346
Views
3
CrossRef citations to date
0
Altmetric
Research Articles

Molecular dynamics simulation, 3D-pharmacophore and scaffold hopping analysis in the design of multi-target drugs to inhibit potential targets of COVID-19

ORCID Icon, , ORCID Icon, & ORCID Icon
Pages 11787-11808 | Received 29 Oct 2020, Accepted 30 Jul 2021, Published online: 18 Aug 2021

References

  • Accelrys. (2009). Accelrys Discovery Studio 2.5. Accelrys.
  • Alexpandi, R., Mesquita, J. F. D., Pandian, S. K., & Ravi, A. V. (2020). Quinolines-based SARS-CoV-2 3CLpro and RdRp inhibitors and spike-RBD-ACE2 inhibitor for drug-repurposing against COVID-19: An in silico analysis. Frontiers in Microbiology, 11, 1796–1811. https://doi.org/10.3389/fmicb.2020.01796
  • Arabi, Y. M., Fowler, R., & Hayden, F. G. (2020). Critical care management of adults with community-acquired severe respiratory viral infection. Intensive Care Medicine, 46(2), 315–328. https://doi.org/10.1007/s00134-020-05943-5
  • Balaramnavar, V. M., Ahmad, K., Saeed, M., Ahmad, I., Kamal, M., & Jawed, T. (2020). Pharmacophore-based approaches in the rational repurposing technique for FDA approved drugs targeting SARS-CoV-2 Mpro. RSC Advances, 10(66), 40264–40275. https://doi.org/10.1039/D0RA06038K
  • Cannalire, R., Cerchia, C., Beccari, A. R., & Di Leva, F. S. (2020). Targeting SARS-CoV-2 proteases and polymerase for COVID-19 treatment: State of the art and future opportunities. Journal of Medicinal Chemistry.
  • Cava, C., Bertoli, G., & Castiglioni, I. (2020). In silico discovery of candidate drugs against Covid-19. Viruses, 12, 404–418. https://doi.org/10.3390/v12040404
  • Centers for Disease Control and Prevention. (2020). Retrived May 10, 2020, from https://www.cdc.gov/coronavirus/types.html
  • Chenthamarakshan, V., Das, P., Hoffman, S. C., Strobelty, H., Padhi, I., Lim, K. W., Hoovery, B., Manicaz, M., Bornz, J., Lainoz, T., & Mojsilovic, A. (2020). CogMol: Target-specific and selective drug design for COVID-19 using deep generative models. arXiv preprint, arXiv:2004.01215.
  • Chu, C. M., Cheng, V. C., Hung, I. F., Wong, M. M., Chan, K. H., & Chan, K. S. (2004). Role of lopinavir/ritonavir in thetreatment of SARS: Initial virological and clinical findings. Thorax, 59(3), 252–256. https://doi.org/10.1136/thorax.2003.012658
  • Costanzo, M., De Giglio, M., & Roviello, G. N. (2020). SARS-CoV-2: Recent reports on antiviral therapies based on lopinavir/ritonavir, darunavir/umifenovir, hydroxychloroquine, remdesivir, favipiravir and other drugs for the treatment of the new coronavirus. Current Medicinal Chemistry, 27(27), 4536–4541. https://doi.org/10.2174/0929867327666200416131117
  • de Wilde, A. H., Jochmans, D., Posthuma, C. C., Zevenhoven-Dobbe, J. C., van Nieuwkoop, S., Bestebroer, T. M., van den Hoogen, B. G., Neyts, J., & Snijder, E. J. (2014). Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrobial Agents and Chemotherapy, 58(8), 4875–4884. https://doi.org/10.1128/AAC.03011-14
  • Dyall, J., Coleman, C. M., Hart, B. J., Venkataraman, T., Holbrook, M. R., Kindrachuk, J., Johnson, R. F., Olinger, G. G., Jahrling, P. B., Laidlaw, M., Johansen, L. M., Lear-Rooney, C. M., Glass, P. J., Hensley, L. E., & Frieman, M. B. (2014). Repurposing of clinically developed drugs for treatment of Middle East Respiratory Syndrome coronavirus infection. Antimicrobial Agents and Chemotherapy, 58(8), 4885–4893. https://doi.org/10.1128/AAC.03036-14
  • Elfiky, A. A. (2020). Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sciences, 248, 117477. https://doi.org/10.1016/j.lfs.2020.117477
  • Elfiky, A. A. (2021). SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: An in silico perspective. Journal of Biomolecular Structure and Dynamics, 39(9), 3204–3212.
  • Fayyazi, N., Esmaeili, S., Taheri, S., Ghasemi, J. B., & Scotti, L. (2019). Pharmacophore modeling, synthesis, scaffold hopping and biological β-Hematin inhibition interaction studies for anti-malaria compounds. Current Topics in Medicinal Chemistry, 142, 94–113.
  • Fayyazi, N., Fassihi, A., Esmaeili, S., Taheri, S., Ghasemi, J. B., & Saghaie, L. (2020). Molecular dynamics simulation and 3D-pharmacophore analysis of new quinoline-based analogues with dual potential against EGFR and VEGFR-2. International Journal of Biological Macromolecules, 142, 94–101. https://doi.org/10.1016/j.ijbiomac.2019.09.077
  • 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., … Rao, Z. (2020). Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science (New York, N.Y.), 368(6492), 779–782. https://doi.org/10.1126/science.abb7498
  • Gong, P., & Peersen, O. B. (2010). Structural basis for active site closure by the poliovirus RNA-dependent RNA polymerase. Proceedings of the National Academy of Sciences of the United States of America, 107(52), 22505–22510. https://doi.org/10.1073/pnas.1007626107
  • Grzybowski, B. A., Ishchenko, A. V., Shimada, J., & Shakhnovich, E. I. (2002). From knowledge-based potentials to combinatorial lead design in silico. Accounts of Chemical Research, 35(5), 261–269. https://doi.org/10.1021/ar970146b
  • Gupta, S., Fallarero, A., Järvinen, P., Karlsson, D., Johnson, M. S., Vuorela, P. S., & Mohan, C. G. (2011). Discovery of dual binding site acetylcholinesterase inhibitors identified by pharmacophore modeling and sequential virtual screening techniques. Bioorganic & Medicinal Chemistry Letters, 21(4), 1105–1112. https://doi.org/10.1016/j.bmcl.2010.12.131
  • Harrison, C. (2020). Coronavirus puts drug repurposing on the fast track. Nature Biotechnology, 38(4), 379–391. https://doi.org/10.1038/d41587-020-00003-1
  • Hauke, J., Achter, S., & Meyer, M. (2020). Theory development via replicated simulations and the added value of standards. Journal of Artificial Societies and Social Simulation, 23(1), 12. https://doi.org/10.18564/jasss.4219
  • Hoffman, R. L., Kania, R. S., Brothers, M. A., Davies, J. F., Ferre, R. A., Gajiwala, K. S., He, M., Hogan, R. J., Kozminski, K., Li, L. Y., Lockner, J. W., Lou, J., Marra, M. T., Mitchell, L. J., Murray, B. W., Nieman, J. A., Noell, S., Planken, S. P., Rowe, T., … Taggart, B. (2020). Discovery of ketone-based covalent inhibitors of coronavirus 3CL proteases for the potential therapeutic treatment of COVID-19. Journal of Medicinal Chemistry, 63(21), 12725–12747. https://doi.org/10.1021/acs.jmedchem.0c01063
  • Horvath, D., Orlov, A., Osolodkin, D. I., Ishmukhametov, A. A., Marcou, G., & Varnek, A. (2020). A chemographic audit of anti-coronavirus structure-activity information from public databases (ChEMBL). Molecular Informatics, 39(12), 2000080. https://doi.org/10.1002/minf.202000080
  • Huang, J., Song, W., Huang, H., & Sun, Q. (2020). Pharmacological therapeutics targeting RNA-dependent RNA polymerase, proteinase and spike protein: FROM mechanistic studies to clinical trials for COVID-19. Journal of Clinical Medicine, 9, 1131. https://doi.org/10.3390/jcm9041131
  • Iftikhar, H., Ali, H. N., Farooq, S., Naveed, H., & Shahzad-Ul-Hussan, S. (2020). Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach. Computers in Biology and Medicine, 122, 103848–103856. https://doi.org/10.1016/j.compbiomed.2020.103848
  • Kandeel, M., & Al-Nazawi, M. (2020). Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease. Life Sciences, 251, 117627. https://doi.org/10.1016/j.lfs.2020.117627
  • Kirchdoerfer, R. N., & Ward, A. B. (2019). Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nature Communications, 10(1), 2342–2342. https://doi.org/10.1038/s41467-019-10280-3
  • Kokic, G., Hillen, H. S., Tegunov, D., Dienemann, C., Seitz, F., Schmitzova, J., Farnung, L., Siewert, A., Höbartner, C., & Cramer, P. (2021). Mechanism of SARS-CoV-2 polymerase stalling by remdesivir. Nature Communications, 12(1), 279–279. https://doi.org/10.1038/s41467-020-20542-0
  • Kumar, V., Tan, K.-P., Wang, Y.-M., Lin, S.-W., & Liang, P.-H. (2016). Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors. Bioorganic & Medicinal Chemistry, 24(13), 3035–3042. https://doi.org/10.1016/j.bmc.2016.05.013
  • Kumar, Y., Singh, H., & Patel, C. N. (2020). In silico prediction of potential inhibitors for the Main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing. Journal of Infection and Public Health, 13(9), 1210–1223. https://doi.org/10.1016/j.jiph.2020.06.016
  • Li, G., & Clercq, E. (2020). Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nature Reviews. Drug Discovery, 19(3), 149–150. https://doi.org/10.1038/d41573-020-00016-0
  • Li, R., Su, X., Chen, Z., Huang, W., Wang, Y., Wang, K., Lin, B., Wang, J., & Cheng, M. (2015). Structure-based virtual screening and ADME/T-based profiling for low molecular weight chemical starting points as p21 activated kinase 4 inhibitors. RSC Advances, 5(30), 23202–23232. https://doi.org/10.1039/C4RA16963H
  • Li, X., He, Z., Chen, L., Li, Y., Li, Q., Zhao, S., Tao, Z., Hu, W., Qin, L., & Chen, X. (2011). Synergy of the antiretroviral protease inhibitor indinavir and chloroquine against malaria parasites in vitro and in vivo. Parasitology Research, 109(6), 1519–1524. https://doi.org/10.1007/s00436-011-2427-z
  • Liang-Qin, G., Jing, X. U., & Shao-Dong, C. (2020). In silico screening of potential chinese herbal medicine against COVID-19 by targeting SARS-CoV-2 3CLpro and angiotensin converting enzyme II using molecular docking. Chinese Journal of Integrative Medicine, 26, 527–532.
  • Lipinski, C. A. (2004). Lead- and drug-like compounds: The rule-of-five revolution. Drug Discovery Today. Technologies, 1(4), 337–341.
  • Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Wang, W., Song, H., Huang, B., Zhu, N., Bi, Y., Ma, X., Zhan, F., Wang, L., Hu, T., Zhou, H., Hu, Z., Zhou, W., Zhao, L., … Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet (London, England), 395(10224), 565–574. https://doi.org/10.1016/S0140-6736(20)30251-8
  • Ma, X. H., Wang, R., Yang, S. Y., Li, Z. R., Xue, Y., Wei, Y. C., Low, B. C., Chen, Y. Z. (2008). Evaluation of virtual screening performance of support vector machines trained by sparsely distributed active compounds. Journal of Chemical Information and Modeling, 48, 1227–1237. https://doi.org/10.1016/j.ddtec.2004.11.007
  • Macchiagodena, M., Pagliai, M., & Procacci, P. (2020). Identification of potential binders of the main protease 3CLpro of the COVID-19 via structure-based ligand design and molecular modeling. Chemical Physics Letters, 750, 137489–137493. https://doi.org/10.1016/j.cplett.2020.137489
  • Madelain, V., Guedj, J., Mentré, F., Huyen Nguyen, T. T., Jacquot, F., & Oestereich, L. (2017). Favipiravir Pharmacokinetics in Nonhuman Primates and Insights for Future Efficacy Studies of Hemorrhagic Fever Viruses. Antimicrobial Agents and Chemotherapy, 61, e01305-16. https://doi.org/10.1128/AAC.01305-16
  • Mansour, M. A., AboulMagd, A. M., & Abdel-Rahman, H. M. (2020). Quinazoline-Schiff base conjugates: In silico study and ADMET predictions as multitarget inhibitors of coronavirus (SARS-CoV-2) proteins. RSC Advances, 10(56), 34033–34045. https://doi.org/10.1039/D0RA06424F
  • Maurya, V. K., Kumar, S., Bhatt, L. B., & Saxena, S. K. (2020). Antiviral activity of traditional medicinal plants from Ayurveda against SARS-CoV-2 infection. Journal of Biomolecular Structure and Dynamics, 2020, 1–17.
  • Mc Tigue, M., Murray, B. W., Chen, J. H., Deng, Y. L., Solowiej, J., & Kania, R. S. (2012). Molecular conformations, interactions, and properties associated with drug efficiency and clinical performance among VEGFR TK inhibitors. Proceedings of the National Academy of Sciences of the United States of America, 109(45), 18281–18289. https://doi.org/10.1073/pnas.1207759109
  • Muralidharan, N., Sakthivel, R., Velmurugan, D., & Gromiha, M. M. (2020). Computational studies of drug repurposing and synergism of lopinavir, oseltamivir and ritonavir binding with SARS-CoV-2 Protease against COVID-19. Journal of Biomolecular Structure and Dynamics, 16, 1–6.
  • Ntie-Kang, F. (2013). An in silico evaluation of the ADMET profile of the Streptome DB database. Springer Plus, 2, 353. https://doi.org/10.1186/2193-1801-2-353
  • Ngo, S. T., Pham, N. Q. A., Le, L. T., Pham, D., & Vu, V. V. (2020). Computational determination of potential inhibitors of SARS-CoV-2 main protease. Journal of Chemical Information and Modeling, 60(12), 5771–5780. https://doi.org/10.1021/acs.jcim.0c00491
  • Nosengo, N. (2016). Can you teach old drugs new tricks? Nature, 534(7607), 314–316. https://doi.org/10.1038/534314a
  • Pammolli, F., Magazzini, L., & Riccaboni, M. (2011). The productivity crisis in pharmaceutical R&D. Nature Reviews. Drug Discovery, 10(6), 428–438. https://doi.org/10.1038/nrd3405
  • Pant, S., Singh, M., Ravichandiran, V., Murty, U. S. N., & Srivastav, H. K. (2020). Peptide-like and small-molecule inhibitors against Covid-19. Journal of Biomolecular Structure and Dynamics. https://doi.org/10.1080/07391102.2020.1757510
  • Pushpakom, S., Iorio, F., Eyers, P. A., Escott, K. J., Hopper, S., Wells, A., Doig, A., Guilliams, T., Latimer, J., McNamee, C., Norris, A., Sanseau, P., Cavalla, D., & Pirmohamed, M. (2019). Drug repurposing: Progress, challenges and recommendations. Nature Reviews. Drug Discovery, 18(1), 41–58. https://doi.org/10.1038/nrd.2018.168
  • Saeed, M., Saeed, A., Alam, M. J., & Alreshidi, M. (2021). Receptor-based pharmacophore modeling in the search for natural products for COVID-19 Mpro. Molecules, 26, 1549. https://doi.org/10.3390/molecules26061549
  • Sisk, J. M., & Frieman, M. B. (2015). Screening of FDA-approved drugs for treatment of emerging pathogens. ACS Infectious Diseases, 1(9), 401–402. https://doi.org/10.1021/acsinfecdis.5b00089
  • Sneha, P., Tyagi, A., Jose, V., Jane, M., Krishna, K., & Gopi, M. C. (2016). Integration of common feature pharmacophore modeling and in vitro study to identify potent AChE inhibitors. Medicinal Chemistry Research, 25(12), 2965–2975. https://doi.org/10.1007/s00044-016-1716-6
  • Stamos, J., Sliwkowski, M. X., & Eigenbrot, C. (2002). Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. The Journal of Biological Chemistry, 277(48), 46265–46272. https://doi.org/10.1074/jbc.M207135200
  • Stasiulewicz, A., Maksymiuk, A. W., Nguyen, M. L., Bełza, B., & Sulkowska, J. I. (2021). SARS-CoV-2 papain-like protease potential inhibitors—In silico quantitative assessment. International Journal of Molecular Sciences, 22, 3957–3987. https://doi.org/10.3390/ijms22083957
  • Sunseri, J., & Koes, D. R. (2016). Pharmit: Interactive exploration of chemical space. Nucleic Acids Research, 44, 442–448. https://doi.org/10.1093/nar/gkw287
  • U.S. Food and Drug Administration. (2021). Retrieved June 18, 2021, from https://www.fda.gov/media/137564/download
  • Ugale, V. G., Patel, H. M., & Surana, S. J. (2017). Molecular modeling studies of quinoline derivatives as VEGFR-2 tyrosine kinase inhibitors using pharmacophore based 3-D QSAR and docking approach. The Arabian Journal of Chemistry, 10, 1980–2003.
  • Vincent, M. J., Bergeron, E., Benjannet, S., Erickson, B. R., Rollin, P. E., Ksiazek, T. G., Seidah, N. G., & Nichol, S. T. (2005). Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virology Journal, 2, 69. https://doi.org/10.1186/1743-422X-2-69
  • Wang, J. (2020). Fast identification of possible drug treatment of coronavirus disease-19 (COVID-19) through computational drug repurposing study. Journal of Chemical Information and Modeling, 60(6), 3277–3286. https://doi.org/10.1021/acs.jcim.0c00179
  • 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 Research, 30(3), 269–277. https://doi.org/10.1038/s41422-020-0282-0
  • Warren, T. K., Jordan, R., Lo, M. K., Ray, A. S., Mackman, R. L., Soloveva, V., Siegel, D., Perron, M., Bannister, R., Hui, H. C., Larson, N., Strickley, R., Wells, J., Stuthman, K. S., Van Tongeren, S. A., Garza, N. L., Donnelly, G., Shurtleff, A. C., Retterer, C. J., … Bavari, S. (2016). Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature, 531(7594), 381–385. https://doi.org/10.1038/nature17180
  • WHO. (2021a). WHO coronavirus disease (COVID-19) dashboard. Retrieved June 18, 2021, from https://who.sprinklr.com/
  • WHO. (2021b). World Health Organization website. Retrieved June 18, 2021, from https://www.who.int/
  • Zhang, L., & Zhou, R. (2020). Binding mechanism of remdesivir to SARS-CoV-2 RNA Dependent RNA Polymerase, preprints. https://doi.org/10.20944/preprints202003.0267.v1
  • Zhang, L., Lin, D., Sun, X., Curth, U., Drosten, C., Sauerhering, L., Becker, S., Rox, K., & Hilgenfeld, R. (2020). Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science (New York, N.Y.), 368(6489), 409–412. https://doi.org/10.1126/science.abb3405
  • Zhang, W., Pei, J., & Lai, L. (2017). Computational multitarget drug design. Journal of Chemical Information and Modeling, 57(3), 403–412. https://doi.org/10.1021/acs.jcim.6b00491

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.