Sensing the interactions between carbohydrate-binding agents and <i>N</i>-linked glycans of SARS-CoV-2 spike glycoprotein using molecular docking and simulation studies

Lokhande, Kiran Bharat; Apte, Girish R.; Shrivastava, Ashish; Singh, Ashutosh; Pal, Jayanta K.; Swamy, K. Venkateswara; Gupta, Rajesh Kumar

doi:10.1080/07391102.2020.1851303

Cited by 39 publications

(40 citation statements)

References 36 publications

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“…The first three proteins are embedded in a lipid bilayer, while the N protein coats the single-stranded positive-sense viral RNA (Jin et al 2020 ). E protein plays a vital role in the virus assembly (Gupta et al 2020 ), whereas M protein is the most abundant protein that is considered as a central organizer for coronavirus assembly (Boopathi et al 2020 ). The N protein plays an important role in virus transcription and translation (Boopathi et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Flavonoids are promising safe therapy against COVID-19

et al. 2021

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Flavonoids are a class of phenolic natural products, well-identified in traditional and modern medicines in the treatment of several diseases including viral infection. Flavonoids showed potential inhibitory activity against coronaviruses including the current pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and designated as COVID-19. Here, we have collected all data related to the potential inhibitory mechanisms of flavonoids against SARS-CoV-2 infection and their significant immunomodulatory activities. The data were mapped and compared to elect major flavonoids with a promising role in the current pandemic. Further, we have linked the global existence of flavonoids in medicinal plants and their role in protection against COVID-19. Computational analysis predicted that flavonoids can exhibit potential inhibitory activity against SARS-CoV-2 by binding to essential viral targets required in virus entry and/ or replication. Flavonoids also showed excellent immunomodulatory and anti-inflammatory activities including the inhibition of various inflammatory cytokines. Further, flavonoids showed significant ability to reduce the exacerbation of COVID-19 in the case of obesity via promoting lipids metabolism. Moreover, flavonoids exhibit a high safety profile, suitable bioavailability, and no significant adverse effects. For instance, plants rich in flavonoids are globally distributed and can offer great protection from COVID-19. The data described in this study strongly highlighted that flavonoids particularly quercetin and luteolin can exhibit promising multi-target activity against SARS-CoV-2, which promote their use in the current and expected future outbreaks. Therefore, a regimen of flavonoid-rich plants can be recommended to supplement a sufficient amount of flavonoids for the protection and treatment from SARS-CoV-2 infection.

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Section: Introductionmentioning

confidence: 99%

Flavonoids are promising safe therapy against COVID-19

et al. 2021

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“…The urgency of novel drugs for controlling SARS-CoV-2 generates high demand for computational drug discovery approaches. Virtual screening of natural compounds may provide an alternative approach to identify the potential drug candidate to combat pandemic infectious diseases like novel coronavirus disease, particularly where specific FDA-approved drugs are not available [ 1 , 21 , 22 ]. These approaches offer a great opportunity of testing the hypothesis of potential drug effect of the natural compounds like the other synthetic counterparts.…”

Section: Introductionmentioning

confidence: 99%

Identification of potential plant-based inhibitor against viral proteases of SARS-CoV-2 through molecular docking, MM-PBSA binding energy calculations and molecular dynamics simulation

Gogoi¹,

Chowdhury

Goswami

et al. 2021

Mol Divers

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Graphic abstract The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, SARS-CoV-2, has recently emerged as a pandemic. Here, an attempt has been made through in-silico high throughput screening to explore the antiviral compounds from traditionally used plants for antiviral treatments in India namely, Tea, Neem and Turmeric, as potential inhibitors of two widely studied viral proteases, main protease (Mpro) and papain-like protease (PLpro) of the SARS-CoV-2. Molecular docking study using BIOVIA Discovery Studio 2018 revealed, (−)-epicatechin-3-O-gallate (ECG), a tea polyphenol has a binding affinity toward both the selected receptors, with the lowest CDocker energy − 46.22 kcal mol −1 for SARS-CoV-2 Mpro and CDocker energy − 44.72 kcal mol −1 for SARS-CoV-2 PLpro, respectively. The SARS-CoV-2 Mpro complexed with (−)-epicatechin-3-O-gallate, which had shown the best binding affinity was subjected to molecular dynamics simulations to validate its binding affinity, during which, the root-mean-square-deviation values of SARS-CoV-2 Mpro–Co-crystal ligand (N3) and SARS-CoV-2 Mpro- (−)-epicatechin-3-O-gallate systems were found to be more stable than SARS-CoV-2 Mpro system. Further, (−)-epicatechin-3-O-gallate was subjected to QSAR analysis which predicted IC 50 of 0.3281 nM against SARS-CoV-2 Mpro. Overall, (−)-epicatechin-3-O-gallate showed a potential binding affinity with SARS-CoV-2 Mpro and could be proposed as a potential natural compound for COVID-19 treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s11030-021-10211-9.

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“…Earlier, MD has been successful in the discovery of a novel cryptic binding trench in HIV integrase enzyme 48 that eventually led to the development of novel anti-HIV inhibitors such as raltegravir. Recently, MD methods have been extensively used to understand the structures and ligand interactions of SARS-CoV-2 targets including RdRp 30 , 49 – 51 , M pro 18 , 28 , 35 , 38 , 39 , 52 – 54 , and S protein 32 , and computational design of peptide-based subunit vaccines 31 . Therefore, in this work, we use MD to characterize the dynamic interactions of almost all the crystal structures released as of June 10th, 2020 in PDB (the list is provided in the supplementary Table, ST1 ).…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics and in silico mutagenesis on the reversible inhibitor-bound SARS-CoV-2 main protease complexes reveal the role of lateral pocket in enhancing the ligand affinity

Weng

Naik

Dingelstad

et al. 2021

Sci Rep

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The 2019 novel coronavirus pandemic caused by SARS-CoV-2 remains a serious health threat to humans and there is an urgent need to develop therapeutics against this deadly virus. Recent scientific evidences have suggested that the main protease (Mpro) enzyme in SARS-CoV-2 can be an ideal drug target due to its crucial role in the viral replication and transcription processes. Therefore, there are ongoing research efforts to identify drug candidates against SARS-CoV-2 Mpro that resulted in hundreds of X-ray crystal structures of ligand-bound Mpro complexes in the Protein Data Bank (PDB) describing the interactions of different fragment chemotypes within different sites of the Mpro. In this work, we performed rigorous molecular dynamics (MD) simulation of 62 reversible ligand–Mpro complexes in the PDB to gain mechanistic insights about their interactions at the atomic level. Using a total of over 3 µs long MD trajectories, we characterized different pockets in the apo Mpro structure, and analyzed the dynamic interactions and binding affinity of ligands within those pockets. Our results identified the key residues that stabilize the ligands in the catalytic sites and other pockets of Mpro. Our analyses unraveled the role of a lateral pocket in the catalytic site in Mpro that is critical for enhancing the ligand binding to the enzyme. We also highlighted the important contribution from HIS163 in the lateral pocket towards ligand binding and affinity against Mpro through computational mutation analyses. Further, we revealed the effects of explicit water molecules and Mpro dimerization in the ligand association with the target. Thus, comprehensive molecular-level insights gained from this work can be useful to identify or design potent small molecule inhibitors against SARS-CoV-2 Mpro.

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Sensing the interactions between carbohydrate-binding agents and N-linked glycans of SARS-CoV-2 spike glycoprotein using molecular docking and simulation studies

Cited by 39 publications

References 36 publications

Flavonoids are promising safe therapy against COVID-19

Flavonoids are promising safe therapy against COVID-19

Identification of potential plant-based inhibitor against viral proteases of SARS-CoV-2 through molecular docking, MM-PBSA binding energy calculations and molecular dynamics simulation

Molecular dynamics and in silico mutagenesis on the reversible inhibitor-bound SARS-CoV-2 main protease complexes reveal the role of lateral pocket in enhancing the ligand affinity

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