A molecular docking study of SARS-CoV-2 main protease against phytochemicals of Boerhavia diffusa Linn. for novel COVID-19 drug discovery

VirusDisease - Tập 32 - Trang 46-54 - 2021
U. Rutwick Surya1, N. Praveen1
1Department of Life Sciences, CHRIST (Deemed to be University), Bengaluru, India

Tóm tắt

SARS-CoV-2, the causative virus of the Corona virus disease that was first recorded in 2019 (COVID-19), has already affected over 110 million people across the world with no clear targeted drug therapy that can be efficiently administered to the wide spread victims. This study tries to discover a novel potential inhibitor to the main protease of the virus, by computer aided drug discovery where various major active phytochemicals of the plant Boerhavia diffusa Linn. namely 2-3-4 beta-Ecdysone, Bioquercetin, Biorobin, Boeravinone J, Boerhavisterol, kaempferol, Liriodendrin, quercetin and trans-caftaric acid were docked to SAR-CoV-2 Main Protease using Molecular docking server. The ligands that showed the least binding energy were Biorobin with  − 8.17 kcal/mol, Bioquercetin with  − 7.97 kcal/mol and Boerhavisterol with  − 6.77 kcal/mol. These binding energies were found to be favorable for an efficient docking and resultant inhibition of the viral main protease. The graphical illustrations and visualizations of the docking were obtained along with inhibition constant, intermolecular energy (total and degenerate), interaction surfaces and HB Plot for all the successfully docked conditions of all the 9 ligands mentioned. Additionally the druglikeness of the top 3 hits namely Bioquercetin, Biorobin and Boeravisterol were tested by ADME studies and Boeravisterol was found to be a suitable candidate obeying the Lipinsky’s rule. Since the main protease of SARS has been reported to possess structural similarity with the main protease of MERS, comparative docking of these ligands were also carried out on the MERS Mpro, however the binding energies for this target was found to be unfavorable for spontaneous binding. From these results, it was concluded that Boerhavia diffusa possess potential therapeutic properties against COVID-19.

Tài liệu tham khảo

Paray A, Hussain BA, Qadir A, Attar FA, Aziz F, Hasan FM. A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin. J Biomol Struct Dyn. 2020. https://doi.org/10.1080/07391102.2020.1754293.

Zhao R, Li X, Niu J, Yang P, Wu B, Wang H, Song W, Huang H, Zhu B, Bi N, Ma Y, Zhan X, Wang F, Hu L, Zhou T, Hu H, Zhou Z, Zhao W, Tan L, Lu W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet. 2020;395(10224):565–74.

Zhao F, Yu S, Chen B, Wang YM, Song W, Hu ZG, Tao Y, Tian ZW, Pei JH, Yuan YY, Zhang ML, Dai YL, Liu FH, Wang Y, Zheng QM, Xu JJ, Holmes L, Zhang EC, Wu YZ. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265–9.

Worldometers.info. (2020) COVID-19 coronavirus pandemic. [Online]

Zia SA, Ashraf K, Uddin S, Ul-Haq R, Khan Z. Identification of chymotrypsin-like protease inhibitors of SARS-CoV-2 via integrated computational approach. J Biomol Struct Dyn. 2020. https://doi.org/10.1080/07391102.2020.1751298.

Chen F, Tan C, Yang W, Yang K, Wang H. Structure of main protease from human coronavirus NL63: Insights for wide spectrum anti-coronavirus drug design. Sci Rep. 2016;6(1):1–12.

Al-Obaidi AD, Ahin AS, Yelekc AT, Elmezayen IK. Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes. J Biomol Struct Dyn. 2020. https://doi.org/10.1080/07391102.2020.1758791.

Poma S, Kolandaivel AB, Boopathi P. Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. J Biomol Struct Dyn. 2020. https://doi.org/10.1080/07391102.2020.1758788.

Wang X, Liu XJ. Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines. J Genet Genom. 2020;47(2):119–21.

Froeyen MU, Mirza M. Structural elucidation of SARS-CoV-2 vital proteins: computational methods reveal potential drug candidates against main protease. Nsp12 RNA-dependent RNA polymerase and Nsp13 helicase. J Pharm Anal. 2020;10:320–8.

Jha RJ, Amera RK, Jain G, Singh M, Pathak E, Singh A, Muthukumaran RP, Singh J, Khan AK. Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2’-O-ribosemethyltransferase. J Biomol Struct Dyn. 2020. https://doi.org/10.1080/07391102.2020.1753577.

Barrila U, Velazquez-Campoy J, Leavitt A, Freire SA, Bacha E. Identification of novel inhibitors of the SARS coronavirus main protease 3CLpro. Biochem. 2004;43(17):4906–12.

Sims TP, Leist AC, Schäfer SR, Won A, Brown J, Montgomery AJ, Hogg SA, Babusis A, Clarke D, Spahn MO, Bauer JE, Sellers L, Porter S, Feng D, Cihlar JY, Jordan T, Denison R, Baric MR, Sheahan RS. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV,". Nat Commun. 2020;11(1):222.

Lin D, Sun X, Curth U, Drosten C, Sauerhering L, Becker S, Rox K, Hilgenfeld R, Zhang L. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved a-ketoamide inhibitors. Science. 2020;368:409–12.

Rolain P, Lagier JM, Brouqui JC, Raoult P, Colson D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020;55(4):105932.

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;56(1):105949.

Cao M, Zhang R, Yang L, Liu X, Xu J, Shi M, Hu Z, Zhong Z, Xiao W, Wang G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269–71.

Vemula MK, Donde S, Gouda R, Behera G, Vadde L, Gupta R. In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel. J Biomol Struct Dyn. 2020. https://doi.org/10.1080/07391102.2020.1751300.

Belhassan I, El Khatabi A, Lakhlifi K, El Idrissi T, Bouachrine M, Aanouz M. Moroccan medicinal plants as inhibitors of COVID-19: computational investigations. J Biomol Struct Dyn. 2020. https://doi.org/10.1080/07391102.2020.1758790.

Jadhav HR. Antioxidant properties of Indian medicinal plants. Phytother Res. 2002;16(8):771–3.

Vijayakumar M, Pushpangadan P, Govindarajan R. Antioxidant approach to disease management and the role of ’Rasayana’ herbs of Ayurveda. J Ethnopharmacol. 2005;99(2):165–78.

Nair AM, Kamal KK, Saraf MN, Mungantiwar AA. Adaptogenic activity of aqueous extract of the roots of Boerhaavia diffusa Linn. Indian Drugs. 1997;34(4):184–9.

Nair AM, Shinde UA, Saraf MN, Muntgantiwar AA. Effect of stress on plasma and adrenal cortisol levels and immune responsiveness in rats: modulation by alkaloidal fraction of Boerhaavia diffusa. Fitoterapia. 1997;68(6):498–500.

Mustafa SS, Sumanth M. Antistress, adoptogenic and immunopotentiating activity roots of Boerhaavia diffusa in mice. Int J Pharmacol. 2007;3(5):416–20.

Saluja D, Chopra M, Srivastava R. (2005) Isolation and screening of anticancer metabolites from Boerhavia diffusa. Indian J Med Res. 2005;151(1):S19.

Sreeja S. An in vitro study on antiproliferative and antiestrogenic effects of Boerhaavia diffusa L. extracts. J Ethnopharmacol. 2009;126(2):221–5.

Lini CC, Kuttan G, Leyon PV. (2005) Inhibitory effect of Boerhaavia diffusa on experimental metastasis by B16F10 melanoma in C57BL/6 mice. Life Sci. 2005;76(2):1339–49.

Kuttan G, Manu KA. (2007) Effect of punarnavine, an alkaloid from Boerhaavia diffusa, on cell-mediated immune responses and TIMP-1 in B16F–10 metastatic melanoma-bearing mice. Immunopharmacol Immunotoxicol. 2007;29(3–4):569–86.

Pari L, Satheesh MA. Antioxidant effect of Boerhavia diffusa L. in tissues of alloxan induced diabetic rats. Indian J Exp Biol. 2004;42(10):989–92.

Orisakwe OE, Afonne OJ, Gamaniel KS, Vongtau OH, Obi E, Chude MA. Hypoglycaemic effect of the aqueous extract of Boerhavia diffusa leaves. Indian J Pharmacol. 2001;33(3):215–6.

Amarnath Satheesh M, Pari L. Antidiabetic effect of Boerhavia diffusa: effect on serum and tissue lipids in experimental diabetes. J Med Food. 2004;7(4):472–6.

Mudgal V. Studies on medicinal properties of Convolvulus pluricaulis and Boerhaavia diffusa. Planta Med. 1975;28(1):62–8.

Gracioso JS, Bighetti EJB, Germonsen Robineou L, Souza Brito ARM, Hiruma-Lima CA. The juice of fresh leaves of Boerhaavia diffusa L. (Nyctaginaceae) markedly reduces pain in mice. J Ethnopharmacol. 2000;71(1–2):267–74.

Asadulla S. Anti-inflammatory activities of Boerhavia diffusa roots in Albino rats. Arch Pharm Sci Res. 2010;2:267–70.

Nayak P, Thirunavoukkarasu M. A review of the plant Boerhaavia diffusa: its chemistry, pharmacology and therapeutical potential. J Phytopharmacology. 2016;5(2):83–92.

Aeri V, Gaur PK, Jachak SM, Mishra S. Phytochemical, therapeutic, and ethnopharmacological overview for a traditionally important herb: Boerhavia diffusa Linn. BioMed Res Int. 2014. https://doi.org/10.1155/2014/808302.

Srivastava A, Jachak SM, Bairwa K. Quantitative analysis of Boeravinones in the roots of Boerhaavia diffusa by UPLC/PDA. Phytochem Anal. 2014. https://doi.org/10.1002/pca.2509.

Noba K, Ba AT, Gaydou EM, Kornprobst JM, Miralles J. Chemotaxonomy in Nyctagynaceae family: sterols and fatty acids from the leaves of three Boerhaavia species. Biochem Syst Ecol. 1988;16(5):475–8.

Bikadi Z, Hazai E. Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock. J Cheminf. 2009;1(1):1–16.

Halgren Merck TA. Molecular force field. I. Basis, form, scope, parametrization, and performance of MMFF94. J Comput Chem. 1998;17(5–6):490–519.

Morris GM, Goodsell DS. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem. 1998;19(14):1639–62.

Solis FJ, Wets RJB. Minimization by random search techniques. Math Oper Res. 1981;6(1):19–30.

Palanisamy M, Palanisamy S, Subramanian A, Rathinavel STT. Phytochemical 6-Gingerol–A promising Drug of choice for COVID-19. Int J Adv Sci Eng. 2020;6(4):1482–9.

Shakya A, Prasad SK, Singh S, Gurav NS, Prasad RS, Gurav SS, Sinha SK. An in-silico evaluation of different Saikosaponins for their potency against SARS-CoV-2 using NSP15 and fusion spike glycoprotein as targets. J Biomol Struct Dyn. 2020. https://doi.org/10.1080/07391102.2020.1762741.

Thông tin
Thông tin xuất bản

VirusDisease

Tập 32

46-54

Thông tin tác giả