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Prediction of potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2 using comprehensive drug repurposing and molecular docking approach

Parvez et al., International Journal of Biological Macromolecules, doi:10.1016/j.ijbiomac.2020.09.098
Nov 2020  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now known with p < 0.00000000001 from 102 studies, recognized in 22 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments. c19ivm.org
In Silico study showing that ivermectin, rifabutin, rifapentine, fidaxomicin, and 7-methyl-guanosine-5′-triphosphate-5′-guanosine could be potential inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Authors used molecular docking to screen 44 RNA polymerase inhibitor drug candidates, finding that these five compounds had the highest binding affinity to RdRp, even higher than remdesivir and favipiravir which were used as positive controls. The amino acids Y32, K47, Y122, Y129, H133, N138, D140, T141, S709 and N781 in RdRp were identified as a potential common drug surface hotspot for interaction with the inhibitors.
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Jitobaom, Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Jitobaom, Yang, West Nile Yang, Yellow Fever Mastrangelo, Varghese, Japanese encephalitis Mastrangelo, Chikungunya Varghese, Semliki Forest virus Varghese, Human papillomavirus Li, Epstein-Barr Li, BK Polyomavirus Bennett, and Sindbis virus Varghese.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), inhibits SARS-CoV-2 3CLpro Mody, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing Fauquet, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, Scheim, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 via IMPase inhibition Jitobaom, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, may inhibit SARS-CoV-2 RdRp activity Parvez (B), may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation Liu (C), shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-19 DiNicolantonio, Zhang, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage Zhao, may minimize SARS-CoV-2 induced cardiac damage Liu, Liu (B), increases Bifidobacteria which play a key role in the immune system Hazan, has immunomodulatory Munson and anti-inflammatory DiNicolantonio (B), Yan properties, and has an extensive and very positive safety profile Descotes.
Parvez et al., 30 Nov 2020, peer-reviewed, 8 authors. Contact: sorwersust@yahoo.com, jakir-gen@sust.edu.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Prediction of potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2 using comprehensive drug repurposing and molecular docking approach
Md. Sorwer Alam Parvez, Md. Adnan Karim, Mahmudul Hasan, Jomana Jaman, Ziaul Karim, Tohura Tahsin, Md. Nazmul Hasan, Mohammad Jakir Hosen
International Journal of Biological Macromolecules, doi:10.1016/j.ijbiomac.2020.09.098
The pandemic prevalence of COVID-19 has become a very serious global health issue. Scientists all over the world have been seriously attempting in the discovery of a drug to combat SARS-CoV-2. It has been found that RNAdependent RNA polymerase (RdRp) plays a crucial role in SARS-CoV-2 replication, and thus could be a potential drug target. Here, comprehensive computational approaches including drug repurposing and molecular docking were employed to predict an effective drug candidate targeting RdRp of SARS-CoV-2. This study revealed that Rifabutin, Rifapentine, Fidaxomicin, 7-methyl-guanosine-5′-triphosphate-5′-guanosine and Ivermectin have a potential inhibitory interaction with RdRp of SARS-CoV-2 and could be effective drugs for COVID-19. In addition, virtual screening of the compounds from ZINC database also allowed the prediction of two compounds (ZINC09128258 and ZINC09883305) with pharmacophore features that interact effectively with RdRp of SARS-CoV-2, indicating their potentiality as effective inhibitors of the enzyme. Furthermore, ADME analysis along with analysis of toxicity was also undertaken to check the pharmacokinetics and drug-likeness properties of the two compounds. Comparative structural analysis of protein-inhibitor complexes revealed that the amino acids Y32, K47, Y122, Y129, H133, N138, D140, T141, S709 and N781 are crucial for drug surface hotspot in the RdRp of SARS-CoV-2.
Fig. 10 . PCA results trejectories for the protein-inhibitor complexes. Here, RdRp in complex with (A) Rifabutin, (B) ZINC09128258, and (C) ZINC098833. In this graph, the colour blue to red frames over time. Declaration of competing interest The authors declare that they have no competing interests.
References
Agostini, Andres, Sims, Graham, Sheahan et al., Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease, MBio, doi:10.1128/mBio.00221-18
Agrawal, Singh, Srivastava, Singh, Kishore et al., Benchmarking of Different Molecular Docking Methods for Protein-Peptide Docking
Biovia, Discovery Studio Modeling Environment, Release 2017
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antivir. Res, doi:10.1016/j.antiviral.2020.104787
Case, Cheatham, Darden, Gohlke, Luo et al., The Amber Biomolecular Simulation Programs, doi:10.1002/jcc.20290
Chan, Yuan, Kok, To, Chu et al., A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster, Lancet, doi:10.1016/S0140-6736(20)30154-9
Chen, Zhou, Dong, Qu, Gong et al., Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, Lancet, doi:10.1016/S0140-6736(20)30211-7
Clercq, The design of drugs for HIV and HCV, Nat. Rev. Drug Discov, doi:10.1038/nrd2424
Daina, Michielin, Zoete, SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep, doi:10.1038/srep42717
Daina, Zoete, A BOILED-egg to predict gastrointestinal absorption and brain penetration of small molecules, ChemMedChem, doi:10.1002/cmdc.201600182
Delano, Pymol: an open-source molecular graphics tool, CCP4, Newsl Prot. Crystallogr
Dong, Hu, Gao, Discovering drugs to treat coronavirus disease 2019 (COVID-19), Drug Discov. Ther, doi:10.5582/ddt.2020.01012
Ekins, Mestres, Testa, In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling, Br. J. Pharmacol, doi:10.1038/sj.bjp.0707305
Elfiky, Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): a molecular docking study, Life Sci, doi:10.1016/j.lfs.2020.117592
Fang, Zhang, Xie, Lin, Ying et al., Sensitivity of chest CT for COVID-19: comparison to RT-PCR, Radiology, doi:10.1148/radiol.2020200432
Furuta, Gowen, Takahashi, Shiraki, Smee et al., Favipiravir (T-705), a novel viral RNA polymerase inhibitor, Antivir. Res, doi:10.1016/j.antiviral.2013.09.015
Ganeshpurkar, Gutti, Singh, RNA-dependent RNA polymerases and their emerging roles in antiviral therapy, Viral Polym, doi:10.1016/b978-0-12-815422-9.00001-2
Harrison, Coronavirus puts drug repurposing on the fast track, Nat. Biotechnol, doi:10.1038/d41587-020-00003-1
Hsu, Chen, Lin, Yang, iGEMDOCK: A Graphical Environment of Enhancing GEMDOCK Using Pharmacological Interactions and Post-screening Analysis
Hubbard, Chen, Davis, Informatics and modeling challenges in fragmentbased drug discovery, Curr. Opin. Drug Discov. Dev
Irwin, Shoichet, ZINCa free database of commercially available compounds for virtual screening, J. Chem. Inf. Model, doi:10.1021/ci049714+
Koes, Camacho, ZINCPharmer: pharmacophore search of the ZINC database, Nucleic Acids Res, doi:10.1093/nar/gks378
Lake, What we know so far: COVID-19 current clinical knowledge and research, Clin. Med, doi:10.7861/clinmed.2019-coron
Laskowski, Swindells, LigPlot+: multiple ligand-protein interaction diagrams for drug discovery, J. Chem. Inf. Model, doi:10.1021/ci200227u
Leach, Molecular Modelling: Principles and Applications
Li, Clercq, Therapeutic options for the 2019 novel coronavirus (2019-nCoV), Nat. Rev. Drug Discov, doi:10.1038/d41573-020-00016-0
Li, Du, Wang, Wu, Li et al., In silico estimation of chemical carcinogenicity with binary and ternary classification methods, Mol. Inform, doi:10.1002/minf.201400127
Li, Yu, Zhang, Ren, Peluffo et al., Network Bioinformatics Analysis Provides Insight Into Drug Repurposing for COVID-2019, doi:10.20944/preprints202003.0286.v1
Lung, Lin, Yang, Chou, Shu et al., The potential chemical structure of anti-SARS-CoV-2 RNA-dependent RNA polymerase, J. Med. Virol, doi:10.1002/jmv.25761
Mercorelli, Palù, Loregian, Drug repurposing for viral infectious diseases: how far are we?, Trends Microbiol, doi:10.1016/j.tim.2018.04.004
Mishra, Dahima, In vitro ADME studies of TUG-891, a GPR-120 inhibitor using SWISS ADME predictor, J. Drug Deliv. Ther, doi:10.22270/jddt.v9i2-s.2710
Pal, Berhanu, Desalegn, Kandi, Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2): an update, Cureus, doi:10.7759/cureus.7423
Pizzorno, Padey, Terrier, Rosa-Calatrava, Drug repurposing approaches for the treatment of influenza viral infection: reviving old drugs to fight against a longlived enemy, Front. Immunol, doi:10.3389/fimmu.2019.00531
Polsky, Antiviral chemotherapy for infection with human immunodeficiency virus, Rev. Infect. Dis, doi:10.1093/CLINIDS/11.SUPPLEMENT_7.S1648
Porcheddu, Serra, Kelvin, Kelvin, Rubino, Similarity in case fatality rates (CFR) of COVID-19/SARS-COV-2 in Italy and China, J. Infect. Dev. Count, doi:10.3855/jidc.12600
Prichard, Kern, Orthopoxvirus targets for the development of antiviral therapies, Curr. Drug Targets. Infect. Disord, doi:10.2174/1568005053174627
Rose, Prlić, Altunkaya, Bi, Bradley et al., The RCSB protein data bank: integrative view of protein, gene and 3D structural information, Nucleic Acids Res
Sakano, Takako, Iqbal Mahamood, Yamashita, Molecular dynamics analysis to evaluate docking pose prediction, Biophys. Physicobiol, doi:10.2142/biophysico.13.0
Salentin, Schreiber, Haupt, Adasme, Schroeder, PLIPfully automated protein-ligand interaction profiler, Nucleic Acids Res, doi:10.7490/F1000RESEARCH.1098304.1
Schneidman-Duhovny, Dror, Inbar, Nussinov, Wolfson, Deterministic pharmacophore detection via multiple flexible alignment of drug-like molecules, J. Comput. Biol, doi:10.1089/cmb.2007.0130
Schneidman-Duhovny, Dror, Inbar, Nussinov, Wolfson, PharmaGist: a webserver for ligand-based pharmacophore detection, Nucleic Acids Res, doi:10.1093/nar/gkn187
Schneidman-Duhovny, Inbar, Nussinov, Wolfson, PatchDock and SymmDock : Servers for Rigid and Symmetric Docking, doi:10.1093/nar/gki481
Shen, Cheng, Xu, Li, Tang, Estimation of ADME properties with substructure pattern recognition, J. Chem. Inf. Model, doi:10.1021/ci100104j
Tripathi, Ghosh, Talapatra, Bioavailability prediction of phytochemicals present in Calotropis procera (Aiton) R. Br. by using Swiss-ADME tool, World Sci. News
Trott, Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem, doi:10.1002/jcc.21334
Volunteers, Li, Wu, Guo, Yao et al., Caution on kidney dysfunctions of 2019-nCoV patients, MedRxiv, doi:10.1101/2020.02.08.20021212
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res, doi:10.1038/s41422-020-0282-0
Who, Coronavirus Disease (COVID-19) Situation Dashboard
Wishart, Feunang, Guo, Lo, Marcu et al., DrugBank 5.0: a major update to the DrugBank database for 2018, Nucleic Acids Res, doi:10.1093/nar/gkx1037
Worldometer, Coronavirus Cases, Worldometer, doi:10.1101/2020.01.23.20018549V2
Xu, Cheng, Chen, Du, Li et al., In silico prediction of chemical ames mutagenicity, J. Chem. Inf. Model, doi:10.1021/ci300400a
Xu, Hassounah, Colby-Germinario, Oliveira, Fogarty et al., Purification of Zika virus RNA-dependent RNA polymerase and its use to identify smallmolecule Zika inhibitors, J. Antimicrob. Chemother, doi:10.1093/jac/dkw514
Yang, Lu, Liu, Wang, Zhang et al., Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China, MedRxiv, doi:10.1101/2020.02.10.20021675
Yang, Wang, Chen, Hao, Yang, LARMD : Integration of Bioinformatic Resources to Profile Ligand-driven Protein Dynamics With a Case on the Activation of Estrogen Receptor, doi:10.1093/bib/bbz141
Yuen, Ye, Fung, Chan, Jin, SARS-CoV-2 and COVID-19: the most important research questions, Cell Biosci, doi:10.1186/s13578-020-00404-4
Zhang, Zhou, Binding Mechanism of Remdesivir to SARS-CoV-2 RNA Dependent RNA Polymerase, doi:10.20944/preprints202003.0267.v1
Zhou, Dai, Tong, COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression, J. Antimicrob. Chemother, doi:10.1093/jac/dkaa114
Zumla, Chan, Azhar, Hui, Yuen, Coronaviruses-drug discovery and therapeutic options, Nat. Rev. Drug Discov, doi:10.1038/nrd.2015.37
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