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In Silico Evaluation of Promising Naturally Occurring Bioactive Ligands Against Molecular Targets of SARS-Cov-2

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Abstract

The fatal virus SARS-CoV-2 emerged in December 2019, which caused a global pandemic of coronavirus disease, also known as COVID-19. Identification of the naturally occurring bioactive compounds that can inhibit or modulate the proteins and enzymes of the virus SARS-CoV-2 by targeting the host cells and immune system of the human body is an instrumental approach for COVID-19 therapy. It is an attempt to assess the potential of naturally occurring bioactive compounds and their derivatives against coronavirus using molecular docking and molecular dynamics simulation studies, i.e. binding affinity of the active receptors of the host cells to the selected bioactive compound against SARS-CoV-2. Docking and MD simulation studies were carried out in this study to estimate the affinity of the selected bioactive compounds along with the reference drugs remdesivir and ivermectin in opposition to the vital target proteins and enzymes of coronavirus. Among all selected bioactives, as per the computational docking parameters, curcumin has shown excellent binding, especially against ACE-2 and RdRp. Apigenin also showed encouraging results against spike protein comparable to reference drugs remdesivir and ivermectin. These results are furthermore established by the molecular dynamic simulation study and analysis of protein–ligand complex, which shows minimum binding deviation and minor average fluctuations in energies of protein residues throughout the simulation period. Curcumin glucuronide and apigenin 7-glucoside showed the most suitable response as they have a marvellous binding affinity with COVID-19 targets that are responsible for viral entry as well as their further replication into the host cell; hence, they could be some possible potential drug candidates for COVID-19 therapy.

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References

  1. Sachs JD, Horton R, Bagenal J et al (2020) The Lancet COVID-19 Commission. Lancet 396:454–455. https://doi.org/10.1016/S0140-6736(20)31494-X

    Article  PubMed  PubMed Central  Google Scholar 

  2. Zhou Y, Hou Y, Shen J et al (2020) Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov 6:14. https://doi.org/10.1038/s41421-020-0153-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Eweas AF, Alhossary AA, Abdel-Moneim AS (2020) Molecular docking reveals ivermectin and remdesivir as potential repurposed drugs against SARS-CoV-2. Front Microbiol 11:592908. https://doi.org/10.3389/fmicb.2020.592908

    Article  PubMed  Google Scholar 

  4. Bajorath J (2002) Integration of virtual and high-throughput screening. Nat Rev Drug Discov 1:882–894. https://doi.org/10.1038/nrd941

    Article  CAS  PubMed  Google Scholar 

  5. Soni U, Singh P, Gupta OP et al (2022) Lichen planus drugs re-purposing as potential anti COVID-19 therapeutics through molecular docking and molecular dynamics simulation approach. J Clin Transl Res 8:127–146. https://doi.org/10.18053/jctres.08.202202.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mollica V, Rizzo A, Massari F (2020) The pivotal role of TMPRSS2 in coronavirus disease 2019 and prostate cancer. Future Oncol 16:2029–2033. https://doi.org/10.2217/fon-2020-0571

    Article  CAS  PubMed  Google Scholar 

  7. Gao Y, Yan L, Huang Y et al (2020) Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science 368:779–782. https://doi.org/10.1126/science.abb7498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kim K-J, Liu X, Komabayashi T et al (2016) Natural products for infectious diseases. Evid Based Complement Altern Med 2016:9459047. https://doi.org/10.1155/2016/9459047

    Article  Google Scholar 

  9. Chakraborty C, Sharma AR, Mallick B et al (2021) Evaluation of molecular interaction, physicochemical parameters and conserved pattern of SARS-CoV-2 Spike RBD and hACE2: in silico and molecular dynamics approach. Eur Rev Med Pharmacol Sci 25:1708–1723. https://doi.org/10.26355/eurrev_202102_24881

    Article  CAS  PubMed  Google Scholar 

  10. Almeida-Neto FWQ, Castro Matos MG, Marinho EM et al (2021) In silico study of the potential interactions of 4’-acetamidechalcones with protein targets in SARS-CoV-2. Biochem Biophys Res Commun 537:71–77. https://doi.org/10.1016/j.bbrc.2020.12.074

    Article  CAS  Google Scholar 

  11. Parihar A, Sonia ZF, Akter F et al (2022) Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: a promising therapeutic approach for Tackling COVID-19. Comput Biol Med 145:105468. https://doi.org/10.1016/j.compbiomed.2022.105468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang S, Fang X, Wang Y (2022) In silico screening of novel TMPRSS2 inhibitors for treatment of COVID-19. Molecules 27:4210. https://doi.org/10.3390/molecules27134210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Domínguez-Villa FX, Durán-Iturbide NA, Ávila-Zárraga JG (2021) Synthesis, molecular docking, and in silico ADME/Tox profiling studies of new 1-aryl-5-(3-azidopropyl)indol-4-ones: potential inhibitors of SARS CoV-2 main protease. Bioorg Chem 106:104497. https://doi.org/10.1016/j.bioorg.2020.104497

    Article  CAS  PubMed  Google Scholar 

  14. Hostetler GL, Ralston RA, Schwartz SJ (2017) Flavones: food sources, bioavailability, metabolism, and bioactivity. Adv Nutr 8:423–435. https://doi.org/10.3945/an.116.012948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pandareesh MD, Shrivash MK, Naveen Kumar HN et al (2016) Curcumin monoglucoside shows improved bioavailability and mitigates rotenone induced neurotoxicity in cell and Drosophila models of Parkinson’s disease. Neurochem Res 41:3113–3128. https://doi.org/10.1007/s11064-016-2034-6

    Article  CAS  PubMed  Google Scholar 

  16. Maurya VK, Kumar S, Prasad AK et al (2020) Structure-based drug designing for potential antiviral activity of selected natural products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor. Virusdisease 31:179–193. https://doi.org/10.1007/s13337-020-00598-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fidelis QC, Faraone I, Russo D et al (2019) Chemical and biological insights of Ouratea hexasperma (A. St.-Hil.) Baill.: a source of bioactive compounds with multifunctional properties. Nat Prod Res 33:1500–1503. https://doi.org/10.1080/14786419.2017.1419227

    Article  CAS  PubMed  Google Scholar 

  18. Salehi B, Venditti A, Sharifi-Rad M et al (2019) The therapeutic potential of apigenin. Int J Mol Sci 20:1305. https://doi.org/10.3390/ijms20061305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Villa-Rodriguez JA, Kerimi A, Abranko L et al (2018) Acute metabolic actions of the major polyphenols in chamomile: an in vitro mechanistic study on their potential to attenuate postprandial hyperglycaemia. Sci Rep 8:5471. https://doi.org/10.1038/s41598-018-23736-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lim R, Barker G, Wall CA, Lappas M (2013) Dietary phytophenols curcumin, naringenin and apigenin reduce infection-induced inflammatory and contractile pathways in human placenta, foetal membranes and myometrium. Mol Hum Reprod 19:451–462. https://doi.org/10.1093/molehr/gat015

    Article  CAS  PubMed  Google Scholar 

  21. Sharma RA, Steward WP, Gescher AJ (2007) Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med Biol 595:453–470. https://doi.org/10.1007/978-0-387-46401-5_20

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors are thankful to the department of Applied Sciences, the Indian Institute of Information Technology, Allahabad, for providing us with the facilities and encouragement.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Applied Sciences, Indian Institute of Information Technology, Allahabad, Prayagraj, Uttar Pradesh, India

    Unnati Soni & Krishna Misra

  2. Agro Processing Technology Division, CSIR- National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India

    Tripti Mishra

  3. Department of General Surgery, Career Institute of Medical Sciences, Lucknow, India

    O. P. Gupta

  4. Phytochemistry Division, CSIR-National Botanical Research Institute, Lucknow, India

    Mahesh Pal

  5. Department of Oral Pathology and Microbiology, King George’s Medical University, Lucknow, Uttar Pradesh, 226003, India

    Shalini Gupta, Saurabh Pratap Singh & Amita Sangwan

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Correspondence to Shalini Gupta.

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Significance statement: The fatal SARS-CoV-2 emerged in December 2019, which caused a global pandemic of coronavirus disease, also known as COVID-19. Identifying the naturally occurring bioactive compounds that can inhibit or modulate the proteins and enzymes of the virus SARS-CoV-2 by targeting the human body's host cells and the immune system is an instrumental approach for COVID-19 therapy. It is an effort to assess the potential of naturally occurring bioactive compounds and their derivatives against SARS-CoV-2 using molecular docking and molecular dynamics simulation studies. Curcumin has shown excellent binding among all selected bioactive as per the computational docking parameters, especially against ACE-2 and RdRp. Apigenin also showed encouraging results against spike protein comparable to reference drugs remdesivir and ivermectin. These results are confirmed by the molecular dynamics simulation study and analysis of the protein–ligand complex, which shows minimum binding deviation and minor average fluctuations in the energies of protein residues throughout the simulation period. Curcumin glucuronide and apigenin 7-glucoside showed the most suitable response as they have a marvellous binding affinity with SARS-CoV-2 targets responsible for viral entry and their further replication into the host cell; hence, they could be some possible potential drug candidates for COVID-19 therapy.

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Soni, U., Mishra, T., Gupta, O.P. et al. In Silico Evaluation of Promising Naturally Occurring Bioactive Ligands Against Molecular Targets of SARS-Cov-2. Proc. Natl. Acad. Sci., India, Sect. B Biol. Sci. 94, 251–260 (2024). https://doi.org/10.1007/s40011-023-01496-x

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