Promising inhibitors against main protease of SARS CoV-2 from medicinal plants: In silico identification

EBENEZER, OLUWAKEMI; SHAPI, MICHAEL

doi:10.2478/acph-2022-0020

Abstract

Some compounds reported as active against SARS CoV were selected, and docking studies were performed using the main protease of SARS CoV-2 as the receptor. The docked complex analysis shows that the ligands selectively bind with the target residues and binding affinity of amentoflavone (–10.1 kcal mol^–1), isotheaflavin-3’-gallate (–9.8 kcal mol^–1), tomentin A and D (–8.0 and –8.8 kcal mol^–1), theaflavin-3,3’-digallate (–8.6 kcal mol^–1), papyriflavonol A (–8.4 kcal mol^–1), iguesterin (–8.0 kcal mol^–1) and savinin (–8.3 kcal mol^–1) were ranked above the binding affinity of the reference, co-crystal ligand, ML188, a furan-2-carboxamide-based compound. To pinpoint the drug-like compound among the top-ranked compounds, the Lipinski’s rule of five and pharmacokinetic properties of all the selected compounds were evaluated. The results detailed that savinin exhibits high gastrointestinal absorption and can penetrate through the blood-brain barrier. Also, modifying these natural scaffolds with excellent binding affinity may lead to discovering of anti-SARS CoV agents with promising safety profiles.

References

A. Rahimi, A. Mirzazadeh and S. Tavakolpour, Genetics and genomics of SARS CoV-2: A review of the literature with the special focus on genetic diversity and SARS CoV-2 genome detection, Genomics 113 (2021) 1221–1232; https://doi.org/10.1016/j.ygeno.2020.09.05910.1016/j.ygeno.2020.09.059752524333007398
Search in Google Scholar Back to article
Y. A. Helmy, M. Fawzy, A. Elaswad, A. Sobieh, S. P. Kenney and A. A. Shehata, The COVID-19 pandemic: A comprehensive review of taxonomy, genetics, epidemiology, diagnosis, treatment, and control, J. Clin. Med. 9 (2020) Article ID 1225; https://doi.org/10.3390/jcm904122510.3390/jcm9041225723057832344679
Search in Google Scholar Back to article
D. E. Gordon, G. M. Jang, M. Bouhaddou, J. Xu, K. Obernier, K. M. White, M. J. O’Meara, V. V. Rezelj, J. Z. Guo, D. L. Swaney, T. A. Tummino, R. Hüttenhain, R. M. Kaake, A. L. Richards, B. Tutuncuoglu, H. Foussard, J. Batra, K. Haas, M. Modak, M. Kim, P. Haas, B. J. Polacco, H. Braberg, J. M. Fabius, M. Eckhardt, M. Soucheray, M. J. Bennett, M. Cakir, M. J. McGregor, Q. Li, B. Meyer, F. Roesch, T. Vallet, A. Mac Kain, L. Miorin, E. Moreno, Z. Z. Chi Naing, Y. Zhou, S. Peng, Y. Shi, Z. Zhang, W. Shen, I. T. Kirby, J. E. Melnyk, J. S. Chorba, K. Lou, S. A. Dai, I. Barrio-Hernandez, D. Memon, C. Hernandez-Armenta, J. Lyu, C. J. P. Mathy, T. Perica, K. B. Pilla, S. J. Ganesan, D. J. Saltzberg, R. Rakesh, X. Liu, S. B. Rosenthal, L. Calviello, S. Venkataramanan, J. Liboy-Lugo, Y. Lin, X.-P. Huang, Y. F. Liu, S. A. Wankowicz, M. Bohn, M. Safari, F. S. Ugur, C. Koh, N. S. Savar, Q. D. Tran, D. Shengjuler, S. J. Fletcher, M. C. O’Neal, Y. Cai, J. C. J. Chang, D. J. Broadhurst, S. Klippsten, P. P. Sharp, N. A. Wenzell, D. Kuzuoglu-Ozturk, H.-Y. Wang, R. Trenker, J. M. Young, D. A. Cavero, J. Hiatt, T. L. Roth, U. Rathore, A. Subramanian, J. Noack, M. Hubert, R. M. Stroud, A. D. Frankel, O. S. Rosenberg, K. A. Verba, D. A. Agard, M. Ott, M. Emerman, N. Jura, M. von Zastrow, E. Verdin, A. Ashworth, O. Schwartz, C. d’Enfert, S. Mukherjee, M. Jacobson, H. S. Malik, D. G. Fujimori, T. Ideker, C. S. Craik, S. N. Floor, J. S. Fraser, J. D. Gross, A. Sali, B. L. Roth, D. Ruggero, J. Taunton, T. Kortemme, P. Beltrao, M. Vignuzzi, A. García-Sastre, K. M. Shokat, B. K. Shoichet, N. J. Krogan, A SARS-CoV-2 protein interaction map reveals targets for drug repurposing, Nature 583 (2020) 459–468; https://doi.org/10.1038/s41586-020-2286-910.1038/s41586-020-2286-9743103032353859
Search in Google Scholar Back to article
J.-S. Kim, J. Jang, J. Kim, Y. Chung, C. Yoo and M. Han, Genome-wide identification and characterization of point mutations in the SARS CoV-2 genome, Osong Public Health Res. Perspect. 11 (2020) 101–111; https://doi.org/10.24171/j.phrp.2020.11.310.24171/j.phrp.2020.11.3.05
Search in Google Scholar Back to article
M. Rastogi, N. Pandey, A. Shukla and S. K. Singh, SARS coronavirus 2:From genome to infectome, Respir. Res. 21 (2020) Article ID 318; https://doi.org/10.1186/s12931-020-01581-z10.1186/s12931-020-01581-z770617533261606
Search in Google Scholar Back to article
Q. Li, X. Guan, P. Wu, X. Wang, L. Zhou, Y. Tong, R. Ren, K. Leung, E. Lau, J. Wong, X. Xing, N. Xiang, Y. Wu, C. Li, Q. Chen, D. Li, T. Liu, J. Zhao, M. Liu, W. Tu and Z. Feng, Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia, N. Engl. J. Med. 382 (2020) 1199–1207; https://doi.org/10.1056/NEJMoa200131610.1056/NEJMoa2001316712148431995857
Search in Google Scholar Back to article
COVID-19 Vaccine & Therapeutics Tracker; https://biorender.com/covid-vaccine-tracker; last access date August 5, 2021
Search in Google Scholar Back to article
A. N. M. Alamgir, Pharmacognostical Botany: Classification of Medicinal and Aromatic Plants (Maps), in Pharmacognostical Botany, Botanical Taxonomy, Morphology, and Anatomy of Drug Plants, in Therapeutic Use of Medicinal Plants and Their Extracts, Vol. 1, Springer International Publishing AG, Cham (Switzerland), 2017, pp. 177–293.10.1007/978-3-319-63862-1_6
Search in Google Scholar Back to article
O. Ebenezer, M. A. Jordaan, N. Damoyi and M. Shapi, Discovery of potential inhibitors for RNA-dependent RNA polymerase of norovirus: Virtual screening, and molecular dynamics, Int. J. Mol. Sci. 22 (2021) Article ID 171 (24 pages); https://doi.org/10.3390/ijms2201017110.3390/ijms22010171779572733375298
Search in Google Scholar Back to article
O. Ebenezer, O. Bodede, P. Awolade, M. A. Jordaan, R. E. Ogunsakin and M. Shapi, Medicinal plants with anti-SARS-CoV activity repurposing for treatment of COVID-19 infection: A systematic review and meta-analysis, Acta Pharm. 72 (2022) 199–224; https://doi.org/10.2478/acph-2022-002110.2478/acph-2022-0021
Search in Google Scholar Back to article
Y. H. Song, D. W. Kim, M. J. Curtis-Long, H. J. Yuk, Y. Wang, N. Zhuang, K. H. Lee, K. S. Jeon and K. H. Park, Papain-like protease (PLpro) inhibitory effects of cinnamic amides from Tribulus terrestris fruits, Biol. Pharm. Bull. 37 (2014) 1021–1028; https://doi.org/10.1248/bpb.b14-0002610.1248/bpb.b14-0002624882413
Search in Google Scholar Back to article
C.-W. Lin, F.-J. Tsai, C.-H. Tsai, C.-C. Lai, L. Wan, T.-Y. Ho, C.-C. Hsieh and P.-D. L. Chao, Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds, Antiviral Res. 68 (2005) 36–42; https://doi.org/10.1016/j.antiviral.2005.07.00210.1016/j.antiviral.2005.07.002711432116115693
Search in Google Scholar Back to article
Y. Park, H. Kim, M. Kim, J. Jeong, W. Kim, H. Park, J. Kwon, J. Park, S. Lee and B Ryu, Tanshinones as selective and slow-binding inhibitorsFor SARS CoV cysteine proteases, Bioorg. Med. Chem. 20 (2012) 5928–5935; https://doi.org/10.1016/j.bmc.2012.07.0310.1016/j.bmc.2012.07.038
Search in Google Scholar Back to article
Y. Park, H. Kim, M. Kim, J. Jeong, W. Kim, H. Park, J. Kwon, J. Park, S. Lee and B. Ryu, Chalcones isolated from Angelica keiskei inhibit cysteine proteases of SARS CoV, J. Enzyme Inhib. Med. Chem. 31 (2016) 23–30; https://doi.org/10.3109/14756366.2014.100321510.3109/14756366.2014.100321525683083
Search in Google Scholar Back to article
S. Jo, S. Kim, H. Shin and S. Kim, Inhibition of SARS CoV 3CL protease byFlavonoids, J. Enzyme Inhib. Med. Chem. 35 (2020) 145–151; https://doi.org/10.1080/14756366.2019.169048010.1080/14756366.2019.1690480688243431724441
Search in Google Scholar Back to article
B. Ryu, H. Jeong, H. Kim, M. Kim, Y. Park, D. Kim, T. Nguyen, J. Park, S. Chang, H. Park, C. Rho and S. Lee, Biflavonoids from Torreya nucifera displaying SARS CoV 3CL(pro) inhibition, Bioorg. Med. Chem. 18 (2010) 7940–7947; https://doi.org/10.1016/j.bmc.2010.09.0351710.1016/j.bmc.2010.09.035
Search in Google Scholar Back to article
W. Kim, H. Seo, J. Curtis-Long, Y. Oh, W. Oh, K. Cho, H. Lee and H. Park, Phenolic phytochemical displaying SARS CoV papain-like protease inhibition from the seeds of Psoralea corylifolia, J. Enzyme Inhib. Med. Chem. 29 (2014) 59–63; https://doi.org/10.3109/14756366.2012.7535911810.3109/14756366.2012.753591
Search in Google Scholar Back to article
J.-Y. Park, H. J. Jeong, J. H. Kim, Y. M. Kim, S.-J. Park, D. Kim, K. H. Park, W. S. Lee and Y. B. Ryu, Diarylheptanoids from Alnus japonica inhibit papain-like protease of severe acute respiratory syndrome coronavirus, Biol. Pharm. Bull. 35 (2012) 2036–2042; https://doi.org/10.1248/bpb.b12-0062310.1248/bpb.b12-0062322971649
Search in Google Scholar Back to article
B. Ryu, J. Park, M. Kim, Y. Lee, D. Seo, S. Chang, H. Park, C. Rhoand and S. Lee, SARS CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii, Bioorg. Med. Chem. Lett. 20 (2010) 1873–1876; https://doi.org/10.1016/j.bmcl.2010.01.1522010.1016/j.bmcl.2010.01.152
Search in Google Scholar Back to article
N. Chen, P. Lin, K. Huang, C. Chen, P. Hsieh, H. Liang and T. Hsu, Inhibition of SARS CoV 3C-like protease activity by theaflavin-3,3’-digallate (TF3), Evid. Based Complement. Alternat. Med. 2 (2005) 209–215; https://doi.org/10.1093/ecam/neh08110.1093/ecam/neh081114219315937562
Search in Google Scholar Back to article
J. Cho, J. Curtis-Long, H. Lee, D. Kim, W. Ryu, J. Yuk and H. Park, Geranylated Flavonoids displaying SARS CoV papain-like protease inhibition from the fruits of Paulownia tomentosa, Bioorg. Med. Chem. 21 (2013) 3051–3057; https://doi.org/10.1016/j.bmc.2013.03.0272210.1016/j.bmc.2013.03.027
Search in Google Scholar Back to article
C.-C. Wen, Y.-H. Kuo, J.-T. Jan, P.-H. Liang, S.-Y. Wang, H.-G. Liu, C.-K. Lee, S.-T. Chang, C.-J. Kuo, S.-S. Lee, C.-C. Hou, P.-W. Hsiao, S.-C. Chien, L.-F. Shyur and N. S. Yang, Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus, J. Med. Chem. 50 (2007) 4087–4095; https://doi.org/10.1021/jm070295s10.1021/jm070295s17663539
Search in Google Scholar Back to article
Z. Jin, X. Du, Y. Xu, Y. Deng, M. Liu, Y. Zhao, B. Zhang, X. Li, L. Zhang, C. Peng, Y. Duan, J. Yu, L. Wang, K. Yang, F. Liu, R. Jiang, X. Yang, T. You, X. Liu, X. Yang, F. Bai, H. Liu, X. Liu, L. W. Guddat, W. Xu, G. Xiao, C. Qin, Z. Shi, H. Jiang, Z. Rao and H. Yang, Structure of MproFrom SARS-CoV-2 and discovery of its inhibitors, Nature 582 (2020) 289–293; https://doi.org/10.1038/s41586-020-2223-y10.1038/s41586-020-2223-y32272481
Search in Google Scholar Back to article
A. Jordaan, O. Ebenezer, N. Damoyi and M. Shapi, Virtual screening, molecular docking studies and DFT calculations of FDA approved compounds similar to the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz, Heliyon 6 (2020) e04642; https://doi.org/10.1016/j.heliyon.2020.e046422510.1016/j.heliyon.2020.e04642
Search in Google Scholar Back to article
O. Trott and J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoringFunction, efficient optimization, and multithreading, J. Comput. Chem. 31 (2010) 455–461; https://doi.org/10.1002/jcc.2133410.1002/jcc.21334304164119499576
Search in Google Scholar Back to article
A. Daina, O. Michielin and V. Zoete, SwissADME: aFree web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistryFriendliness of small molecules, Sci. Rep. 7 (2017) Article ID 42717; https://doi.org/10.1038/srep4271710.1038/srep42717533560028256516
Search in Google Scholar Back to article

Promising inhibitors against main protease of SARS CoV-2 from medicinal plants: In silico identification

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