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Research Articles

De novo generation of dual-target ligands for the treatment of SARS-CoV-2 using deep learning, virtual screening, and molecular dynamic simulations

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Pages 3019-3029 | Received 26 Dec 2022, Accepted 30 Apr 2023, Published online: 14 Jul 2023

References

  • Abdel-Basset, M., Hawash, H., Elhoseny, M., Chakrabortty, R. K., & Ryan, M. (2020). DeepH-DTA: Deep learning for predicting drug-target interactions: A case study of COVID-19 drug repurposing. IEEE Access: Practical Innovations, Open Solutions, 8, 170433–170451. https://doi.org/10.1109/ACCESS.2020.3024238
  • Anighoro, A., Bajorath, J., & Rastelli, G. (2014). Polypharmacology: Challenges and opportunities in drug discovery: Miniperspective. Journal of Medicinal Chemistry, 57(19), 7874–7887. https://doi.org/10.1021/jm5006463
  • Arús-Pous, J., Blaschke, T., Ulander, S., Reymond, J.-L., Chen, H., & Engkvist, O. (2019). Exploring the GDB-13 chemical space using deep generative models. Journal of Cheminformatics, 11(1), 20. https://doi.org/10.1186/s13321-019-0341-z
  • Bajusz, D., Rácz, A., & Héberger, K. (2015). Why is Tanimoto index an appropriate choice for fingerprint-based similarity calculations? Journal of Cheminformatics, 7(1), 20. https://doi.org/10.1186/s13321-015-0069-3
  • Benhenda, M. (2018). Can AI reproduce observed chemical diversity? bioRxiv, 292177.
  • Bharadwaj, S., Lee, K. E., Dwivedi, V. D., Yadava, U., Panwar, A., Lucas, S. J., Pandey, A., & Kang, S. G. (2019). Discovery of Ganoderma lucidum triterpenoids as potential inhibitors against Dengue virus NS2B-NS3 protease. Scientific Reports, 9(1), 1–12. https://doi.org/10.1038/s41598-019-55723-5
  • Bolognesi, M. L., & Cavalli, A. (2016). Multitarget drug discovery and polypharmacology (Vol. 11, pp. 1190–1192). Wiley Online Library. https://doi.org/10.1002/cmdc.201600161
  • Bung, N., Krishnan, S. R., Bulusu, G., & Roy, A. (2021). De novo design of new chemical entities for SARS-CoV-2 using artificial intelligence. Future Medicinal Chemistry, 13(6), 575–585. https://doi.org/10.4155/fmc-2020-0262
  • Cannalire, R., Cerchia, C., Beccari, A. R., Di Leva, F. S., & Summa, V. (2022). Targeting SARS-CoV-2 proteases and polymerase for COVID-19 treatment: State of the art and future opportunities. Journal of Medicinal Chemistry, 65(4), 2716–2746. https://doi.org/10.1021/acs.jmedchem.0c01140
  • Chen, F., Liu, H., Sun, H., Pan, P., Li, Y., Li, D., & Hou, T. (2016). Assessing the performance of the MM/PBSA and MM/GBSA methods. 6. Capability to predict protein–protein binding free energies and re-rank binding poses generated by protein–protein docking. Physical Chemistry Chemical Physics : PCCP, 18(32), 22129–22139. https://doi.org/10.1039/c6cp03670h
  • Chen, H., Wei, P., Huang, C., Tan, L., Liu, Y., & Lai, L. (2006). Only one protomer is active in the dimer of SARS 3C-like proteinase. The Journal of Biological Chemistry, 281(20), 13894–13898. https://doi.org/10.1074/jbc.M510745200
  • Chenthamarakshan, V., Das, P., Hoffman, S., Strobelt, H., Padhi, I., Lim, K. W., … Laino, T. (2020). CogMol: Target-specific and selective drug design for COVID-19 using deep generative models. Advances in Neural Information Processing Systems, 33, 4320–4332.
  • Choubey, A., Dehury, B., Kumar, S., Medhi, B., & Mondal, P. (2022). Naltrexone a potential therapeutic candidate for COVID-19. Journal of Biomolecular Structure and Dynamics. 15, 1–8.
  • Cireşan, D. C., Meier, U., & Schmidhuber, J. (2012). Transfer learning for Latin and Chinese characters with deep neural networks [Paper presentation]. The 2012 International Joint Conference on Neural Networks (IJCNN).
  • Cucinotta, D., & Vanelli, M. (2020). WHO declares COVID-19 a pandemic. Acta Bio Medica: Atenei Parmensis, 91(1), 157.
  • Davies, M., Nowotka, M., Papadatos, G., Dedman, N., Gaulton, A., Atkinson, F., Bellis, L., & Overington, J. P. (2015). ChEMBL web services: Streamlining access to drug discovery data and utilities. Nucleic Acids Research, 43(W1), W612–W620. https://doi.org/10.1093/nar/gkv352
  • Deb, K., Pratap, A., Agarwal, S., & Meyarivan, T. (2002). A fast and elitist multiobjective genetic algorithm: NSGA-II. IEEE Transactions on Evolutionary Computation, 6(2), 182–197. https://doi.org/10.1109/4235.996017
  • Devi, R. V., Sathya, S. S., & Coumar, M. S. (2015). Evolutionary algorithms for de novo drug design–A survey. Applied Soft Computing, 27, 543–552. https://doi.org/10.1016/j.asoc.2014.09.042
  • Edwards, I. R., & Aronson, J. K. (2000). Adverse drug reactions: Definitions, diagnosis, and management. Lancet (London, England), 356(9237), 1255–1259. https://doi.org/10.1016/S0140-6736(00)02799-9
  • Ertl, P., Lewis, R., Martin, E., & Polyakov, V. (2017). In silico generation of novel, drug-like chemical matter using the LSTM neural network. arXiv preprint arXiv:1712.07449
  • Fischer, T., Gazzola, S., & Riedl, R. (2019). Approaching target selectivity by de novo drug design. Expert Opinion on Drug Discovery, 14(8), 791–803. https://doi.org/10.1080/17460441.2019.1615435
  • Goldberg, Y. (2016). A primer on neural network models for natural language processing. Journal of Artificial Intelligence Research, 57, 345–420. https://doi.org/10.1613/jair.4992
  • Graves, A. (2013). Generating sequences with recurrent neural networks. arXiv Preprint arXiv:1308.0850,
  • Gupta, R. K., Nwachuku, E. L., Zusman, B. E., Jha, R. M., & Puccio, A. M. (2021). Drug repurposing for COVID-19 based on an integrative meta-analysis of SARS-CoV-2 induced gene signature in human airway epithelium. PloS One, 16(9), e0257784. https://doi.org/10.1371/journal.pone.0257784
  • Hochreiter, S., & Schmidhuber, J. (1997). Long short-term memory. Neural Computation, 9(8), 1735–1780. https://doi.org/10.1162/neco.1997.9.8.1735
  • Humayun, F., Cai, Y., Khan, A., Farhan, S. A., Khan, F., Rana, U. I., binte Qamar, A., Fawad, N., Shamas, S. (2021). Structure-guided design of multi-epitopes vaccine against variants of concern (VOCs) of SARS-CoV-2 and validation through In silico cloning and immune simulations.Computers in Biology and Medicine, 140, 105122. https://doi.org/10.1016/j.compbiomed.2021.105122
  • Jastrzębski, S., Leśniak, D., & Czarnecki, W. M. (2016). Learning to smile (s). arXiv preprint arXiv:1602.06289
  • Jin, Z., Du, X., Xu, Y., Deng, Y., Liu, M., Zhao, Y., Zhang, B., Li, X., Zhang, L., Peng, C., Duan, Y., Yu, J., Wang, L., Yang, K., Liu, F., Jiang, R., Yang, X., You, T., Liu, X., … Yang, H. (2020). Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature, 582(7811), 289–293. https://doi.org/10.1038/s41586-020-2223-y
  • Kingma, D. P. (2015). & Ba J.(2014). Adam: A method for stochastic optimization. arXiv preprint arXiv:1412.6980
  • Klebe, G. (2000). Recent developments in structure-based drug design. Journal of Molecular Medicine (Berlin, Germany), 78(5), 269–281. https://doi.org/10.1007/s001090000084
  • L Bolognesi, M. (2013). Polypharmacology in a single drug: Multitarget drugs. Current Medicinal Chemistry, 20(13), 1639–1645.
  • Landrum, G. (2016). RDKit: open-source cheminformatics. http://www. rdkit. org. Google Scholar There is no corresponding record for this reference.
  • Li, C., Wang, J., Niu, Z., Yao, J., & Zeng, X. (2021). A spatial-temporal gated attention module for molecular property prediction based on molecular geometry. Briefings in Bioinformatics, 22(5), bbab078. https://doi.org/10.1093/bib/bbab078
  • Li, C., Wei, W., Li, J., Yao, J., Zeng, X., & Lv, Z. (2022). 3DMol-Net: Learn 3D molecular representation using adaptive graph convolutional network based on rotation invariance. IEEE Journal of Biomedical and Health Informatics, 26(10), 5044–5054. https://doi.org/10.1109/JBHI.2021.3089162
  • Liu, Y., Liang, C., Xin, L., Ren, X., Tian, L., Ju, X., Li, H., Wang, Y., Zhao, Q., Liu, H., Cao, W., Xie, X., Zhang, D., Wang, Y., & Jian, Y. (2020). The development of Coronavirus 3C-Like protease (3CLpro) inhibitors from 2010 to 2020. European Journal of Medicinal Chemistry, 206, 112711. https://doi.org/10.1016/j.ejmech.2020.112711
  • Majumdar, S., Nandi, S. K., Ghosal, S., Ghosh, B., Mallik, W., Roy, N. D., Biswas, A., Mukherjee, S., Pal, S., & Bhattacharyya, N. (2021). Deep learning-based potential ligand prediction framework for COVID-19 with drug–target interaction model. Cognitive Computation, 1–13. https://doi.org/10.1007/s12559-021-09840-x
  • Mitchell, J. B. (2014). Machine learning methods in chemoinformatics. Wiley Interdisciplinary Reviews. Computational Molecular Science, 4(5), 468–481. https://doi.org/10.1002/wcms.1183
  • Mohs, R. C., & Greig, N. H. (2017). Drug discovery and development: Role of basic biological research. Alzheimer’s & Dementia (New York, N. Y.), 3(4), 651–657. https://doi.org/10.1016/j.trci.2017.10.005
  • Morgan, H. L. (1965). The generation of a unique machine description for chemical structures-a technique developed at chemical abstracts service. Journal of Chemical Documentation, 5(2), 107–113. https://doi.org/10.1021/c160017a018
  • Nicolaou, C. A., Apostolakis, J., & Pattichis, C. S. (2009). De novo drug design using multiobjective evolutionary graphs. Journal of Chemical Information and Modeling, 49(2), 295–307. https://doi.org/10.1021/ci800308h
  • O’Hagan, S., & Kell, D. B. (2018). Analysing and navigating natural products space for generating small, diverse, but representative chemical libraries. Biotechnology Journal, 13(1), 1700503. https://doi.org/10.1002/biot.201700503
  • Olivecrona, M., Blaschke, T., Engkvist, O., & Chen, H. (2017). Molecular de-novo design through deep reinforcement learning. Journal of Cheminformatics, 9(1), 1–14. https://doi.org/10.1186/s13321-017-0235-x
  • Pastorino, R., Pezzullo, A. M., Villani, L., Causio, F. A., Axfors, C., Contopoulos-Ioannidis, D. G., Boccia, S., & Ioannidis, J. P. A. (2022). Change in age distribution of COVID-19 deaths with the introduction of COVID-19 vaccination. Environmental Research, 204(Pt C), 112342. https://doi.org/10.1016/j.envres.2021.112342
  • Paszke, A., Gross, S., Chintala, S., Chanan, G., Yang, E., DeVito, Z., … Lerer, A. (2017). Automatic differentiation in pytorch.
  • Peters, J.-U. (2013). Polypharmacology–foe or friend? Journal of Medicinal Chemistry, 56(22), 8955–8971. https://doi.org/10.1021/jm400856t
  • Petushkova, A. I., & Zamyatnin, A. A. Jr, (2020). Papain-like proteases as coronaviral drug targets: Current inhibitors, opportunities, and limitations. Pharmaceuticals, 13(10), 277. https://doi.org/10.3390/ph13100277
  • Pillaiyar, T., Manickam, M., Namasivayam, V., Hayashi, Y., & Jung, S.-H. (2016). An overview of severe acute respiratory syndrome–coronavirus (SARS-CoV) 3CL protease inhibitors: peptidomimetics and small molecule chemotherapy. Journal of Medicinal Chemistry, 59(14), 6595–6628. https://doi.org/10.1021/acs.jmedchem.5b01461
  • Rahman, M. M., Saha, T., Islam, K. J., Suman, R. H., Biswas, S., Rahat, E. U., Hossen, M. R., Islam, R., Hossain, M. N., Mamun, A. A., Khan, M., Ali, M. A., & Halim, M. A. (2021). Virtual screening, molecular dynamics and structure–activity relationship studies to identify potent approved drugs for Covid-19 treatment. Journal of Biomolecular Structure & Dynamics, 39(16), 6231–6241. https://doi.org/10.1080/07391102.2020.1794974
  • Ramsay, R. R., Popovic-Nikolic, M. R., Nikolic, K., Uliassi, E., & Bolognesi, M. L. (2018). A perspective on multi-target drug discovery and design for complex diseases. Clinical and Translational Medicine, 7(1), 1–14. https://doi.org/10.1186/s40169-017-0181-2
  • Reymond, J.-L. (2015). The chemical space project. Accounts of Chemical Research, 48(3), 722–730. https://doi.org/10.1021/ar500432k
  • Salomon‐Ferrer, R., Case, D. A., & Walker, R. C. (2013). An overview of the Amber biomolecular simulation package. Wiley Interdisciplinary Reviews: Computational Molecular Science, 3(2), 198–210. https://doi.org/10.1002/wcms.1121
  • Santana, M. V., & Silva, F. P. Jr, (2021). De novo design and bioactivity prediction of SARS-CoV-2 main protease inhibitors using recurrent neural network-based transfer learning. BMC Chemistry, 15(1), 1–20. https://doi.org/10.1186/s13065-021-00737-2
  • Scannell, J. W., Blanckley, A., Boldon, H., & Warrington, B. (2012). Diagnosing the decline in pharmaceutical R&D efficiency. Nature Reviews. Drug Discovery, 11(3), 191–200. https://doi.org/10.1038/nrd3681
  • Schneider, G. (2018). Automating drug discovery. Nature Reviews. Drug Discovery, 17(2), 97–113. https://doi.org/10.1038/nrd.2017.232
  • Schneider, G., & Fechner, U. (2005). Computer-based de novo design of drug-like molecules. Nature Reviews. Drug Discovery, 4(8), 649–663. https://doi.org/10.1038/nrd1799
  • Schneider, P., & Schneider, G. (2016). De novo design at the edge of chaos: Miniperspective. Journal of Medicinal Chemistry, 59(9), 4077–4086. https://doi.org/10.1021/acs.jmedchem.5b01849
  • Smalley, K. S., Haass, N. K., Brafford, P. A., Lioni, M., Flaherty, K. T., & Herlyn, M. (2006). Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases. Molecular Cancer Therapeutics, 5(5), 1136–1144. https://doi.org/10.1158/1535-7163.MCT-06-0084
  • Stumpfe, D., Dimova, D., & Bajorath, J. R (2014). Composition and topology of activity cliff clusters formed by bioactive compounds. Journal of Chemical Information and Modeling, 54(2), 451–461. https://doi.org/10.1021/ci400728r
  • Tang, B., He, F., Liu, D., He, F., Wu, T., Fang, M., Niu, Z., Wu, Z., & Xu, D. (2022). AI-aided design of novel targeted covalent inhibitors against SARS-CoV-2. Biomolecules, 12(6), 746. https://doi.org/10.3390/biom12060746
  • Tiwari, V. (2021). Denovo designing, retro-combinatorial synthesis, and molecular dynamics analysis identify novel antiviral VTRM1. 1 against RNA-dependent RNA polymerase of SARS CoV2 virus. International Journal of Biological Macromolecules, 171, 358–365. https://doi.org/10.1016/j.ijbiomac.2020.12.223
  • Ton, A. T., Gentile, F., Hsing, M., Ban, F., & Cherkasov, A. (2020). Rapid identification of potential inhibitors of SARS‐CoV‐2 main protease by deep docking of 1.3 billion compounds. Molecular Informatics, 39(8), 2000028. https://doi.org/10.1002/minf.202000028
  • Torjesen, I. (2015). Drug development: The journey of a medicine from lab to shelf. Pharmaceutical Journal,.
  • Torrey, L., & Shavlik, J. (2009). Transfer learning. Handbook of research on machine learning applications. IGI Global.
  • Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334
  • Tyagi, R., Paul, A., Raj, V. S., Ojha, K. K., Kumar, S., Panda, A. K., Chaurasia, A., & Yadav, M. K. (2023). A drug repurposing approach to identify therapeutics by screening pathogen box exploiting SARS‐CoV‐2 main protease. Chemistry & Biodiversity, 20(2), e202200600. https://doi.org/10.1002/cbdv.202200600
  • Ullrich, S., & Nitsche, C. (2020). The SARS-CoV-2 main protease as drug target. Bioorganic & Medicinal Chemistry Letters, 30(17), 127377. https://doi.org/10.1016/j.bmcl.2020.127377
  • Wang, Y., Khan, A., Chandra Kaushik, A., Junaid, M., Zhang, X., & Wei, D.-Q. (2019). The systematic modeling studies and free energy calculations of the phenazine compounds as anti-tuberculosis agents. Journal of Biomolecular Structure & Dynamics, 37(15), 4051–4069. https://doi.org/10.1080/07391102.2018.1537896
  • Weininger, D. (1988). SMILES, a chemical language and information system. 1. Introduction to methodology and encoding rules. Journal of Chemical Information and Computer Sciences, 28(1), 31–36. https://doi.org/10.1021/ci00057a005

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