Computational studies of drugs for possible action against Covid-19 infections

  • Ganesh Prasad Mishra Kharvel Subharti College of Pharmacy, Swami Vivekanand Subharti University, Subhartipuram, NH-58, Delhi-Haridwar Bypass Road, Meerut, U.P, India, 250005
  • Debadash Panigrahi Drug Research Laboratory, Nodal Research Centre, College of Pharmaceutical Sciences, Puri, Baliguali, Puri- Konark Marine Drive road, Puri, Odisha, India, 752002

Abstract

SARS-Cov-2 has emerged highly contagious viral infections so far and posed a global threat with significant human casualties and severe economic losses. There is urgent demand to develop rational therapies to control the drastic spread of the virus. Although there is no specific regimens are available to combat this pandemic situation so far. An attempt was made to perform Insilco studies of drugs applicable to respiratory tract infections with crucial SARS-COV-2 main protease (M-pro) enzyme. Insilco docking study was performed with Molegro Virtual Docker 5.5    on number of available medications of different categories specified for respiratory tract infections.Result indicates that Azithromycin, Dexamethasone and Remdesivir are highly effective and mainly interacted with key amino acid residues with hydrogen bonds and displayed excellent docking score -133, -141 and -153 kcal/mole respectively.


This study advocates the possible use Azithromycin, Dexamethasone and Remdesivir drugs in combination to battle this pandemic condition. Further, this study will provide rationalized drugs and target for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.


Keywords: Viruses, SARS-COV-2, Covid-19, Drugs, Computational docking Studies, Drug Design

Keywords: Viruses, SARS-COV-2, Covid-19, Computational docking Studies, Drug Design

Downloads

Download data is not yet available.

Author Biographies

Ganesh Prasad Mishra, Kharvel Subharti College of Pharmacy, Swami Vivekanand Subharti University, Subhartipuram, NH-58, Delhi-Haridwar Bypass Road, Meerut, U.P, India, 250005

Kharvel Subharti College of Pharmacy, Swami Vivekanand Subharti University, Subhartipuram, NH-58, Delhi-Haridwar Bypass Road, Meerut, U.P, India, 250005

Debadash Panigrahi, Drug Research Laboratory, Nodal Research Centre, College of Pharmaceutical Sciences, Puri, Baliguali, Puri- Konark Marine Drive road, Puri, Odisha, India, 752002

Drug Research Laboratory, Nodal Research Centre, College of Pharmaceutical Sciences, Puri, Baliguali, Puri- Konark Marine Drive road, Puri, Odisha, India, 752002

References

1. 2020 Novel coronavirus (2019-nCoV) situation report -202. Organization, W.H; October 23, 2020.
2. Hussin R. Siddappa NB. 2020, The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak, Journal of autoimmunology, 2020; 109:102433.
3. Cynthia L, Qiongqiong Z, Yingzhu L, Garner LV, Steve P, Steve P, Watkins S.P, Carter L.J, Smoot J, Gregg AC, Daniels AD, Jervey S, Albaiu D, Research and Development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Central Science, 2020; 6(3):315-333.
4. Shaha B, Modia P, Sagara SR, In silico studies on therapeutic agents for COVID-19: Drug repurposing approach, Life Science, 2020; 252:117652.
5. Pan C, Chen L, Lu C, Zhang W, Xia J A, Sklar MC, Du B, Brochard L, Qiu Haibo, Lung Recruitability in COVID-19-associated Acute Respiratory Distress Syndrome: A Single-Center Observational Study, American Journal of Respiratory Critical Care Medicine , 2020; 20(1):1294-1297.
6. Bharadwaj S, Lee KE, Dwivedi VD, Kang SG, Computational insights into tetracyclines as inhibitors against SARS-CoV-2Mpro via combinatorial molecular simulation calculations, Life Science, 2020; 257:118080.
7. Xue X, Yu H, Yang H, Xue F, Wu Z, Shen W, Li J, Zhou Z, Ding Y, Zhao Q, Zhang XC, Liao M, Bartlam M, Rao Z, Structures of Two Corona virus Main Proteases : Implications for Substrate Binding and Antiviral Drug Design, Journal of Virology, 2008; 82(5):2515-2527.
8. Kandeel M, Altaher A, Alnazawi M, Molecular dynamics and inhibition of MERS CoV papain-like protease by small molecule imidazole and aminopurine derivatives. Letters Drug Design and Discovery, 2019; 16(5):584–591.
9. L,i YH, Hu CY, Wu NP, Yao HP, Li LJ, Molecular characteristics, functions, and related pathogenicity of MERS-CoV proteins, Engineering, 2019; 5(5):940–947.
10. Pillaiyar T, Meenakshisundaram S, Manickam M, Recent discovery and development of inhibitors targeting coronaviruses. Drug Discovery Today, 2020; 25(4):668-88.
11. Zumla A, Chan JFW, Azhar EI, Hui DSC, Yuen KY, Coronaviruses-drug discovery and therapeutic options, Nat Rev Drug Discovery,2016; 15(5):327-347.
12. Dai W, Zhang B, Jiang XM, Su H, Li J, Zhao Y, Xie X, Jin Z, Liu F, Li C, Li Y, Bai F, Wang H, Cheng X, Cen X, Hu S,Yang X, Wang J, Liu X, Xiao G, Jiang H, Rao Z, Zhang LK, Xu Y, Yang H, Liu H, Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease, Science, 2020; 368 (6497):1331-1335.
13. Yang H, Xie W, Xue X, Yang K, Ma J, Liang W, Zhao Q, Zhou Z, Pei D, Ziebuhr J, Hilgenfeld R, Yuen KY, Wong L, Gao G, Chen S, Chen Z, Ma D, Bartlam M, Rao Z, Design of wide-spectrum inhibitors targeting coronavirus main proteases, PLoS Biology, 2005; 3(10):1742-1752.
14. Hall Jr. DC, Ji HF, A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease. Travel Medicine Infectionus Disease, 2020; 35:101646.
15. Zhanga J, Xie B, Hashimoto, K. Current status of potential therapeutic candidates for the COVID-19 crisis. Brain Behaviour Immunology, 2020; 87:59–73.
16. Donald C, Hall Jr., Hai-Feng Ji, A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease. Travel Medicine Infectious Disease, 2020; 35:101646.
17. Thomsen R, Christensen MH MolDock: a new technique for high-accuracy molecular docking, Journal of Medicinal Chemistry, 2006; 49(11):3315-3321
18. Carlesso A, Chintha C, Gorman AM, Samali A, Eriksson LA, Merits and pitfalls of conventional and covalent docking in identifying new hydroxyl aryl aldehyde like compounds as human IRE1 inhibitors, Scientific Report, 2019; 9(1):3407.
19. Marinho EM, Batista de Andrade Neto J, Silva J, Rocha da Silva C, Cavalcanti BC, Marinho ES, Nobre Júnior HV, Virtual screening based on molecular docking of possible inhibitors of Covid-19 main protease. Microbiological Pathogenesis, 2020; 148:104365.
Statistics
37 Views | 31 Downloads
How to Cite
1.
Mishra GP, Panigrahi D. Computational studies of drugs for possible action against Covid-19 infections. JDDT [Internet]. 15Nov.2020 [cited 26Nov.2020];10(6):99-05. Available from: http://jddtonline.info/index.php/jddt/article/view/4381