnson, B.A.; Lokugamage, K.G.; Zhang, X.; Muruato, A.E.; Zou, J.; Fontes-Garfias, C.R.; Mirchandani, D.; Scharton, D.; Bilello, J.P.; Ku, Z.; An, Z.; Kalveram, B.; Freiberg, A.N.; Menachery, V.D.; Xie, X.; Plante, K.S.; Weaver, S.C.; Shi, P-Y. Spike mutation D614G alters SARS-CoV-2 fitness. Nature, 2021, 592(7852), 116-121.
[http://dx.doi.org/10.1038/s41586-020-2895-3] [PMID: 33106671]
[http://dx.doi.org/10.1038/s41586-020-2895-3] [PMID: 33106671]
[12]
Cheng, H.; Peng, Z.; Luo, W.; Si, S.; Mo, M.; Zhou, H.; Xin, X.; Liu, H.; Yu, Y. Efficacy and Safety of COVID-19 Vaccines in Phase III Trials: A Meta-Analysis. Vaccines (Basel), 2021, 9(6), 582.
[http://dx.doi.org/10.3390/vaccines9060582] [PMID: 34206032]
[http://dx.doi.org/10.3390/vaccines9060582] [PMID: 34206032]
[13]
White, K.A.; Enjuanes, L.; Berkhout, B. RNA virus replication, transcription and recombination. RNA Biol., 2011, 8(2), 182-183.
[http://dx.doi.org/10.4161/rna.8.2.15663] [PMID: 21593586]
[http://dx.doi.org/10.4161/rna.8.2.15663] [PMID: 21593586]
[14]
Gao, Y.; Yan, L.; Huang, Y.; Liu, F.; Zhao, Y.; Cao, L.; Wang, T.; Sun, Q.; Ming, Z.; Zhang, L.; Ge, J.; Zheng, L.; Zhang, Y.; Wang, H.; Zhu, Y.; Zhu, C.; Hu, T.; Hua, T.; Zhang, B.; Yang, X.; Li, J.; Yang, H.; Liu, Z.; Xu, W.; Guddat, L.W.; Wang, Q.; Lou, Z.; Rao, Z. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science, 2020, 368(6492), 779-782.
[http://dx.doi.org/10.1126/science.abb7498] [PMID: 32277040]
[http://dx.doi.org/10.1126/science.abb7498] [PMID: 32277040]
[15]
Molecular Biology of the SARSCoronavirus; Lal, S. K; Heidelberg, S.B., Ed.; Berlin, Heidelberg, 2010.
[http://dx.doi.org/10.1007/978-3-642-03683-5]
[http://dx.doi.org/10.1007/978-3-642-03683-5]
[16]
Zhang, W-F.; Stephen, P.; Thériault, J-F.; Wang, R.; Lin, S-X. Novel Coronavirus Polymerase and Nucleotidyl-Transferase Structures: Potential to Target New Outbreaks. J. Phys. Chem. Lett., 2020, 11(11), 4430-4435.
[http://dx.doi.org/10.1021/acs.jpclett.0c00571] [PMID: 32392072]
[http://dx.doi.org/10.1021/acs.jpclett.0c00571] [PMID: 32392072]
[17]
Venkataraman, S.; Prasad, B.V.L.S.; Selvarajan, R. RNA Dependent RNA Polymerases: Insights from Structure, Function and Evolution. Viruses, 2018, 10(2), 76.
[http://dx.doi.org/10.3390/v10020076] [PMID: 29439438]
[http://dx.doi.org/10.3390/v10020076] [PMID: 29439438]
[18]
Elfiky, A.A. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci., 2020, 248, 117477.
[http://dx.doi.org/10.1016/j.lfs.2020.117477] [PMID: 32119961]
[http://dx.doi.org/10.1016/j.lfs.2020.117477] [PMID: 32119961]
[19]
te Velthuis, A.J.W. Common and unique features of viral RNA-dependent polymerases. Cell. Mol. Life Sci., 2014, 71(22), 4403-4420.
[http://dx.doi.org/10.1007/s00018-014-1695-z] [PMID: 25080879]
[http://dx.doi.org/10.1007/s00018-014-1695-z] [PMID: 25080879]
[20]
Garriga, D.; Ferrer-Orta, C.; Querol-Audí, J.; Oliva, B.; Verdaguer, N. Role of motif B loop in allosteric regulation of RNA-dependent RNA polymerization activity. J. Mol. Biol., 2013, 425(13), 2279-2287.
[http://dx.doi.org/10.1016/j.jmb.2013.03.034] [PMID: 23542342]
[http://dx.doi.org/10.1016/j.jmb.2013.03.034] [PMID: 23542342]
[21]
Kirchdoerfer, R.N.; Ward, A.B. 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]
[http://dx.doi.org/10.1038/s41467-019-10280-3] [PMID: 31138817]
[22]
Subissi, L.; Posthuma, C.C.; Collet, A.; Zevenhoven-Dobbe, J.C.; Gorbalenya, A.E.; Decroly, E.; Snijder, E.J.; Canard, B.; Imbert, I. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. Proc. Natl. Acad. Sci. USA, 2014, 111(37), E3900-E3909.
[http://dx.doi.org/10.1073/pnas.1323705111] [PMID: 25197083]
[http://dx.doi.org/10.1073/pnas.1323705111] [PMID: 25197083]
[23]
Wang, Q.; Wu, J.; Wang, H.; Gao, Y.; Liu, Q.; Mu, A.; Ji, W.; Yan, L.; Zhu, Y.; Zhu, C.; Fang, X.; Yang, X.; Huang, Y.; Gao, H.; Liu, F.; Ge, J.; Sun, Q.; Yang, X.; Xu, W.; Liu, Z.; Yang, H.; Lou, Z.; Jiang, B.; Guddat, L.W.; Gong, P.; Rao, Z. 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]
[http://dx.doi.org/10.1016/j.cell.2020.05.034] [PMID: 32526208]
[24]
Yin, W.; Mao, C.; Luan, X.; Shen, D-D.; Shen, Q.; Su, H.; Wang, X.; Zhou, F.; Zhao, W.; Gao, M.; Chang, S.; Xie, Y-C.; Tian, G.; Jiang, H-W.; Tao, S-C.; Shen, J.; Jiang, Y.; Jiang, H.; Xu, Y.; Zhang, S.; Zhang, Y.; Xu, H.E. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science, 2020, 368(6498), 1499-1504.
[http://dx.doi.org/10.1126/science.abc1560] [PMID: 32358203]
[http://dx.doi.org/10.1126/science.abc1560] [PMID: 32358203]
[25]
Imbert, I.; Guillemot, J-C.; Bourhis, J-M.; Bussetta, C.; Coutard, B.; Egloff, M-P.; Ferron, F.; Gorbalenya, A.E.; Canard, B. A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus. EMBO J., 2006, 25(20), 4933-4942.
[http://dx.doi.org/10.1038/sj.emboj.7601368] [PMID: 17024178]
[http://dx.doi.org/10.1038/sj.emboj.7601368] [PMID: 17024178]
[26]
Zhai, Y.; Sun, F.; Li, X.; Pang, H.; Xu, X.; Bartlam, M.; Rao, Z. Insights into SARS-CoV transcription and replication from the structure of the nsp7-nsp8 hexadecamer. Nat. Struct. Mol. Biol., 2005, 12(11), 980-986.
[http://dx.doi.org/10.1038/nsmb999] [PMID: 16228002]
[http://dx.doi.org/10.1038/nsmb999] [PMID: 16228002]
[27]
Ahn, D-G.; Choi, J-K.; Taylor, D.R.; Oh, J-W. Biochemical characterization of a recombinant SARS coronavirus nsp12 RNA-dependent RNA polymerase capable of copying viral RNA templates. Arch. Virol., 2012, 157(11), 2095-2104.
[http://dx.doi.org/10.1007/s00705-012-1404-x] [PMID: 22791111]
[http://dx.doi.org/10.1007/s00705-012-1404-x] [PMID: 22791111]
[28]
Peng, Q.; Peng, R.; Yuan, B.; Zhao, J.; Wang, M.; Wang, X.; Wang, Q.; Sun, Y.; Fan, Z.; Qi, J.; Gao, G.F.; Shi, Y. Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2. Cell Rep., 2020, 31(11), 107774.
[http://dx.doi.org/10.1016/j.celrep.2020.107774] [PMID: 32531208]
[http://dx.doi.org/10.1016/j.celrep.2020.107774] [PMID: 32531208]
[29]
Van Voorhis, W.C.; Adams, J.H.; Adelfio, R.; Ahyong, V.; Akabas, M.H.; Alano, P.; Alday, A.; Alemán Resto, Y.; Alsibaee, A.; Alzualde, A.; Andrews, K.T.; Avery, S.V.; Avery, V.M.; Ayong, L.; Baker, M.; Baker, S.; Ben Mamoun, C.; Bhatia, S.; Bickle, Q.; Bounaadja, L.; Bowling, T.; Bosch, J.; Boucher, L.E.; Boyom, F.F.; Brea, J.; Brennan, M.; Burton, A.; Caffrey, C.R.; Camarda, G.; Carrasquilla, M.; Carter, D.; Belen Cassera, M.; Chih-Chien Cheng, K.; Chindaudomsate, W.; Chubb, A.; Colon, B.L.; Colón-López, D.D.; Corbett, Y.; Crowther, G.J.; Cowan, N.; D’Alessandro, S.; Le Dang, N.; Delves, M.; DeRisi, J.L.; Du, A.Y.; Duffy, S.; Abd El-Salam El-Sayed, S.; Ferdig, M.T.; Fernández Robledo, J.A.; Fidock, D.A.; Florent, I.; Fokou, P.V.T.; Galstian, A.; Gamo, F.J.; Gokool, S.; Gold, B.; Golub, T.; Goldgof, G.M.; Guha, R.; Guiguemde, W.A.; Gural, N.; Guy, R.K.; Hansen, M.A.E.; Hanson, K.K.; Hemphill, A.; Hooft van Huijsduijnen, R.; Ho-rii, T.; Horrocks, P.; Hughes, T.B.; Huston, C.; Igarashi, I.; Ingram-Sieber, K.; Itoe, M.A.; Jadhav, A. Naranuntarat Jensen, A.; Jensen, L.T.; Jiang, R.H.Y.; Kaiser, A.; Keiser, J.; Ketas, T.; Kicka, S.; Kim, S.; Kirk, K.; Kumar, V.P.; Kyle, D.E.; Lafuente, M.J.; Landfear, S.; Lee, N.; Lee, S.; Lehane, A.M.; Li, F.; Little, D.; Liu, L.; Llinás, M.; Loza, M.I.; Lubar, A.; Lucantoni, L.; Lucet, I.; Maes, L.; Mancama, D.; Mansour, N.R.; March, S.; McGowan, S.; Medina Vera, I.; Meister, S.; Mercer, L.; Mestres, J.; Mfopa, A.N.; Misra, R.N.; Moon, S.; Moore, J.P.; Morais Rodrigues da Costa, F.; Müller, J.; Muriana, A.; Nakazawa Hewitt, S.; Nare, B.; Nathan, C.; Narraidoo, N.; Nawaratna, S.; Ojo, K.K.; Ortiz, D.; Panic, G.; Papadatos, G.; Parapini, S.; Patra, K.; Pham, N.; Prats, S.; Plouffe, D.M.; Poulsen, S-A.; Pradhan, A.; Quevedo, C.; Quinn, R.J.; Rice, C.A.; Abdo Rizk, M.; Ruecker, A.; St Onge, R.; Salgado Ferreira, R.; Samra, J.; Robinett, N.G.; Schlecht, U.; Schmitt, M.; Silva Villela, F.; Silvestrini, F.; Sinden, R.; Smith, D.A.; Soldati, T.; Spitzmüller, A.; Stamm, S.M.; Sullivan, D.J.; Sullivan, W.; Suresh, S.; Suzuki, B.M.; Suzuki, Y.; Swamidass, S.J.; Taramelli, D.; Tchokouaha, L.R.Y.; Theron, A.; Thomas, D.; Tonissen, K.F.; Townson, S.; Tripathi, A.K.; Trofimov, V.; Udenze, K.O.; Ullah, I.; Vallieres, C.; Vigil, E.; Vinetz, J.M.; Voong Vinh, P.; Vu, H.; Watanabe, N.A.; Weatherby, K.; White, P.M.; Wilks, A.F.; Winzeler, E.A.; Wojcik, E.; Wree, M.; Wu, W.; Yokoyama, N.; Zollo, P.H.A.; Abla, N.; Blasco, B.; Burrows, J.; Laleu, B.; Leroy, D.; Spangenberg, T.; Wells, T.; Willis, P.A. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond. PLoS Pathog., 2016, 12(7), e1005763.
[http://dx.doi.org/10.1371/journal.ppat.1005763] [PMID: 27467575]
[http://dx.doi.org/10.1371/journal.ppat.1005763] [PMID: 27467575]
[30]
Duffy, S.; Sykes, M.L.; Jones, A.J.; Shelper, T.B.; Simpson, M.; Lang, R.; Poulsen, S-A.; Sleebs, B.E.; Avery, V.M. Screening the Medicines for Malaria Venture Pathogen Box across Multiple Pathogens Reclassifies Starting Points for Open-Source Drug Discovery. Antimicrob. Agents Chemother., 2017, 61(9), e00379-e17.
[http://dx.doi.org/10.1128/AAC.00379-17] [PMID: 28674055]
[http://dx.doi.org/10.1128/AAC.00379-17] [PMID: 28674055]
[31]
Spalenka, J.; Escotte-Binet, S.; Bakiri, A.; Hubert, J.; Renault, J-H.; Velard, F.; Duchateau, S.; Aubert, D.; Huguenin, A.; Villena, I. Discovery of New Inhibitors of Toxoplasma gondii via the Pathogen Box. Antimicrob. Agents Chemother., 2018, 62(2), e01640-e17.
[http://dx.doi.org/10.1128/AAC.01640-17] [PMID: 29133550]
[http://dx.doi.org/10.1128/AAC.01640-17] [PMID: 29133550]
[32]
Veale, C.G.L. Unpacking the Pathogen Box-An Open Source Tool for Fighting Neglected Tropical Disease. ChemMedChem, 2019, 14(4), 386-453.
[http://dx.doi.org/10.1002/cmdc.201800755] [PMID: 30614200]
[http://dx.doi.org/10.1002/cmdc.201800755] [PMID: 30614200]
[33]
Hennessey, K.M.; Rogiers, I.C.; Shih, H-W.; Hulverson, M.A.; Choi, R.; McCloskey, M.C.; Whitman, G.R.; Barrett, L.K.; Merritt, E.A.; Paredez, A.R.; Ojo, K.K. Screening of the Pathogen Box for inhibitors with dual efficacy against Giardia lamblia and Cryptosporidium parvum. PLoS Negl. Trop. Dis., 2018, 12(8), e0006673.
[http://dx.doi.org/10.1371/journal.pntd.0006673] [PMID: 30080847]
[http://dx.doi.org/10.1371/journal.pntd.0006673] [PMID: 30080847]
[34]
Vila, T.; Lopez-Ribot, J.L. Screening the Pathogen Box for Identification of Candida albicans Biofilm Inhibitors. Antimicrob. Agents Chemother., 2016, 61(1), e02006-e02016.
[http://dx.doi.org/10.1128/AAC.02006-16] [PMID: 27795383]
[http://dx.doi.org/10.1128/AAC.02006-16] [PMID: 27795383]
[35]
Hodos, R.A.; Kidd, B.A.; Shameer, K.; Readhead, B.P.; Dudley, J.T. In silico methods for drug repurposing and pharmacology. Wiley Interdiscip. Rev. Syst. Biol. Med., 2016, 8(3), 186-210.
[http://dx.doi.org/10.1002/wsbm.1337] [PMID: 27080087]
[http://dx.doi.org/10.1002/wsbm.1337] [PMID: 27080087]
[36]
Park, K. A review of computational drug repurposing. Transl. Clin. Pharmacol., 2019, 27(2), 59-63.
[http://dx.doi.org/10.12793/tcp.2019.27.2.59] [PMID: 32055582]
[http://dx.doi.org/10.12793/tcp.2019.27.2.59] [PMID: 32055582]
[37]
García-Serradilla, M.; Risco, C.; Pacheco, B. Drug repurposing for new, efficient, broad spectrum antivirals. Virus Res., 2019, 264, 22-31.
[http://dx.doi.org/10.1016/j.virusres.2019.02.011] [PMID: 30794895]
[http://dx.doi.org/10.1016/j.virusres.2019.02.011] [PMID: 30794895]
[38]
Pandey, A.; Nikam, A.N.; Shreya, A.B.; Mutalik, S.P.; Gopalan, D.; Kulkarni, S.; Padya, B.S.; Fernandes, G.; Mutalik, S.; Prassl, R. Potential therapeutic targets for combating SARS-CoV-2: Drug repurposing, clinical trials and recent advancements. Life Sci., 2020, 256, 117883.
[http://dx.doi.org/10.1016/j.lfs.2020.117883] [PMID: 32497632]
[http://dx.doi.org/10.1016/j.lfs.2020.117883] [PMID: 32497632]
[39]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[40]
O’Boyle, N.M.; Banck, M.; James, C.A.; Morley, C.; Vander-meersch, T.; Hutchison, G.R. Open Babel: An open chemical toolbox. J. Cheminform., 2011, 3(1), 33.
[http://dx.doi.org/10.1186/1758-2946-3-33] [PMID: 21982300]
[http://dx.doi.org/10.1186/1758-2946-3-33] [PMID: 21982300]
[41]
Ropón-Palacios, G.; Chenet-Zuta, M.E.; Olivos-Ramirez, G.E.; Otazu, K.; Acurio-Saavedra, J.; Camps, I. Potential novel inhibitors against emerging zoonotic pathogen Nipah virus: a virtual screening and molecular dynamics approach. J. Biomol. Struct. Dyn., 2020, 38(11), 3225-3234.
[http://dx.doi.org/10.1080/07391102.2019.1655480] [PMID: 31411538]
[http://dx.doi.org/10.1080/07391102.2019.1655480] [PMID: 31411538]
[42]
Halgren, T.A. Merck Molecular Force Field. I. Basis, Form, Scope, Parameterization, and Performance of MMFF94. J. Comput. Chem., 1996, 17(5–6), 490-519.
[http://dx.doi.org/10.1002/(SICI)1096-987X(199604)17:5/6<490:AID-JCC1>3.0.CO;2-P]
[http://dx.doi.org/10.1002/(SICI)1096-987X(199604)17:5/6<490:AID-JCC1>3.0.CO;2-P]
[43]
Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The Protein Data Bank. Nucleic Acids Res., 2000, 28(1), 235-242.
[http://dx.doi.org/10.1093/nar/28.1.235] [PMID: 10592235]
[http://dx.doi.org/10.1093/nar/28.1.235] [PMID: 10592235]
[44]
Jo, S.; Kim, T.; Iyer, V.G. Im, W. CHARMM-GUI: A web-based graphical user interface for CHARMM. J. Comput. Chem., 2008, 29(11), 1859-1865.
[http://dx.doi.org/10.1002/jcc.20945] [PMID: 18351591]
[http://dx.doi.org/10.1002/jcc.20945] [PMID: 18351591]
[45]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDock-Tools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[46]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading. J. Comput. Chem., 2009.
[http://dx.doi.org/10.1002/jcc.21334]
[http://dx.doi.org/10.1002/jcc.21334]
[47]
Blanco Capurro, J.I.; Di Paola, M.; Gamarra, M.D.; Martí, M.A.; Modenutti, C.P. An efficient use of X-ray information, homology modeling, molecular dynamics and knowledge-based docking techniques to predict protein-monosaccharide complexes. Glycobiology, 2019, 29(2), 124-136.
[http://dx.doi.org/10.1093/glycob/cwy102] [PMID: 30407518]
[http://dx.doi.org/10.1093/glycob/cwy102] [PMID: 30407518]
[48]
Solis, F.J.; Wets, R.J-B. Minimization by Random Search Techniques. Math. Oper. Res., 1981, 6(1), 19-30.
[http://dx.doi.org/10.1287/moor.6.1.19]
[http://dx.doi.org/10.1287/moor.6.1.19]
[49]
DeLano, W. L. Pymol: An Open-Source Molecular Graphics Tool, Software. CCP4 Newsletter on protein crystallography., 2002.
[50]
Baker, N.A.; Sept, D.; Joseph, S.; Holst, M.J.; McCammon, J.A. Electrostatics of nanosystems: application to microtubules and the ribosome. Proc. Natl. Acad. Sci. USA, 2001, 98(18), 10037-10041.
[http://dx.doi.org/10.1073/pnas.181342398] [PMID: 11517324]
[http://dx.doi.org/10.1073/pnas.181342398] [PMID: 11517324]
[51]
Salentin, S.; Schreiber, S.; Haupt, V.J.; Adasme, M.F.; Schroeder, M. PLIP: fully automated protein-ligand interaction profiler. Nucleic Acids Res., 2015, 43(W1), W443-7.
[http://dx.doi.org/10.1093/nar/gkv315] [PMID: 25873628]
[http://dx.doi.org/10.1093/nar/gkv315] [PMID: 25873628]
[52]
Jones, D.S. History in a Crisis - Lessons for Covid-19. N. Engl. J. Med., 2020, 382(18), 1681-1683.
[http://dx.doi.org/10.1056/NEJMp2004361] [PMID: 32163699]
[http://dx.doi.org/10.1056/NEJMp2004361] [PMID: 32163699]
[53]
Wu, C.; Liu, Y.; Yang, Y.; Zhang, P.; Zhong, W.; Wang, Y.; Wang, Q.; Xu, Y.; Li, M.; Li, X.; Zheng, M.; Chen, L.; Li, H. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm. Sin. B, 2020, 10(5), 766-788.
[http://dx.doi.org/10.1016/j.apsb.2020.02.008] [PMID: 32292689]
[http://dx.doi.org/10.1016/j.apsb.2020.02.008] [PMID: 32292689]
[54]
Ziebuhr, J. Molecular biology of severe acute respiratory syndrome coronavirus. Curr. Opin. Microbiol., 2004, 7(4), 412-419.
[http://dx.doi.org/10.1016/j.mib.2004.06.007] [PMID: 15358261]
[http://dx.doi.org/10.1016/j.mib.2004.06.007] [PMID: 15358261]
[55]
Posthuma, C.C.; Te Velthuis, A.J.W.; Snijder, E.J. Nidovirus RNA polymerases: Complex enzymes handling exceptional RNA genomes. Virus Res., 2017, 234, 58-73.
[http://dx.doi.org/10.1016/j.virusres.2017.01.023] [PMID: 28174054]
[http://dx.doi.org/10.1016/j.virusres.2017.01.023] [PMID: 28174054]
[56]
Jácome, R.; Becerra, A.; Ponce de León, S.; Lazcano, A. Structural Analysis of Monomeric RNA-Dependent Polymerases: Evolutionary and Therapeutic Implications. PLoS One, 2015, 10(9), e0139001.
[http://dx.doi.org/10.1371/journal.pone.0139001] [PMID: 26397100]
[http://dx.doi.org/10.1371/journal.pone.0139001] [PMID: 26397100]
[57]
Gordon, C.J.; Tchesnokov, E.P.; Woolner, E.; Perry, J.K.; Feng, J.Y.; Porter, D.P.; Götte, M. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J. Biol. Chem., 2020, 295(20), 6785-6797.
[http://dx.doi.org/10.1074/jbc.RA120.013679] [PMID: 32284326]
[http://dx.doi.org/10.1074/jbc.RA120.013679] [PMID: 32284326]
[58]
Hillen, H.S.; Kokic, G.; Farnung, L.; Dienemann, C.; Tegunov, D.; Cramer, P. Structure of replicating SARS-CoV-2 polymerase. Nature, 2020, 584(7819), 154-156.
[http://dx.doi.org/10.1038/s41586-020-2368-8] [PMID: 32438371]
[http://dx.doi.org/10.1038/s41586-020-2368-8] [PMID: 32438371]
[59]
He, Z.; Zhang, J.; Shi, X-H.; Hu, L-L.; Kong, X.; Cai, Y-D.; Chou, K-C. Predicting drug-target interaction networks based on functional groups and biological features. PLoS One, 2010, 5(3), e9603.
[http://dx.doi.org/10.1371/journal.pone.0009603] [PMID: 20300175]
[http://dx.doi.org/10.1371/journal.pone.0009603] [PMID: 20300175]
Article Metrics
5