Effectiveness of Quercetin and Its Derivatives Against SARS CoV2 -In silico Approach

Authors

  • M Harish SCMS School of Technology and Management, Biotechnology Division -SIBB R&D, S. Kalamassery, Kochi, Kerala, India-682033
  • C V Ranjith SCMS School of Technology and Management, Biotechnology Division -SIBB R&D, S. Kalamassery, Kochi, Kerala, India-682033
  • C Sethulekshmy Nair SCMS School of Technology and Management, Biotechnology Division -SIBB R&D, S. Kalamassery, Kochi, Kerala, India-682033

DOI:

https://doi.org/10.18006/2022.10(5).1003.1015

Keywords:

SARS CoV2, Antivirals, Phytochemical, Binding studies, Quercetin derivatives

Abstract

The COVID-19 pandemic that erupted in November 2019 is continuing, with no effective antiviral agent to date. Synthetic antiviral agents have limitations such as a narrow range of therapeutic effectiveness of the activity, toxicity, and resistant viral strains and traditional antiviral medicines at large seem not to have these limitations. Here, some of the existing phytochemicals are cherry-picked for repurposing against the enzyme or protein targets of SARS CoV2, by the principles of structure-based drug design based on molecular docking studies. The most important drug targets of SARS CoV2 namely, Mpro protease (6LU7), RdRp polymerase (7BTF), and Spike glycoprotein of SARS CoV2(6VSB) were employed for docking analysis with chosen phytochemicals and binding affinity was calculated using PRODIGY software and docking sites determined using Chimera software. For docking studies, 160 phytochemicals were selected from a large pool of phytochemicals. Based on the binding affinity values, 61 phytoconstituents were selected for further in-silico screening which resulted in 15 phytochemicals, with higher binding affinity to spike glycoprotein of SARS CoV2. Moreover, Guaijaverin, Quercetin, Quercitrin, Quinic acid, and spiraeoside binds both to the spike glycoprotein of SARS Cov2 and the host receptor of human ACE2. Hence these compounds may serve as two-pronged drug candidates for SARS CoV2. In nutshell, we present a few phytochemical candidates with higher binding affinity to the Spike protein of SARS CoV2, which needs to be further optimized by in vitro studies to minimize the cytotoxicity and increase or retain the binding affinity, towards an effective antiviral drug against COVID 19.

References

Ambrose, J. M., Kullappan, M., Patil, S., Alzahrani, K. J., et al. (2022). Plant-Derived Antiviral Compounds as Potential Entry Inhibitors against Spike Protein of SARS-CoV-2 Wild-Type and Delta Variant: An Integrative in SilicoApproach. Molecules (Basel, Switzerland), 27(6), 1773. 1-26. DOI: https://doi.org/10.3390/molecules27061773

Bachar, S. C., Mazumder, K., Bachar, R., Aktar, A., & Al Mahtab, M. (2021). A Review of Medicinal Plants with Antiviral Activity Available in Bangladesh and Mechanistic Insight In to Their Bioactive Metabolites on SARS-CoV-2, HIV and HBV. Frontiers in pharmacology, 12, 732891. DOI: https://doi.org/10.3389/fphar.2021.732891

Banerjee, P., Eckert, A.O., Schrey, A.K., &Preissner, R. (2018). ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic acids research, 46(W1), W257-63. DOI: https://doi.org/10.1093/nar/gky318

Cagliani, R., Forni, D., Clerici, M., & Sironi, M. (2020). Computational inference of selection underlying the evolution of the novel coronavirus, SARS-CoV-2. Journal of Virology, 16(10), 1678–1685. DOI: https://doi.org/10.1128/JVI.00411-20

Chatterjee, P., Nagi, N., Agarwal, A., Das, B., Banerjee, S., Sarkar, S., & Gangakhedkar, R. R. (2020). The 2019 novel coronavirus disease (COVID-19) pandemic: A review of the current evidence. The Indian journal of medical research, 151(2-3), 147–159. DOI: https://doi.org/10.4103/ijmr.IJMR_519_20

Chiu, N. C., Chi, H., Tai, Y. L., Peng, C. C., et al. (2020). Impact of wearing masks, hand hygiene, and social distancing on influenza, enterovirus, and all-cause pneumonia during the coronavirus pandemic: retrospective national epidemiological surveillance study. Journal of medical Internet research, 22(8), e21257. DOI: https://doi.org/10.2196/21257

Daina, A., Michielin, O., & Zoete, V. (2017). Swiss ADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific reports, 7, 42717 DOI: https://doi.org/10.1038/srep42717

Dhama, K., Sharun, K., Tiwari, R., Dadar, M., Malik, Y. S., Singh, K. P., & Chaicumpa, W. (2020). COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics. Human Vaccines & Immunotherapeutics, 16(6): 1232–1238. DOI: https://doi.org/10.1080/21645515.2020.1735227

Domitrović, R., & Potočnjak, I. (2016). A comprehensive overview of hepatoprotective natural compounds: mechanism of action and clinical perspectives. Archives of Toxicology, 90(1), 39-79. DOI: https://doi.org/10.1007/s00204-015-1580-z

Fahmi, M., Kubota, Y., & Ito, M. (2020). Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV. Infection, Genetics and Evolution, 81, 104272. DOI: https://doi.org/10.1016/j.meegid.2020.104272

Hussain, M., Jabeen, N., Amanullah, A., Baig, A. A., Aziz, B., Shabbir, S., Raza, F., & Uddin, N. (2020). Molecular docking between human TMPRSS2 and SARS-CoV-2 spike protein: conformation and intermolecular interactions. AIMS microbiology, 6(3), 350–360. DOI: https://doi.org/10.3934/microbiol.2020021

Idrees, M., Khan, S., Memon, N. H., & Zhang, Z. (2021). Effect of the Phytochemical Agents against the SARS-CoV and Some of them Selected for Application to COVID-19: A Mini-Review. Current Pharmaceutical Biotechnology, 22(4), 444-450. DOI: https://doi.org/10.2174/1389201021666200703201458

Letko, M., Marzi, A., & Munster, V. (2020). Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nature microbiology, 5(4), 562-569 DOI: https://doi.org/10.1038/s41564-020-0688-y

Lin, L.T., Hsu, W.C., & Lin, C.C. (2014) Antiviral natural products and herbal medicines. Journal of Traditional and Complementary Medicine, 4(1), 24-35. DOI: https://doi.org/10.4103/2225-4110.124335

Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., & Bi, Y. (2020). Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet, 395(10224), 565-574. DOI: https://doi.org/10.1016/S0140-6736(20)30251-8

Luan, J., Lu, Y., Jin, X., & Zhang, L. (2020). Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection. Biochemical and biophysical research communications, 526(1):165-169. DOI: https://doi.org/10.1016/j.bbrc.2020.03.047

Luk, H. K., Li, X., Fung, J., Lau, S. K., & Woo, P. C. (2019). Molecular epidemiology, evolution and phylogeny of SARS coronavirus. Infection, Genetics and Evolution, 71, 21–30. DOI: https://doi.org/10.1016/j.meegid.2019.03.001

Ma, L. L., Ge, M., Wang, H. Q., Yin, J. Q., Jiang, J. D., & Li, Y. H. (2015). Antiviral activities of several oral traditional Chinese medicines against influenza viruses. Evidence-Based Complementary and Alternative Medicine, 2015, 367250. https://doi.org/10.1155/2015/367250. DOI: https://doi.org/10.1155/2015/367250

Mukhtar, M., Arshad, M., Ahmad, M., Pomerantz, R. J., Wigdahl, B., & Parveen, Z. (2008). Antiviral potentials of medicinal plants. Virus research, 131(2), 111-120. DOI: https://doi.org/10.1016/j.virusres.2007.09.008

O'Boyle, N. M., Banck, M., James, C. A., Morley, C., Vandermeersch, T., & Hutchison, G. R. (2011). Open Babel: An open chemical toolbox. Journal of cheminformatics, 3(1), 1-14. DOI: https://doi.org/10.1186/1758-2946-3-33

Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004). UCSF Chimera—a visualization system for exploratory research and analysis. Journal of computational chemistry, 25(13), 1605-1612. DOI: https://doi.org/10.1002/jcc.20084

Pushpa, R., Nishant, R., Navin, K., & Pankaj, G. (2013). Antiviral Potential of Medicinal Plants- An Overview. International Research Journal of Pharmacy, 4 (6), 8-16 DOI: https://doi.org/10.7897/2230-8407.04603

Romano, M., Ruggiero, A., Squeglia, F., Maga, G., & Berisio, R. (2020). A Structural View of SARS-CoV-2 RNA Replication Machinery: RNA Synthesis, Proofreading and Final Capping. Cells, 9(5):1267. DOI: https://doi.org/10.3390/cells9051267

Sharma, A., Goyal, S., Yadav, A. K., Kumar, P., & Gupta, L. (2022). In-silico screening of plant-derived antivirals against main protease, 3CLpro and endoribonuclease, NSP15 proteins of SARS-CoV-2. Journal of biomolecular structure & dynamics, 40(1), 86–100. DOI: https://doi.org/10.1080/07391102.2020.1808077

Sharma, A., Tiwari, S., Deb, M.K., & Marty, J.L. (2020). Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): a global pandemic and treatment strategies. International Journal of Antimicrobial Agents, 56(2):106054. DOI: https://doi.org/10.1016/j.ijantimicag.2020.106054

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), 455–46. DOI: https://doi.org/10.1002/jcc.21334

V’kovski, P., Kratzel, A., Steiner, S., Stalder, H., & Thiel, V. (2021). Coronavirus biology and replication: implications for SARS-CoV-2. Nature Reviews Microbiology, 19(3), 155-70. DOI: https://doi.org/10.1038/s41579-020-00468-6

Vardhan, S., & Sahoo, S.K. (2020). In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19. Computers in biology and medicine, 124(103936), 1-12. DOI: https://doi.org/10.1016/j.compbiomed.2020.103936

Xue, L.C., Rodrigues, J.P., Kastritis, P.L., Bonvin, A.M., & Vangone, A. (2016). PRODIGY: a web server for predicting the binding affinity of protein–protein complexes. Bioinformatics, 32(23), 3676-8. DOI: https://doi.org/10.1093/bioinformatics/btw514

Yuan, M., Wu, N.C., Zhu, X., Lee, C.C., et al. (2020). A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV. Science, 368(6491):630-633. DOI: https://doi.org/10.1126/science.abb7269

Zheng, J. (2020). SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat. International Journal of Biological Sciences, 16(10), 1678. DOI: https://doi.org/10.7150/ijbs.45053

Downloads

Published

2022-10-31

How to Cite

Harish , M., Ranjith , C. V., & Nair, C. S. (2022). Effectiveness of Quercetin and Its Derivatives Against SARS CoV2 -In silico Approach. Journal of Experimental Biology and Agricultural Sciences, 10(5), 1003–1015. https://doi.org/10.18006/2022.10(5).1003.1015

Issue

Section

RESEARCH ARTICLES

Categories