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All Studies   Meta Analysis    Recent:   

Virtual Screening Reveals Potential Anti-Parasitic Drugs Inhibiting the Receptor Binding Domain of SARS-CoV-2 Spike protein

Muthusamy et al., Journal of Virology & Antiviral Research
Jul 2021  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now known with p < 0.00000000001 from 100 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.
3,800+ studies for 60+ treatments. c19ivm.org
In Silico study identifying 32 anti-parisitic compounds effectively inhibiting the RBD of the SARS-CoV-2 spike protein, with ivermectin being one of the top compounds.
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, 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 induced formation of fibrin clots resistant to degradation Vottero, 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 Bifidobacterium which plays 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.
Muthusamy et al., 8 Jul 2021, peer-reviewed, 5 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Virtual Screening Reveals Potential Anti-Parasitic Drugs Inhibiting the Receptor Binding Domain of SARS-CoV-2 Spike protein
Sathya Muthusamy, Hariprabu Gopal, Thiliban Manivarma, Narayan Satya, Prince. R Pradhan, Prabhu, Prince R Prabhu
The 2019's COVID-19 outbreak which spread to over 200 countries across the globe had its origin from the 2002's SARS-CoV-1 epidemic. The corona viruses are single stranded positive sense RNA viruses with 4 structural proteins such as spike(S), membrane(M), envelope(E) and nucleocapsid(N) proteins and 16 non-structural proteins (NSPs). The spike(S) protein is a homo-trimer protruding from the viral surface comprising 2 subunits namely, the S1 and S2 where the S1 subunit consists of the receptor binding domain (RBD) and the S2 subunit consists of the fusion peptide. The spike glycoprotein is considered as the most desired pharmacological target for drug designing, thus blocking the viral entry into the host. Computer-Aided Drug Designing significantly reduces the cost and time in drug discovery compared to the in-vitro methods. Hence in our study, we have performed a virtual screening of the complete set of anti-parasitic drugs using the popular molecular docking tool, Autodock vina with an aim to repurpose the potential hits for the SARS-CoV-2 infection. The repurposed drugs are advantageous for their easy and immediate access owing to their already proven safety records in toxicity and hence are better than novel drugs. Our results revealed 32 anti-parasitic compounds crossing our threshold binding affinity with selamectin, ivermectin, artefenomel, moxidectin, posaconazole, imidocarb, piperaquine, cepharantine, betulinic acid and atovaquone at the top of the list and occupying the three different electrostatic regions in the RBD. Further optimization strategies and in-vitro trials could make our potential anti-parasitic hits, a potential cure for the SARS-CoV-2 infection.
Conflict of Interest The authors declare no conflict of interest. Author Affiliations Top Department of Biotechnology, Anna University, Chennai--600025
References
Adedeji, Severson, Jonsson, Singh, Weiss, Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus Entry That Act by Three Distinct Mechanisms, J Virol, doi:10.1128/JVI.00998-13
Baig, Khaleeq, Syeda, Docking Prediction of Amantadine in the Receptor Binding Domain of Spike Protein of SARS-CoV-2, ACS Pharmacol. Transl Sci, doi:10.1021/acsptsci.0c00172
Basu, Sarkar, Maulik, Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2, Sci Rep, doi:10.1038/s41598-020-74715-4.
Batiha, Alqahtani, Ilesanmi, Saati, El-Mleeh, A vermectin derivatives, pharmacokinetics, therapeutic and toxic dosages, mechanism of action, and their biological effects, Pharmaceuticals, doi:10.3390/ph13080196
Benson, Clark, Karsch-Mizrachi, Lipman, Ostell, None, GenBank. Nucleic Acids Res, doi:10.1093/nar/gku1216.
Berman, Henrick, Nakamura, Announcing the worldwide Protein Data Bank, Nat Struct Biol, doi:10.1038/nsb1203-980.
Boyle, Banck, James, Morley, Vandermeersch, Open Babel: An open chemical toolbox
Caly, Druce, Catton, Jans, Wagstaff, The FDAapproved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res, doi:10.1016/j.antiviral.2020.104787
Chary, Barbuto, Izadmehr, Hayes, Burns, COVID-19: Therapeutics and Their Toxicities, J Med Toxicol, doi:10.1007/s13181-020-00777-5
Dixit, Yadav, Singh, Ivermectin: Potential role as repurposed drug for covid-19, Malaysian J Med Sci, doi:10.21315/mjms2020.27.4.15.
Drożdżal, Rosik, Lechowicz, Machaj, Kotfis, FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy, Drug Resist Updat, doi:10.1016/j.drup.2020.100719
Fan, Wang, Liu, An, Liu, Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model, Chin Med J, doi:10.1097/CM9.0000000000000797
Gaillard, Evaluation of AutoDock and AutoDock Vina on the CASF-2013 Benchmark, J Chem Inf Model, doi:10.1021/acs.jcim.8b00312.
Goodsell, Olson, Automated docking of substrates to proteins by simulated annealing, Proteins Struct. Funct Bioinforma, doi:10.1002/prot.340080302.
Goswami, Bagchi, Molecular Docking study of Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein with Saikosaponin. a Triterpenoid Natural Product, doi:10.26434/chemrxiv.12033774.
Heimfarth, Serafini, Martins-Filho, Pr, Quintans et al., Drug repurposing and cytokine management in response to COVID-19: A review, Int Immunopharmacol, doi:10.1016/j.intimp.2020.106947.
Ibrahim, Abdelmalek, Elshahat, Elfiky, None, prediction, doi:10.1016/j.jinf.2020.02.026
Jaghoori, Bleijlevens, Olabarriaga, Ways to run AutoDock Vina for virtual screening, J Comput Aided Mol Des, doi:10.1007/s10822-016-9900-9.
Khuroo, Chloroquine and hydroxychloroquine in coronavirus disease 2019 (COVID-19). Facts, fiction and the hype: a critical appraisal, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2020.106101
Kim, Chen, Cheng, Gindulyte, He, PubChem 2019 update: Improved access to chemical data, Nucleic Acids Res, doi:10.1093/nar/gky1033.
Li, Hu, Zhang, Yu, ResPRE: High-accuracy protein contact prediction by coupling precision matrix with deep residual neural networks, Bioinformatics, doi:10.1093/bioinformatics/btz291.
Li, Zhang, Bell, Yu, Zhang, Ensembling multiple raw coevolutionary features with deep residual neural networks for contact-map prediction in CASP13, Proteins Struct. Funct Bioinforma, doi:10.1002/prot.25798
Li, Zhao, Zhan, Quantitative proteomics reveals a broadspectrum antiviral property of ivermectin, benefiting for COVID-19 treatment, J Cell Physiol, doi:10.1002/jcp.30055
Liu, Xiao, Chen, He, Niu, Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: Implications for virus fusogenic mechanism and identification of fusion inhibitors, Lancet, doi:10.1016/S0140-6736(04)15788-7
Mahmoud, Shitu, Mostafa, Drug repurposing of nitazoxanide: can it be an effective therapy for COVID-19?, J Genet Eng Biotechnol, doi:10.1186/s43141-020-00055-5
Mckee, Sternberg, Stange, Laufer, Naujokat, Since
Mudatsir, Yufika, Nainu, Frediansyah, Megawati, Antiviral activity of ivermectin against SARS-CoV-2: An old-fashioned dog with a new trick-A literature review, Sci Pharm
Muthusamy, Gopal, Manivarma, Pradhan, Prabhu, Virtual Screening Reveals Potential Anti-Parasitic Drugs Inhibiting the Receptor Binding Domain of SARS-CoV-2 Spike protein, J Virol Antivir Res
Nguyen, Nguyen, Pham, Huy, Bay, Autodock Vina Adopts More Accurate Binding Poses but Autodock4 Forms Better Binding Affinity, J Chem Inf Model, doi:10.1021/acs.jcim.9b00778.
Othman, Bouslama, Brandenburg, Da Rocha, Hamdi, Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: Similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism, Biochem Biophys Res Commun, doi:10.1016/j.bbrc.2020.05.028
Pagadala, Syed, Tuszynski, Software for molecular docking: a review, Biophys Rev, doi:10.1007/s12551-016-0247-1
Pandey, Rane, Chatterjee, Kumar, Khan, Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: an in silico study for drug development, J Biomol Struct Dyn, doi:10.1080/07391102.2020.1796811
Papich, None, Doramectin. Saunders Handb Vet Drugs, doi:10.1016/b978-0-323-24485-5.00228-x.
Peña-Silva, Duffull, Steer, Jaramillo-Rincon, Gwee, Pharmacokinetic considerations on the repurposing of ivermectin for treatment of COVID-19, Br J Clin Pharmacol, doi:10.1111/bcp.14476
Pink, Hudson, Mouriès, Bendig, Opportunities and challenges in antiparasitic drug discovery, Nat Re Drug Discov, doi:10.1038/nrd1824.
Prieto-Martínez, Arciniega, Medina-Franco, Acoplamiento Molecular: Avances Recientes y Retos, TIP Rev Espec En Ciencias Químico-Biológicas, doi:10.22201/fesz.23958723e.2018.0.143.
Roy, Kucukural, Zhang, I-TASSER: A unified platform for automated protein structure and function prediction, Nat Protoc, doi:10.1038/nprot.2010.5.
Saxena, Drug targets for COVID-19 therapeutics: Ongoing global efforts, J Biosci, doi:10.1007/s12038-020-00067-w.
Sethi, Joshi, Sasikala, Alvala, Molecular Docking in Modern Drug Discovery: Principles and Recent Applications, Drug Discov Dev New Adv, doi:10.5772/intechopen.85991.
Tahir Ul Qamar, Alqahtani, Alamri, Chen, Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants, J Pharm Anal, doi:10.1016/j.jpha.2020.03.009.
Tiwari, Beer, Sankaranarayanan, Swanson-Mungerson, Desai, Discovering small-molecule therapeutics against SARS-CoV, doi:10.1016/j.drudis.2020.06.017
Ton, Gentile, Hsing, Ban, Cherkasov, Rapid Identification of Potential Inhibitors of SARS-CoV-2 Main Protease by Deep Docking of 1.3 Billion Compounds, Mol Inform, doi:10.1002/minf.202000028
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.
Unni, Aouti, Balasundaram, Identification of a Potent Inhibitor Targeting the Spike Protein of Pandemic Human Coronavirus, SARS-CoV-2 by Computational Methods, doi:10.26434/chemrxiv.12197934
Vieira, Sousa, Comparing AutoDock and Vina in ligand/decoy discrimination for virtual screening, Appl Sci, doi:10.3390/app9214538
Wishart, Feunang, Guo, Lo, Marcu, J DrugBank 5.0: A major update to the DrugBank database for 2018, Nucleic Acids Res, doi:10.1093/nar/gkx1037.
Wu, Skolnick, Zhang, Ab initio modeling of small proteins by iterative TASSER simulations, BMC Biol, doi:10.1186/1741-7007-5-17
Xia, Liu, Wang, Xu, Lan, Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion, Cell Res, doi:10.1038/s41422-020-0305-x.
Xu, Zhang, How significant is a protein structure similarity with TMscore = 0.5?, Bioinformatics, doi:10.1093/bioinformatics/btq066
Yang, Sun, Li, Liu, Tang, Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and, Structural Alerts Front Chem, doi:10.3389/fchem.2018.00030.
Yang, Yan, Roy, Xu, Poisson, The I-TASSER suite: Protein structure and function prediction, Nat Methods, doi:10.1038/nmeth.3213.
Yang, Zhang, I-TASSER server: New development for protein structure and function predictions, Nucleic Acids Res, doi:10.1093/nar/gkv342.
Yang, Zhang, Protein Structure and Function Prediction Using I-TASSER, Curr Protoc Bioinforma, doi:10.1002/0471250953.bi0508s52
Yuan, Chan, Hu, Using PyMOL as a platform for computational drug design, Wiley Interdiscip. Rev Comput Mol Sci, doi:10.1002/wcms.1298.
Zhang, I-TASSER server for protein 3D structure prediction, BMC Bioinformatics, doi:10.1186/1471-2105-9-40
Zhang, Skolnick, Scoring function for automated assessment of protein structure template quality, Proteins Struct Funct Genet, doi:10.1002/prot.20264
Zhang, Zheng, Huang, Bell, Zhou, Protein Structure and Sequence Reanalysis of 2019-nCoV Genome Refutes Snakes as Its Intermediate Host and the Unique Similarity between Its Spike Protein Insertions and HIV-1, J Proteome Res, doi:10.1021/acs.jproteome.0c00129
Zheng, Li, Zhang, Pearce, Mortuza, Deep-learning contact-map guided protein structure prediction in CASP13, Proteins Struct Funct Bioinforma, doi:10.1002/prot.25792
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