Human Genetics And Molecular Medicine - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/107

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Subject: search.filters.subject.RNA dependent RNA polymerase

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    Withania somnifera phytochemicals possess SARS-CoV-2 RdRp and human TMPRSS2 protein binding potential
    (Springer, 2022-06-15T00:00:00) Prajapati, Kumari Sunita; Singh, Atul Kumar; Kushwaha, Prem Prakash; Shuaib, Mohd; Maurya, Santosh Kumar; Gupta, Sanjay; Senapati, Sabyasachi; Singh, Surya Pratap; Waseem, Mohammad; Kumar, Shashank
    Abstract: Coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has infected approximately 26�million people and caused more than 6�million deaths globally. Spike (S)-protein on the outer surface of the virus uses human trans-membrane serine protease-2 (TMPRSS2) to gain entry into the cell. Recent reports indicate that human dipeptidyl peptidase-4 inhibitors (DPP4 or CD26) could also be utilized to check the S-protein mediated viral entry into COVID-19 patients. RNA dependent RNA polymerase (RdRp) is another key virulence protein of SARS-CoV-2 life cycle. The study aimed to identify the potential anti-SARS-CoV-2 inhibitors present in Withania somnifera (Solanaceae) using computer aided drug discovery approach. Molecular docking results showed that flavone glycoside, sugar alcohol, and flavonoid present in W. somnifera showed ? 11.69, ? 11.61, ? 10.1, ? 7.71�kcal/mole binding potential against S-protein, CD26, RdRp, and TMPRSS2 proteins. The major standard inhibitors of the targeted proteins (Sitagliptin, VE607, Camostat mesylate, and Remdesivir) showed the ? 7.181, ? 6.6, ? 5.146, and ? 7.56�kcal/mole binding potential. Furthermore, the lead phytochemicals and standard inhibitors bound and non-bound RdRp and TMPRSS2 proteins were subjected to molecular dynamics (MD) simulation to study the complex stability and change in protein conformation. The result showed energetically favorable and stable complex formation in terms of RMSD, RMSF, SASA, Rg, and hydrogen bond formation. Drug likeness and physiochemical properties of the test compounds exhibited satisfactory results. Taken together, the present study suggests the presence of potential anti-SARS-CoV-2 phytochemicals in W. somnifera that requires further validation in in vitro and in vivo studies. Graphical Abstract: [Figure not available: see fulltext.] � 2022, The Author(s) under exclusive licence to Society for Plant Research.
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    Identification of Compounds from Curcuma longa with in Silico Binding Potential against SARS-CoV-2 and Human Host Proteins Involve in Virus Entry and Pathogenesis
    (Indian Pharmaceutical Association, 2021-12-07T00:00:00) Kumar, S.; Singh, A.K.; Kushwaha, P.P.; Prajapati, Kumari Sunita; Senapati, S.; Mohd, S.; Gupta, S.
    Severe acute respiratory syndrome coronavirus 2 and associated coronavirus disease 2019 is a newly identified human coronavirus has imposed a serious threat to global health. The rapid transmission of severe acute respiratory syndrome coronavirus 2 and its ability to spread in humans have prompted the development of new approaches for its treatment. Severe acute respiratory syndrome coronavirus 2 requires RNA-dependent RNA polymerases for life cycle propagation and Spike (S)-protein for attachment to the host cell surface receptors. The virus enters the human body with the assistance of a key functional host receptor dipeptidyl peptidase-4 primed by transmembrane serine protease 2 which are putative targets for drug development. We performed screening of 267 compounds from Curcuma longa L. (Zingiberaceae family) against the viral S-protein and RNA-dependent RNA polymerases and host receptor proteins dipeptidyl peptidase-4 and transmembrane serine protease 2 using in silico molecular docking. Compounds C1, ((4Z,6E)-1,5-dihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-4,6-dien- 3-one) and C6 ((4Z,6E)-1,5-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta-4,6- dien-3-one) exhibited tight binding to the S1 domain of the Spike protein than VE607 and with RNAdependent RNA polymerase protein more effectively than ribavirin and remdesivir. These compounds also interacted with the human host proteins dipeptidyl peptidase-4 and transmembrane serine protease 2 with higher efficiency than standard inhibitors sitagliptin and camostat mesylate. The lead compounds showed favorable free binding energy for all the studied protein-ligand complexes in Molecular mechanics/ Generalized born model and solvent accessibility analysis. Besides, other Curcuma longa compounds C14 and C23 exhibited almost similar potential against these target proteins. The structure based optimization and molecular docking studies have provided information on some lead Curcuma longa compounds with probability for advancement in preclinical research. � 2021 Indian Pharmaceutical Association. All rights reserved.