Research Journal of Pharmacy and Technology

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

De Novo In-silico Pharmacological Analysis of Herbal Phytoconstituents for Covid-19 Treatment


Affiliations
1 Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai-600116, Tamilnadu, India
     

   Subscribe/Renew Journal


Objective: The focus is to screen the phytoconstituents of various Indian medicinal plants using virtual screening tools against various targets of COVID-19 to develop potential compound for its treatment. Methods: The phytoconstituents of many herbal plants were screened based on literature review and then subjected to drug likeness property along with its bioactivity score. Docking of screened compounds with the targets of CoV being available default in the COVID-19 Docking Server tool based on Schrodinger maestro was demonstrated. Further, the docking was analysed using PyRx and AutoDock 4.2. The phytoconstituents were then taken for ADME estimation by ADME/T tool and SwissADME tool. The toxicity was predicted utilising TEST software. Results: Out of all, eleven phytoconstituents exhibited significant molecular properties and bioactivity score. After docking all compounds using various tools, their top binding scores were tabulated. It shows that the phytoconstituents Amritoside D and Tinocordifolin effectively produces significant action against COVID-19 when compared with the standard drugs currently been used. i.e., Favipiravir and Chloroquine. Further, it exhibited better absorption and distribution parameters for Pharmacokinetics of the drug. Hence, the toxicity estimation was also predicted focusing mainly on Oral Rat LD50 values. Conclusion: From all these results, it suggests that the compounds Amritoside D and Tinocordifolin produce significant results against COVID-19. Hence, further in-vitro and clinical studies have to be performed to develop drug for CoV treatment in a speedy way.

Keywords

Tinospora cordifolia, Drug likeness, Docking, TEST, ADME.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Mor S, Saini P, Wangnoo SK, Bawa T. Worldwide spread of COVID-19 Pandemic and risk factors among Co-morbid conditions especially Diabetes Mellitus in India. Research Journal of Pharmacy and Technology. 2020;13(5):2530-32.

  • Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, Hu Y, Tao ZW, Tian JH, Pei YY, Yuan ML. A new coronavirus associated with human respiratory disease in China. Nature. 2020 Mar;579(7798):265-9.

  • Zhu, N. et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 382, 2020. 727–733.

  • Zhang, L., Shen, F., Chen, F. and Lin, Z. Origin and evolution of the 2019 novel coronavirus. Clin. Infect. Dis. 2020.

  • Jiang S, Xia S, Ying T, Lu L. A novel coronavirus (2019-nCoV) causing pneumonia-associated respiratory syndrome. Cellular and molecular immunology (2020).

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

  • Woo PC, Huang Y, Lau SK, Yuen KY. Coronavirus genomics and bioinformatics analysis. viruses. 2010 Aug;2(8):1804-20.

  • Xue X, Yu H, Yang H, Xue F, Wu Z, Shen W, Li J, Zhou Z, Ding Y, Zhao Q, Zhang XC. Structures of two coronavirus main proteases: implications for substrate binding and antiviral drug design. J of virology. 2008 Mar 1;82(5):2515-27.

  • Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses—drug discovery and therapeutic options. Nature reviews Drug discovery. 2016 May;15(5):327.

  • Liu W, Morse JS, Lalonde T, Xu S. Learning from the past: possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019‐nCoV. Chembiochem. 2020 Feb 4.

  • Kong R, Yang G, Xue R, Liu M, Wang F, Hu J, Guo X, Chang S. COVID-19 Docking Server: An interactive server for docking small molecules, peptides and antibodies against potential targets of COVID-19. arXiv preprint arXiv:2003.00163. 2020 Feb 29.

  • Das C, Das D. An Overview on Therapeutic Potential of Traditional Fermented Biomedicines: Asava and Arista. Research Journal of Pharmacy and Technology. 2019;12(10):5067-75.

  • Patwardhan B, Chavan-Gautam P, Gautam M, Tillu G, Chopra A, Gairola S, Jadhav S. Ayurveda rasayana in prophylaxis of covid-19. Curr Sci. 2020 Apr 25;118:1158-60.

  • Alam N, Agrawal OP, Alam P, Agrawal S, Kaushik M, Dhari JS, Sharma OP. Natural Immunoenhancers. Research Journal of Pharmacy and Technology. 2011;4(10):1526-32.

  • Biswasroy P, Panda S, Das C, Das D, Kar DM, Ghosh G. Tinospora cordifolia-A plant with Spectacular natural immunobooster. Research Journal of Pharmacy and Technology. 2020; 13(2):1035-8.

  • Sahu P, Sharma A, Chatterjee T. Natural products with potent hypoglycemic activity. Research Journal of Pharmacy and Technology. 2010;3(3):650-6.

  • Sahu R, Mohapatra TK, Subudhi BB. Drug Interaction Potential of Tinospora cordifolia: A Review. Research Journal of Pharmacy and Technology. 2018;11(11):5179-83.

  • Choudhary N, Siddiqui MB, Azmat S, Khatoon S. Tinospora cordifolia: ethnobotany, phytopharmacology and phytochemistry aspects. International Journal of Pharmaceutical Sciences and Research. 2013 Mar 1;4(3):891

  • Singla A, Singla MA. Review of biological activities of" Tinospora Cordifolia. Webmed Central Pharm Sci. 2010;1:1-6.

  • Yang H, Yang M, Ding Y, Liu Y, Lou Z, Zhou Z, Sun L, Mo L, Ye S, Pang H, Gao GF. The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proceedings of the National Academy of Sciences. 2003 Nov 11;100(23):13190-5.

  • Ratia K, Saikatendu KS, Santarsiero BD, Barretto N, Baker SC, Stevens RC, Mesecar AD. Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme. Proceedings of the National Academy of Sciences. 2006 Apr 11;103(15):5717-22.

  • Alisi A, Panera N, Tozzi A. The G-quadruplex/helicase world as a potential antiviral approach against COVID-19.

  • Huang Q, Yu L, Petros AM, Gunasekera A, Liu Z, Xu N, Hajduk P, Mack J, Fesik SW, Olejniczak ET. Structure of the N-terminal RNA-binding domain of the SARS CoV nucleocapsid protein. Biochemistry. 2004 May 25;43(20):6059-63.

  • Ji'An Pan XP, Gao Y, Li Z, Lu X, Chen Y, Ishaq M, Liu D, DeDiego ML, Enjuanes L, Guo D. Genome-wide analysis of protein-protein interactions and involvement of viral proteins in SARS-CoV replication. PloS one. 2008;3(10).

  • Kim Y, Jedrzejczak R, Maltseva NI, Wilamowski M, Endres M, Godzik A, Michalska K, Joachimiak A. Crystal structure of Nsp15 endoribonuclease NendoU from SARS‐CoV‐2. Protein Science. 2020 Jan 1.

  • Lemus MR, Minasov G, Shuvalova L, Inniss NL, Kiryukhina O, Wiersum G, Kim Y, Jedrzejczak R, Enders M, Jaroszewski L, Godzik A. The crystal structure of nsp10-nsp16 heterodimer from SARS CoV-2 in complex with S-adenosylmethionine. bioRxiv. 2020 Jan 1.

  • Chen C, Huang J, Cheng Z, Wu J, Chen S, Zhang Y, Chen B, Lu M, Luo Y, Zhang J, Yin P. Favipiravir versus arbidol for COVID-19: a randomized clinical trial. MedRxiv. 2020 Jan 1.

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

  • Singh S, Gupta AK, Verma A. Molecular properties and bioactivity score of the Aloe vera antioxidant compounds-in order to lead finding. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2013;4(2):876-81.

  • Al-Saad HN, Kubba AA. Evaluation of New Thiosemcarbazides Derived from Captopril as Angiotensin-Converting Enzyme Inhibitors with Docking Study, and Predicted-ADMET Analysis. Research Journal of Pharmacy and Technology. 2020;13(6):2733-41.

  • Kong R, Yang G, Xue R, Liu M, Wang F, Hu J, Guo X, Chang S. COVID-19 Docking Server: An interactive server for docking small molecules, peptides and antibodies against potential targets of COVID-19. arXiv preprint arXiv:2003.00163. 2020 Feb 29.

  • Shankari B, Rambabu M, Jayanthi S. Identification and Designing Inhibitors for Hepatocellular Carcinoma by Targeting Claudin-10. Research Journal of Pharmacy and Technology. 2018;11(8):3529-33.

  • Singh K, Rambabu M, Jayanthi S. Designing BRAF specific inhibitors against melanoma. Research Journal of Pharmacy and Technology. 2018;11(8):3494-8.

  • Fereidoonnezhad M, Mostoufi A, Zali S, Eskandari M, Afshar D, Aliyan F. Molecular Docking and PLIF Studies of Novel Tacrine-Naphtoquinone Hybrids Based on Multi-Target-Directed Ligand Approach for Alzheimer’s Disease. Jundishapur Journal of Natural Pharmaceutical Products. 2018;13(2).

  • Kannadasan R, Emerson IA, Basha MS. Docking of HIV-1 with Neem using Autodock in Bioinformatics. Research Journal of Pharmacy and Technology. 2017;10(11):3877-80.

  • Machhar BK, Shah R, Bhimani B, Patel U, Daslaniya D, Patel G. Biological, pharmaceutical and analytical considerations of Caco-2 Monolayer. Research Journal of Pharmacy and Technology. 2013;6(4):336-44.

  • Kuche K, Bhargavi N, Dora CP, Jain S. Drug-phospholipid complex—a go through strategy for enhanced Oral bioavailability. AAPS PharmSciTech. 2019 Feb 1;20(2):43.

  • Rashid M. Design, Synthesis and ADMET prediction of Bis-benzimidazole as Anticancer agent. Bioorganic Chemistry. 2020 Jan 9:103576.

  • Golbamaki A, Cassano A, Lombardo A, Moggio Y, Colafranceschi M, Benfenati E. Comparison of in silico models for prediction of Daphnia magna acute toxicity. SAR and QSAR in Environmental Research. 2014 Aug 3;25(8):673-94.

  • Iyapparaja M, Sivakumar P. Metrics based evaluation for disease affection in distinct cities. Research Journal of Pharmacy and Technology. 2017;10(8):2487-91.

  • Thomson WM, Sudha M, Venkateswaramurthy N, Kumar RS. A Review on the Irrational Antibiotics usage in Pediatrics for Respiratory Tract Infections. Research Journal of Pharmacy and Technology. 2019;12(10):5126-30.

  • Rodriguez-Morales AJ, Bonilla-Aldana DK, Balbin-Ramon GJ, Rabaan AA, Sah R, Paniz-Mondolfi A, Pagliano P, Esposito S. History is repeating itself: probable zoonotic spillover as the cause of the 2019 novel Coronavirus Epidemic. Infez Med. 2020 Mar 1;28(1):3-5.

  • Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Bioscience trends. 2020 Feb 29;14(1):69-71.

  • Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, Montgomery SA, Hogg A, Babusis D, Clarke MO, Spahn JE. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nature Communications. 2020 Jan 10;11(1):1-4.

  • Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, Li SB, Wang HY, Zhang S, Gao HN, Sheng JF. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. Bmj. 2020 Feb 19; 368.

  • Mor S, Saini P, Wangnoo SK, Bawa T. Worldwide spread of COVID-19 Pandemic and risk factors among Co-morbid conditions especially Diabetes Mellitus in India. Research Journal of Pharmacy and Technology. 2020;13(5):2530-2.

  • Tindale L, Coombe M, Stockdale JE, Garlock E, Lau WY, Saraswat M, Lee YH, Zhang L, Chen D, Wallinga J, Colijn C. Transmission interval estimates suggest pre-symptomatic spread of COVID-19. MedRxiv. 2020 Jan 1.

  • Choudhari S, Priya VV, Gayathri R. Herbal Remedies for Swine Flu. Research Journal of Pharmacy and Technology. 2016;9(10):1789-92.

  • Rachmi E, Purnomo BB, Endharti AT, Fitri LE. In silico prediction of Anti-apoptotic BCL-2 proteins Modulation by Afzelin in MDA-MB-231 Breast cancer cell. Research Journal of Pharmacy and Technology. 2020;13(2):905-10.

  • Upmanyu N, Gupta S, Prakash BN, Garg G, Mishra P. Cheminformatics: A New Approach. Research Journal of Pharmacy and Technology. 2008;1(1):2-5.


Abstract Views: 146

PDF Views: 0




  • De Novo In-silico Pharmacological Analysis of Herbal Phytoconstituents for Covid-19 Treatment

Abstract Views: 146  |  PDF Views: 0

Authors

Safiya sultana T
Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai-600116, Tamilnadu, India
Umamaheswari S
Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai-600116, Tamilnadu, India
Sivakumar M
Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai-600116, Tamilnadu, India
Umar Khan S
Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai-600116, Tamilnadu, India

Abstract


Objective: The focus is to screen the phytoconstituents of various Indian medicinal plants using virtual screening tools against various targets of COVID-19 to develop potential compound for its treatment. Methods: The phytoconstituents of many herbal plants were screened based on literature review and then subjected to drug likeness property along with its bioactivity score. Docking of screened compounds with the targets of CoV being available default in the COVID-19 Docking Server tool based on Schrodinger maestro was demonstrated. Further, the docking was analysed using PyRx and AutoDock 4.2. The phytoconstituents were then taken for ADME estimation by ADME/T tool and SwissADME tool. The toxicity was predicted utilising TEST software. Results: Out of all, eleven phytoconstituents exhibited significant molecular properties and bioactivity score. After docking all compounds using various tools, their top binding scores were tabulated. It shows that the phytoconstituents Amritoside D and Tinocordifolin effectively produces significant action against COVID-19 when compared with the standard drugs currently been used. i.e., Favipiravir and Chloroquine. Further, it exhibited better absorption and distribution parameters for Pharmacokinetics of the drug. Hence, the toxicity estimation was also predicted focusing mainly on Oral Rat LD50 values. Conclusion: From all these results, it suggests that the compounds Amritoside D and Tinocordifolin produce significant results against COVID-19. Hence, further in-vitro and clinical studies have to be performed to develop drug for CoV treatment in a speedy way.

Keywords


Tinospora cordifolia, Drug likeness, Docking, TEST, ADME.

References