Asian Journal of Pharmaceutical Research and Health Care

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An In Silico Approach for Identification of Inhibitors as a Potential Therapeutics Targeting SARS-Cov-2 Protease


Affiliations
1 Infectious Diseases Research Lab, Department of Zoology, Kakatiya University, Hanamkonda, Warangal – 506009, Telangana, India
 

SARS-CoV-2 caused COVID-19 which is pandemic and is a global health emergency. Protease is the drug target for corona viruses and this enzyme processes the production of polyproteins from the viral RNA. Objective of this study is to find the inhibitors against SARS-Cov-2 protease. AutoDock 4.2 was used for docking calculations. To check different molecules, test ligands like lopinavir, ritonavir (retroviral drugs) and hydroxychloroquine (anti-malarial drug) were docked against our target enzyme protease retrieved from Protein Data Bank. With respect to docking free binding energy, it is revealed that, Hydroxychloroquine has the lowest binding energy followed by Ritonavir and Lopinavir binds significantly to target enzyme protease. The results of this study provide a solid base for the use of Hydroxychloroquine against COVID-19 treatment. The interactions from structural models at the protease active site of virus can offer a valuable guide for more strategies for structure-based medications and the development of more operative inhibitors of SARS-CoV-2 protease.

Keywords

COVID-19, Hydroxychloroquine, In Silico, Lopinavir, Ritonavir, SARS-Cov-2i Protease.
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  • Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si H-R, Zhu Y, Li B, Huang C-L, Chen H-D, Chen J, Luo Y, Guo H, Jiang R-D, Liu M-Q, Chen Y, Shen X-R, Wang X, Zheng X-S, Zhao K, Chen Q-J, Deng F, Liu L-L, Yan B, Zhan F-X, Wang Y-Y, Xiao G-F, Shi Z-L. A pneumonia outbreak associated with a new corona virus of probable bat origin. Nature. 2020; 579:270-73. https://doi.org/10.1038/s41586-020-2012-7. PMid: 32015507, PMCid: PMC7095418.

  • Wu F, Zhao S, Yu B, Chen Y-M, Wang W, Song Z-G, Hu Y, Tao Z-W, Tian J-H, Pei Y-Y, Yuan M-L, Zhang Y-L, Dai F-H, Liu Y, Wang Q-M, Zheng J-J, Xu L, Holmes EC, Zhang Y-Z. A new corona virus associated with human respiratory disease in China. Nature. 2020; 579:265-69. https://doi.org/10.1038/s41586-020-2008-3. PMid: 32015508, PMCid: PMC7094943.

  • World Health Organization. Pneumonia, 2020 of unknown cause - China. Available from: https://www.who.int/csr/don/05-january-2020-pneumonia-of-unkown-causechina/en/.

  • Giovanetti M, Benvenuto D, Angeletti S, Ciccozzi M. The first two cases of 2019-nCoV in Italy: Where they come from? J. Med. Virol. 2020. PMID: 32022275. https://doi.org/10.1002/jmv.25699. PMid: 32022275, PMCid: PMC7166327.

  • Shigemura J, Ursano RJ, Morganstein JC, Kurosawa M, Benedek DM. Public responses to the novel 2019-coronavirus (2019-nCoV) in Japan: Mental health consequences and target populations. Psychiatry Clin. Neurosci. 2020. PMID: 32034840. https://doi.org/10.1111/pcn.12988. PMid: 32034840, PMCid: PMC7168047.

  • WHO Severe Acute Respiratory Syndrome (SARS) Weekly. Epidemiol. Rep. 2020; 78:86.

  • Indian Council of Medical Research (ICMR), Government of India. COVID-19 cases. Available online: https://www.icmr.nic.in/content/covid-19.

  • Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R. Corona virus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs. Science. 2003; 300:1763-67. https://doi.org/10.1126/science.1085658. PMid: 12746549.

  • Nadaraia NS, Amiranashvili LS, Merlani M, Kakhabrishvili ML, Barbakadze NN, Geronikaki A, Petrou A, Poroikov V, Ciric A, Glamoclija J, et al. Novel antimicrobial agents’ discovery among the steroid derivatives. Steroids. 2019; 144:52-65. https://doi.org/10.1016/j.steroids.2019.02.012. PMid: 30776376.

  • Kouatly O, Eleftheriou P, Petrou A, Hadjipavlou-Litina D, Geronikaki A. Docking assisted design ofnnovel 4-adamantanyl-2-thiazolylimino-5-arylidene-4-thiazolidinones as potent NSAIDs. SAR QSAR Environ. Res. 2018; 29:83-101. https://doi.org/10.1080/1062936X.2017.1410220. PMid: 29299942.

  • https://www.rcsb.org/structure/6LU7. Accessed on 23 March 2020.

  • Chang MW, Ayeni C, Breuer S. Virtual screening for HIV protease inhibitors: A comparison of AutoDock 4 and vina. PLoS ONE. 2010; 5:119-55. https://doi.org/10.1371/journal.pone.0011955. PMid: 20694138, PMCid: PMC2915912.

  • Park H, Lee J, Lee S. Critical assessment of the automated AutoDock as a new docking tool for virtual screening. Proteins. 2006; 65:549-54. https://doi.org/10.1002/prot.21183. PMid: 16988956.

  • Filimonov DA, Lagunin AA, Gloriozova TA, Rudik AV, Druzhilovskiy DS, Pogodin PV, Poroikov VV. Prediction of the biological activity spectra of organic compounds using the PASS online web resource. Chem. Heterocycl. Compd. 2014; 50:444-57. https://doi.org/10.1007/s10593-014-1496-1.

  • Geronikaki A, Dearden JC, Filimonov D, Galaeva I, Garibova TL, Gloriozova T, Kraineva V, Lagunin A, Macaev FZ, Molodavkin G, et al. Design of new cognition enhancers: From computer prediction to synthesis and biological evaluation. J. Med. Chem. 2004; 47:2870-76. https://doi.org/10.1021/jm031086k. PMid: 15139765.

  • Geronikaki A, Babaev E, Dearden J, Dehaen W, Filimonov D, Galaeva I, Kraineva V, Lagunin A, Macaev F, Molodavkin, G, et al. Design, synthesis, computational and biological evaluation of new anxiolytics. Bioorg. Med. Chem. 2004; 12:6559-68. https://doi.org/10.1016/j.bmc.2004.09.016. PMid: 15556772.

  • Dayam R, Neamati N. Active site binding modes of the betadiketoacids: A multi-active site approach in HIV-1 integrase inhibitor design. Bioorg. Med. Chem. 2004; 12:6371-81. https://doi.org/10.1016/j.bmc.2004.09.035. PMid: 15556755.


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  • An In Silico Approach for Identification of Inhibitors as a Potential Therapeutics Targeting SARS-Cov-2 Protease

Abstract Views: 321  |  PDF Views: 252

Authors

Estari Mamidala
Infectious Diseases Research Lab, Department of Zoology, Kakatiya University, Hanamkonda, Warangal – 506009, Telangana, India
Rakesh Davella
Infectious Diseases Research Lab, Department of Zoology, Kakatiya University, Hanamkonda, Warangal – 506009, Telangana, India
Swapna Gurrapu
Infectious Diseases Research Lab, Department of Zoology, Kakatiya University, Hanamkonda, Warangal – 506009, Telangana, India

Abstract


SARS-CoV-2 caused COVID-19 which is pandemic and is a global health emergency. Protease is the drug target for corona viruses and this enzyme processes the production of polyproteins from the viral RNA. Objective of this study is to find the inhibitors against SARS-Cov-2 protease. AutoDock 4.2 was used for docking calculations. To check different molecules, test ligands like lopinavir, ritonavir (retroviral drugs) and hydroxychloroquine (anti-malarial drug) were docked against our target enzyme protease retrieved from Protein Data Bank. With respect to docking free binding energy, it is revealed that, Hydroxychloroquine has the lowest binding energy followed by Ritonavir and Lopinavir binds significantly to target enzyme protease. The results of this study provide a solid base for the use of Hydroxychloroquine against COVID-19 treatment. The interactions from structural models at the protease active site of virus can offer a valuable guide for more strategies for structure-based medications and the development of more operative inhibitors of SARS-CoV-2 protease.

Keywords


COVID-19, Hydroxychloroquine, In Silico, Lopinavir, Ritonavir, SARS-Cov-2i Protease.

References





DOI: https://doi.org/10.18311/ajprhc%2F2020%2F25080