Exploring the potent inhibitors and binding modes of phospholipase A2 through in silico investigation

Mahmud, Shafi; Parves, Md. Rimon; Riza, Yasir Mohamed; Sujon, Khaled Mahmud; Ray, Sumanta; Tithi, Fahmida Alam; Zaoti, Zannati Ferdous; Alam, Sanjida; Absar, Nurul

doi:10.1080/07391102.2019.1680440

Cited by 33 publications

(26 citation statements)

References 72 publications

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“…The simulation result was incorporated with the default script of YASARA. Finally, root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), and Hydrogen bonds (H-bonds) were analyzed (Islam et al., 2019 ; Khan et al., 2020 ; Mahmud et al., 2020a, 2020b ). To have more correct result from molecular dynamics simulation, each complex were run thrice (n=3) and average result was used for analysis.…”

Section: Methodsmentioning

confidence: 99%

Screening of phytochemicals as potent inhibitor of 3-chymotrypsin and papain-like proteases of SARS-CoV2: an in silico approach to combat COVID-19

Swargiary

Mahmud

Saleh

2020

Journal of Biomolecular Structure and Dynamics

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COVID-19 and its causative organism SARS-CoV2 that emerged from Wuhan city, China have paralyzed the world. With no clinically approved drugs, the global health system is struggling to find an effective treatment measure. At this crucial juncture, screening of plant-derived compounds may be an effective strategy to combat COVID-19. The present study investigated the binding affinity of phytocompounds with 3-Chymotrypsin-like (3CLpro) and Papain-like proteases (PLpro) of SARS-CoV2 using in-silico techniques. A total of 32 anti-protease phytocompounds were investigated for the binding affinity to the proteins. Docking was performed in Autodock Vina. Pharmacophore descriptors of best ligands were studied using LigandScout. Molecular dynamics (MD) simulation of apo-protein and ligand-bound complexes was carried out in YASARA software. The druglikeness properties of phytocompounds were studied using ADMETlab. Out of 32 phytochemicals, amentoflavone and gallocatechin gallate showed the best binding affinity to 3CLpro (–9.4 kcal/mol) and PLpro (–8.8 kcal/mol). Phytochemicals such as savinin, theaflavin-3,3-digallate, and kazinol-A also showed strong affinity. MD simulation revealed ligand-induced conformational changes in the protein with decreased surface area and higher stability. The RMSD/F of proteins and ligands showed stability of the protein suggesting the effective binding of the ligand in both the proteins. Both amentoflavone and gallocatechin gallate possess promising druglikeness property. The present study thus suggests that Amentoflavone and Gallocatechin gallate may be potential inhibitors of 3CLpro and PLpro proteins and effective drug candidates for SARS-CoV2. However, the findings of in silico study need to be supported by in vivo studies to establish the exact mode of action. Communicated by Ramaswamy H. Sarma

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Section: Methodsmentioning

confidence: 99%

Screening of phytochemicals as potent inhibitor of 3-chymotrypsin and papain-like proteases of SARS-CoV2: an in silico approach to combat COVID-19

Swargiary

Mahmud

Saleh

2020

Journal of Biomolecular Structure and Dynamics

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“…To be a potent drug candidate against biological target, several parameters such as Lipinski rule of five; molecular weight, hydrogen bond donor, hydrogen bond acceptor, must be followed (Mahmud et al., 2019 ). The screened main protease inhibitors have better oral absorption and blood brain barrier permeability which is required for a drug candidate.…”

Section: Resultsmentioning

confidence: 99%

“…(f) PCA of trajectory data (RMSD, Rg and SASA) of all systems. (Mahmud et al, 2019;Talele et al, 2010). Recently, number of virtual screening process based on plant derived compound have been successful to predict the potential blocker of the biological target (Mahmud et al, 2019(Mahmud et al, , 2020.…”

Section: Discussionmentioning

confidence: 99%

“…This combinatorial process allows us to reduce experimental time and cost by narrowing down biological target. Additionally, molecular dynamics, molecular docking, virtual screening have become essential part in computer aided drug design for their reliability and accurate prediction probability (Mahmud et al., 2019 ; Talele et al., 2010 ). Recently, number of virtual screening process based on plant derived compound have been successful to predict the potential blocker of the biological target (Mahmud et al., 2019 , 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Thereafter, the 30% of total compounds from SP, were filtered to XP. Then, only 10% of compounds were kept before going for MM-GBSA rescoring (Chen et al., 2016 ; Mahmud et al., 2019 ). Finally, the best three ligands were selected and those were considered further, to observe their stability and dynamic nature in biological condition.…”

Section: Methodsmentioning

confidence: 99%

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Molecular docking and dynamics study of natural compound for potential inhibition of main protease of SARS-CoV-2

Mahmud

Uddin

Zaman

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Newly emerged SARS-CoV-2 made recent pandemic situations across the globe is accountable for countless unwanted death and insufferable panic associated with co-morbidities among mass people. The scarcity of appropriate medical treatment and no effective vaccine or medicine against SARS-CoV-2 has turned the situation worst. Therefore, in this study, we made a deep literature review to enlist plant-derived natural compounds and considered their binding mechanism with the main protease of SARS-CoV-2 through combinatorial bioinformatics approaches. Among all, a total of 14 compounds were filtered where Carinol, Albanin, Myricetin were had better binding profile than the rest of the compounds with having binding energy of-8.476,-8.036,-8.439 kcal/mol, respectively. Furthermore, MM-GBSA calculations were also considered in this selection process to support docking studies. Besides, 100 ns molecular dynamics simulation endorsed the rigid nature, less conformational variation and binding stiffness. As this study, represents a perfect model for SARS-CoV-2 main protease inhibition through bioinformatics study, these potential drug candidates may assist the researchers to find a superior and effective solution against COVID-19 after future experiments.

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A conserved subunit vaccine designed against SARS-CoV-2 variants showed evidence in neutralizing the virus

Kibria

Faruque

Islam

et al. 2022

Appl Microbiol Biotechnol

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Novel coronavirus (SARS-CoV-2) leads to coronavirus disease 19 (COVID-19), declared as a pandemic that outbreaks within almost 225 countries worldwide. For the time being, numerous mutations have been reported that led to the generation of numerous variants spread more rapidly. This study aims to establish an efficient multi-epitope subunit vaccine that could elicit both T-cell and B-cell responses sufficient to recognize three confirmed surface proteins of the virus. The sequences of the viral surface proteins, e.g., an envelope protein (E), membrane glycoprotein (M), and S1 and S2 domain of spike surface glycoprotein (S), were analyzed by an immunoinformatic approach. Top immunogenic epitopes have been selected based on the assessment of the affinity with MHC class-I and MHC class-II, population coverage, along with conservancy among wild type and new variants of SARS-CoV-2 genomes. Molecular docking and molecular dynamic simulation suggest that the proposed top peptides have the potential to interact with the highest number of both the MHC class I and MHC class II. The epitopes were assembled by the appropriate linkers to form a multi-epitope vaccine. Epitopes used in the vaccine construct are conserved in all the variants evolved till now. This in silico-designed multi-epitope vaccine is highly immunogenic and induces levels of SARS-CoV2-neutralizing antibodies in mice, which is detected by inhibition of cytopathic effect in Vero cell monolayer. Further studies are required to improve its efficiency in the prevention of virus replication in lung tissue, in addition to safety validation as a step for human application to combat SARS-CoV-2 variants. Key points • We discovered five T-cell epitopes from three surface proteins of SARS-CoV-2. • These are conserved in the wild-type virus and variants, e.g., beta, delta, and omicron. • The multi-epitope vaccine can induce IgG in mice that can neutralize the virus. Supplementary Information The online version contains supplementary material available at 10.1007/s00253-022-11988-x.

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Exploring the potent inhibitors and binding modes of phospholipase A2 through in silico investigation

Cited by 33 publications

References 72 publications

Screening of phytochemicals as potent inhibitor of 3-chymotrypsin and papain-like proteases of SARS-CoV2: an in silico approach to combat COVID-19

Screening of phytochemicals as potent inhibitor of 3-chymotrypsin and papain-like proteases of SARS-CoV2: an in silico approach to combat COVID-19

Molecular docking and dynamics study of natural compound for potential inhibition of main protease of SARS-CoV-2

A conserved subunit vaccine designed against SARS-CoV-2 variants showed evidence in neutralizing the virus

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