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Kumar, Arun H.S.
Preferred name
Kumar, Arun H.S.
Official Name
Kumar, Arun H.S.
Research Output
Now showing 1 - 5 of 5
- PublicationMolecular docking of natural compounds from tulsi (Ocimum sanctum) and neem (Azadirachta indica) against SARS-CoV-2 protein targetsBackground: Antiviral activity of tulsi and neem extracts are widely reported. Selected natural compounds from tulsi and neem were hence screened for their efficacy against SARS-CoV-2 targets. Materials and Methods : Using molecular docking tools, the binding efficacy of natural compounds from tulsi and neem were tested against three key SARS-CoV-2 targets i.e., 1) surface glycoprotein (6VSB) responsible for viral attachment, 2) RNA dependent RNA polymerase (6M71) responsible for viral replication and 3) main protease (6Y84) responsible for viral replication. Results: Methyl eugenol, oleanolic acid and ursolic acid had high binding efficacy against surface spike glycoprotein and RNA polymerase of SARS-CoV-2. Epoxyazadiradione, Gedunin, Methyl eugenol, Oleanolic acid and Ursolic acid showed high binding efficacy against the main protease of SARS-CoV-2. Binding efficacy of natural compounds from tulsi and neem was superior to that of the standard drugs Lopinavir/Ritonavir and Remdesivir. Conclusion: Natural compounds from tulsi and neem have high binding efficacy against SARS-CoV-2 targets involved in viral attachment and replication, hence will be useful in the management of infection caused by SARS-CoV-2.
306 - PublicationEfficacy of natural compounds from Tinospora cordifolia against SARS-CoV-2 protease, surface glycoprotein and RNA polymerase.Background: Antiviral activity of natural compounds from Tinospora cordifolia (Amritaballi) were evaluated for their efficacy against SARS-CoV-2 targets involved in virus attachment and replication.Materials and Methods: The binding efficacy (binding affinity, Ki and IC50 values) of natural compounds from Tinospora cordifolia were tested using Insilco tools against four key SARS-CoV-2 targets i.e., 1) surface glycoprotein (6VSB) and 2) Receptor binding domain (6M0J) both responsible for attachment of the virus to host cell, 3) RNA dependent RNA polymerase (6M71) and 4) main protease (6Y84) responsible for replication of the virus in the host cell.Results: Berberine, Isocolumbin, Magnoflorine and Tinocordiside showed high binding efficacy against all the four key SARS-CoV-2 targets. Tinocordiside and Isocolumbin showed IC50 value of < 1 µM against both 6Y84 and 6VSB.Conclusion: At least four natural compounds from Tinospora cordifolia showed high binding efficacy against SARS-CoV-2 targets involved in attachment and replication of the virus. Hence validating the merit of using Tinospora cordifolia in the clinical management of infection caused by SARS-CoV-2.
814 - PublicationNetwork proteins of angiotensin-converting enzyme 2 but not angiotensin-converting enzyme 2 itself are host cell receptors for SARS-Coronavirus-2 attachmentBackground: Coronaviruses causing severe acute respiratory syndrome (SARS-CoV) are known to enter the host cells by attaching to the membrane bound angiotensin-converting enzyme 2 (ACE2). Using molecular docking the efficiency of interaction between SARS-CoV-2 surface proteins and ACE2 network proteins was assessed.Materials and Methods: The ACE2 protein network was identified using the STRING database. The reported SARS-CoV-2 target proteins were searched in the protein data bank and uniport database. The protein-protein interactions were assessed by molecular docking using the Chimera software. The PubChem database was searched for known inhibitors of host cell receptors interacting with SARS-CoV-2 surface proteins. Molecular docking was performed to evaluate the binding efficacy of these compounds against the SARS-CoV-2 targets using AutoDock Vina and the docked protein-ligand complex were visualised using the Chimera and PyMOL software.Results: A low binding affinity was observed between SARS-CoV-2 spike proteins (protein S, M and 6YLA) and ACE2. Coronaviruses are also reported to bind to dipeptidyl peptidase 4 (DPP4), which is a network protein of ACE2. Network analysis showed five membrane proteins associated with ACE2. The ACE2 network proteins were assessed for their binding affinity with all known SARS-CoV-2 surface proteins. The SARS-CoV-2 surface proteins showed preferential binding to network proteins such as DPP4 and Meprin A alpha but not ACE2. The binding efficacy (affinity (-5.86 to -7.10 Kcal/mol), Ki (6.32 – 22.04 mM) and IC50 (12.63 – 113.71 mM) values) of DPP4 inhibitors (saxagliptin and sitagliptin) against SARS-CoV-2 surface proteins, was observed to be at a therapeutically feasible concentration to prevent SARS-CoV-2 attachment and entry into host cells.Conclusion: SARS-CoV-2 surface proteins has better interactions with DPP4 and Meprin A alpha host cells receptors rather than ACE2. DPP4 inhibitors (saxagliptin and sitagliptin) by binding with SARS-CoV-2 surface proteins may be helpful in preventing the virus entry into the host cells.
166 - PublicationMolecular profiling of Neprilysin expression and its interactions with SARS-CoV-2 spike proteins to develop evidence base pharmacological approaches for therapeutic interventionNeprilysin due to its peptidase activity is involved in several physiological and pathological processes. Recently our group has reported the association of neprilysin with angiotensin-converting enzyme 2 (ACE2) network proteins which facilitate the entry of SARS-COV2 virus. The potential role of neprilysin beyond its peptidase activity is not known. Using the established sequence analysis and molecular docking tools, this study evaluated the molecular profile of neprilysin interaction with SARS-COV2 virus proteins. Human neprilysin protein showed a significant sequence similarity with SARS-COV2 spike protein, which was further confirmed by observation of considerable interaction in the molecular docking. Human neprilysin protein was also found to additionally interact with SARS-COV2 proteins facilitating virus replication. The potential of neprilysin inhibitors (Sacubitril and Sacubitrilat) to interfere with neprilysin and SARS-COV2 proteins interactions was assessed. The neprilysin inhibitors showed binding efficacy within therapeutically feasible concentration range (1 to 150 uM). This study while reporting a novel role of neprilysin as potential receptor for SARS-COV2 virus, highlights the merit in assessing clinical efficacy of neprilysin inhibitors for the management of SARS-COV2 infection.
190 - PublicationAcetamido-propanoic Acid Derived Compounds as Protease Inhibitors to Target CoronavirusesBackground: Coronavirus infection as evolved into a major pandemic and is currently being treated using established antiviral agents developed for other similar viruses. Considering the frequent mutations rate in this virus, novel drugs will be necessary for effective treatment in future. Hence this study evaluated the potential of acetamido-propanoic acid derived compounds as viral protease inhibitors. Materials and Methods: Using cheminformatics approach novel acetamido-propanoic acid derived compounds were designed and their binding efficacy against the Coronavirus 2019 (Covid-19) protease was tested using Insilco pharmacology. Results: STGYC compounds had physico-chemical features favourable for developing them for potential clinical use. The binding efficacy of STGYC compounds against covid-19 protease was similar to that of favipiravir, which currently being reported to be effective in treating coronavirus infection. Conclusion: STGYC compounds shown favourable features to be further evaluated and developed as viral protease inhibitors.
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