Potential phytochemical inhibitors of SARS-CoV-2 helicase Nsp13: a molecular docking and dynamic simulation study

Vivek-Ananth, R.P.; Krishnaswamy, S.; Samal, Areejit

doi:10.1007/s11030-021-10251-1

Cited by 33 publications

(20 citation statements)

References 54 publications

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“…Amongst other helicase drug screening studies, a docking study screened nucleoside analogs for helicase activity and identified pritelivir as a potential drug candidate [ 65 ]. Another molecular docking and MD simulation study identified potential natural product inhibitors of helicase targeting the ATP-binding site which included picrasidine-N and -M, epiexcelsin, isorhoeadine, and euphorbetin [ 66 ]. Another study used fragment screening to identify possible druggable pockets on the Nsp13 helicase, identifying a favorable allosteric site on the N-terminal zinc binding domain that is a Nsp8:Nsp13 protein–protein interaction site [ 67 ].…”

Section: Resultsmentioning

confidence: 99%

Potential COVID-19 Therapies from Computational Repurposing of Drugs and Natural Products against the SARS-CoV-2 Helicase

Piplani

Singh

Winkler

et al. 2022

IJMS

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Repurposing of existing drugs is a rapid way to find potential new treatments for SARS-CoV-2. Here, we applied a virtual screening approach using Autodock Vina and molecular dynamic simulation in tandem to screen and calculate binding energies of repurposed drugs against the SARS-CoV-2 helicase protein (non-structural protein nsp13). Amongst the top hits from our study were antivirals, antihistamines, and antipsychotics, plus a range of other drugs. Approximately 30% of our top 87 hits had published evidence indicating in vivo or in vitro SARS-CoV-2 activity. Top hits not previously reported to have SARS-CoV-2 activity included the antiviral agents, cabotegravir and RSV-604; the NK1 antagonist, aprepitant; the trypanocidal drug, aminoquinuride; the analgesic, antrafenine; the anticancer intercalator, epirubicin; the antihistamine, fexofenadine; and the anticoagulant, dicoumarol. These hits from our in silico SARS-CoV-2 helicase screen warrant further testing as potential COVID-19 treatments.

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Section: Resultsmentioning

confidence: 99%

Potential COVID-19 Therapies from Computational Repurposing of Drugs and Natural Products against the SARS-CoV-2 Helicase

Piplani

Singh

Winkler

et al. 2022

IJMS

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“…The key amino acid residues of the ATP-binding site are six in number and are Lys288, Ser289, Asp374, Glu375, Gln404, and Arg567 [ 52 ]. Dihydroxyacidissiminol showed the predicted binding energy of −7.6 kcal/mol with Nsp13 helicase.…”

Section: Resultsmentioning

confidence: 99%

“…Outbreaks of nosocomial infection caused by A . baumannii resistant to imipenem have reached the proportions of a global health emergency [ 52 ]. According to the International Network for the Study and Emergency Prevention of Antimicrobial Resistance [ 61 ], multi-resistant A .…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of Werneria Chromene and Dihydroxyacidissimol from Burkillanthus malaccensis (Ridl.) Swingle

Zulkipli

Mahbub

Fatima

et al. 2022

Plants

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The secondary metabolites of endemic plants from the Rutaceae family, such as Burkillanthusmalaccensis (Ridl.) Swingle from the rainforest of Malaysia, has not been studied. Burkillanthusmalaccensis (Ridl.) Swingle may produce antibacterial and antibiotic-potentiating secondary metabolites. Hexane, chloroform, and methanol extracts of leaves, bark, wood, pericarps, and endocarps were tested against bacteria by broth microdilution assay and their antibiotic-potentiating activities. Chromatographic separations of hexane extracts of seeds were conducted to investigate effective phytochemicals and their antibacterial activities. Molecular docking studies of werneria chromene and dihydroxyacidissiminol against SARS-CoV-2 virus infection were conducted using AutoDock Vina. The methanol extract of bark inhibited the growth of Staphylococcusaureus, Escherichiacoli, and Pseudomonasaeruginosa with the minimum inhibitory concentration of 250, 500, and 250 µg/mL, respectively. The chloroform extract of endocarps potentiated the activity of imipenem against imipenem-resistant Acinetobacterbaumannii. The hexane extract of seeds increased the sensitivity of P. aeruginosa against ciprofloxacin and levofloxacin. The hexane extract of seeds and chloroform extract of endocarps were chromatographed, yielding werneria chromene and dihydroxyacidissiminol. Werneria chromene was bacteriostatic for P.aeruginosa and P.putida, with MIC/MBC values of 1000 > 1000 µg/mL. Dihydroxyacidissiminol showed the predicted binding energies of −8.1, −7.6, −7.0, and −7.5 kcal/mol with cathepsin L, nsp13 helicase, SARS-CoV-2 main protease, and SARS-CoV-2 spike protein receptor-binding domain S-RBD. Burkillanthusmalaccensis (Ridl.) Swingle can be a potential source of natural products with antibiotic-potentiating activity and that are anti-SARS-CoV-2.

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“… 539 Meanwhile, SARS-CoV-2 helicase (nsp13) was another attractive target. 540 Vivek-Ananth et al 541 estimated the docking scores of 10510 drug-like phytochemicals from PubChem to helicase, and the top five compounds were further evaluated by MM/PBSA calculations. In another work, 131 compounds were docked to helicase.…”

Section: Methods and Approachesmentioning

confidence: 99%

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Gao¹,

Wang²,

Chen³

et al. 2022

Chem. Rev.

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Despite tremendous efforts in the past two years, our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus–host interactions, immune response, virulence, transmission, and evolution is still very limited. This limitation calls for further in-depth investigation. Computational studies have become an indispensable component in combating coronavirus disease 2019 (COVID-19) due to their low cost, their efficiency, and the fact that they are free from safety and ethical constraints. Additionally, the mechanism that governs the global evolution and transmission of SARS-CoV-2 cannot be revealed from individual experiments and was discovered by integrating genotyping of massive viral sequences, biophysical modeling of protein–protein interactions, deep mutational data, deep learning, and advanced mathematics. There exists a tsunami of literature on the molecular modeling, simulations, and predictions of SARS-CoV-2 and related developments of drugs, vaccines, antibodies, and diagnostics. To provide readers with a quick update about this literature, we present a comprehensive and systematic methodology-centered review. Aspects such as molecular biophysics, bioinformatics, cheminformatics, machine learning, and mathematics are discussed. This review will be beneficial to researchers who are looking for ways to contribute to SARS-CoV-2 studies and those who are interested in the status of the field.

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Potential phytochemical inhibitors of SARS-CoV-2 helicase Nsp13: a molecular docking and dynamic simulation study

Cited by 33 publications

References 54 publications

Potential COVID-19 Therapies from Computational Repurposing of Drugs and Natural Products against the SARS-CoV-2 Helicase

Potential COVID-19 Therapies from Computational Repurposing of Drugs and Natural Products against the SARS-CoV-2 Helicase

Isolation and Characterization of Werneria Chromene and Dihydroxyacidissimol from Burkillanthus malaccensis (Ridl.) Swingle

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

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