Investigating into the molecular interactions of flavonoids targeting NS2B-NS3 protease from ZIKA virus through <i>in-silico</i> approaches

Yadav, Rakhi; Selvaraj, Chandrabose; Aarthy, Murali; Kumar, Prateek; Kumar, Ankur; Giri, Rajanish

doi:10.1080/07391102.2019.1709546

Cited by 28 publications

(17 citation statements)

References 56 publications

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“…No inhibitory effect was observed at any dose for the other compounds. These data, obtained on cell cultures, did not confirm the predictive inhibitory activity of luteolin, apigenin, and rutin as inhibitors of the ZIKV NS2B-NS3 protease, as identified by molecular docking [17,18]. Furthermore, the ability of quercetin 3-O-glucoside to inhibit ZIKV in vitro, as reported in the literature, was not reproduced [19].…”

Section: Resultsmentioning

confidence: 70%

Punica granatum Leaf Ethanolic Extract and Ellagic Acid as Inhibitors of Zika Virus Infection

et al. 2020

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Zika virus, an arthropod-borne flavivirus, is an emerging healthcare threat worldwide. Zika virus is responsible for severe neurological effects, such as paralytic Guillain-Barrè syndrome, in adults, and also congenital malformations, especially microcephaly. No specific antiviral drugs and vaccines are currently available, and treatments are palliative, but medicinal plants show great potential as natural sources of anti-Zika phytochemicals. This study deals with the investigation of the composition, cytotoxicity, and anti-Zika activity of Punica granatum leaf ethanolic extract, fractions, and phytoconstituents. P. granatum leaves were collected from different areas in Italy and Greece in different seasons. Crude extracts were analyzed and fractionated, and the pure compounds were isolated. The phytochemical and biomolecular fingerprint of the pomegranate leaves was determined. The antiviral activities of the leaf extract, fractions, and compounds were investigated against the MR766 and HPF2013 Zika virus strains in vitro. Both the extract and its fractions were found to be active against Zika virus infection. Of the compounds isolated, ellagic acid showed particular anti-Zika activities, with EC50 values of 30.86 µM for MR766 and 46.23 µM for HPF2013. The mechanism of action was investigated using specific antiviral assays, and it was demonstrated that ellagic acid was primarily active as it prevented Zika virus infection and was able to significantly reduce Zika virus progeny production. Our data demonstrate the anti-Zika activity of pomegranate leaf extract and ellagic acid for the first time. These findings identify ellagic acid as a possible anti-Zika candidate compound that can be used for preventive and therapeutic interventions.

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Section: Resultsmentioning

confidence: 70%

Punica granatum Leaf Ethanolic Extract and Ellagic Acid as Inhibitors of Zika Virus Infection

et al. 2020

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“…OPLS 2005 forcefield is used for calculating bonded and non-bonded parameters such as van der Waal interactions (Friesner et al, 2006;Halgren et al, 2004). For the detailed protocol of Glide, see our previously reported articles (Kumar et al, 2019;Kumar, Saumya et al, 2020;Sharma et al, 2017;Yadav et al, 2020). The interaction of docked compounds with M pro is analyzed in the 4 Å cutoff of active site.…”

Section: Docking Studies Of M Pro With Approved Drugsmentioning

confidence: 99%

Reprofiling of approved drugs against SARS-CoV-2 main protease: an in-silico study

Kumar

Bhardwaj

Kumar

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Given the COVID-19 pandemic, currently, there are many drugs in clinical trials against this virus. Among the excellent drug targets of SARS-CoV-2 are its proteases (Nsp3 and Nsp5) that plays vital role in polyprotein processing giving rise to functional nonstructural proteins, essential for viral replication and survival. Nsp5 (also known as M pro) hydrolyzes replicase polyprotein (1ab) at eleven different sites. For targeting M pro , we have employed drug repurposing approach to identify potential inhibitors of SARS-CoV-2 in a shorter time span. Screening of approved drugs through docking reveals Hyaluronic acid and Acarbose among the top hits which are showing strong interactions with catalytic site residues of M pro. We have also performed docking of drugs Lopinavir, Ribavirin, and Azithromycin on SARS-CoV-2 M pro. Further, binding of these compounds (Hyaluronic acid, Acarbose, and Lopinavir) is validated by extensive molecular dynamics simulation of 500 ns where these drugs show stable binding with M pro. We believe that the high-affinity binding of these compounds will help in designing novel strategies for structure-based drug discovery against SARS-CoV-2.

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“…MD simulation was performed for the timescale of 20 nano seconds (ns) using OPLS-3e force field. The results of RMSD and hydrogen bonds were analysed using the Desmond simulation interaction analysis (Yadav et al., 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Targeting COVID-19 (SARS-CoV-2) main protease through active phytochemicals of ayurvedic medicinal plants – Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) – a molecular docking study

Shree

Mishra

Selvaraj

et al. 2020

Journal of Biomolecular Structure and Dynamics

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COVID-19 (Coronavirus disease 2019) is a transmissible disease initiated and propagated through a new virus strain SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) since 31 st December 2019 in Wuhan city of China and the infection has outspread globally influencing millions of people. Here, an attempt was made to recognize natural phytochemicals from medicinal plants, in order to reutilize them against COVID-19 by the virtue of molecular docking and molecular dynamics (MD) simulation study. Molecular docking study showed six probable inhibitors against SARS-CoV-2 M pro (Main protease), two from Withania somnifera (Ashwagandha) (Withanoside V [10.32 kcal/mol] and Somniferine [9.62 kcal/mol]), one from Tinospora cordifolia (Giloy) (Tinocordiside [8.10 kcal/mol]) and three from Ocimum sanctum (Tulsi) (Vicenin [8.97 kcal/mol], Isorientin 4 0-O-glucoside 2 00-O-p-hydroxybenzoagte [8.55 kcal/mol] and Ursolic acid [8.52 kcal/mol]). ADMET profile prediction showed that the best docked phytochemicals from present work were safe and possesses drug-like properties. Further MD simulation study was performed to assess the constancy of docked complexes and found stable. Hence from present study it could be suggested that active phytochemicals from medicinal plants could potentially inhibit M pro of SARS-CoV-2 and further equip the management strategy against COVID-19-a global contagion. HIGHLIGHTS Holistic approach of Ayurvedic medicinal plants to avenge against COVID-19 pandemic. Active phytoconstituents of Ayurvedic medicinal plants Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) predicted to significantly hinder main protease (M pro or 3Cl pro) of SARS-CoV-2. Through molecular docking and molecular dynamic simulation study, Withanoside V, Somniferine, Tinocordiside, Vicenin, Ursolic acid and Isorientin 4 0-O-glucoside 2 00-O-p-hydroxybenzoagte were anticipated to impede the activity of SARS-CoV-2 M pro. Drug-likeness and ADMET profile prediction of best docked compounds from present study were predicted to be safe, drug-like compounds with no toxicity.

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Investigating into the molecular interactions of flavonoids targeting NS2B-NS3 protease from ZIKA virus through in-silico approaches

Cited by 28 publications

References 56 publications

Punica granatum Leaf Ethanolic Extract and Ellagic Acid as Inhibitors of Zika Virus Infection

Punica granatum Leaf Ethanolic Extract and Ellagic Acid as Inhibitors of Zika Virus Infection

Reprofiling of approved drugs against SARS-CoV-2 main protease: an in-silico study

Targeting COVID-19 (SARS-CoV-2) main protease through active phytochemicals of ayurvedic medicinal plants – Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) – a molecular docking study

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