Human Genetics And Molecular Medicine - Research Publications

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Subject: search.filters.subject.Curcuma longa

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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.
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    Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and simulation studies
    (Taylor and Francis Ltd., 2020-06-01T00:00:00) Gupta, Sanjay; Singh, Atul Kumar; Kushwaha, Prem Prakash; Prajapati, Kumari Sunita; Shuaib, Mohd; Senapati, Sabyasachi; Kumar, Shashank
    Coronaviruses are contagious pathogens primarily responsible for respiratory and intestinal infections. Research efforts to develop antiviral agents against coronavirus demonstrated the main protease (Mpro) protein may represent effective drug target. X-ray crystallographic structure of the SARS-CoV2 Mpro protein demonstrated the significance of Glu166, Cys141, and His41 residues involved in protein dimerization and its catalytic function. We performed in silico screening of compounds from Curcuma longa L. (Zingiberaceae family) against Mpro protein inhibition. Employing a combination of molecular docking, scoring functions, and molecular dynamics simulations, 267 compounds were screened by docking on Mpro crystallographic structure. Docking score and interaction profile analysis exhibited strong binding on the Mpro catalytic domain with compounds C1 (1E,6E)-1,2,6,7-tetrahydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) and C2 (4Z,6E)?1,5?dihydroxy?1,7?bis(4?hydroxyphenyl)hepta?4,6?dien?3?one as lead agents. Compound C1 and C2 showed minimum binding score (�9.08 and �8.07 kcal/mole) against Mpro protein in comparison to shikonin and lopinavir (? ?5.4 kcal/mole) a standard Mpro inhibitor. Furthermore, principal component analysis, free energy landscape and protein-ligand energy calculation studies revealed that these two compounds strongly bind to the catalytic core of the Mpro protein with higher efficacy than lopinavir, a standard antiretroviral of the protease inhibitor class. Taken together, this structure based optimization has provided lead on two natural Mpro inhibitors for further testing and development as therapeutics against human coronavirus. Communicated by Ramaswamy H. Sarma. � 2020 Informa UK Limited, trading as Taylor & Francis Group.