A computerized pharmaceutical repurposing approach reveals Semicochliodinol B synthesized from Chrysosporium merdarium as a viable therapeutic contender for Marburg virus's VP35 and VP40 proteins

Hasan, Mahamudul; Mia, Md. Mukthar; Islam, Md. Mazharul; Saraf, Md. Sawkat Hasan; Islam, Md. Shariful

doi:10.1016/j.imu.2021.100821

Cited by 5 publications

(3 citation statements)

References 51 publications

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“…This is especially relevant considering the limited number of studies focusing on marine-derived compounds for MBV inhibition, highlighting the novelty and potential impact of our work. Comparatively, our results demonstrate advancements over existing studies by showcasing not only the binding affinities but also the dynamic stability of these compounds within the VP35 protein environment [16][17][18]28]. This comprehensive analysis bridges the gap between static structural insights and dynamic molecular behavior, offering a more holistic view of potential drug efficacy.…”

Section: Discussionsupporting

confidence: 53%

“…Although recent reports have highlighted MBV VP35 inhibitors like Semicochliodinol B, Stigmasterol, and Estradiol Benzoate, there is a desperate need for further research in this area [16][17][18]. The complexity and variability of the MBV suggest that a wider array of inhibitors from different sources could be beneficial in developing more effective treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

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Structural and Dynamical Basis of VP35-RBD Inhibition by Marine Fungi Compounds to Combat Marburg Virus Infection

Alawam,

Alshahrani

et al. 2024

Marine Drugs

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The Marburg virus (MBV), a deadly pathogen, poses a serious threat to world health due to the lack of effective treatments, calling for an immediate search for targeted and efficient treatments. In this study, we focused on compounds originating from marine fungi in order to identify possible inhibitory compounds against the Marburg virus (MBV) VP35-RNA binding domain (VP35-RBD) using a computational approach. We started with a virtual screening procedure using the Lipinski filter as a guide. Based on their docking scores, 42 potential candidates were found. Four of these compounds—CMNPD17596, CMNPD22144, CMNPD25994, and CMNPD17598—as well as myricetin, the control compound, were chosen for re-docking analysis. Re-docking revealed that these particular compounds had a higher affinity for MBV VP35-RBD in comparison to the control. Analyzing the chemical interactions revealed unique binding properties for every compound, identified by a range of Pi–cation interactions and hydrogen bond types. We were able to learn more about the dynamic behaviors and stability of the protein–ligand complexes through a 200-nanosecond molecular dynamics simulation, as demonstrated by the compounds’ consistent RMSD and RMSF values. The multidimensional nature of the data was clarified by the application of principal component analysis, which suggested stable conformations in the complexes with little modification. Further insight into the energy profiles and stability states of these complexes was also obtained by an examination of the free energy landscape. Our findings underscore the effectiveness of computational strategies in identifying and analyzing potential inhibitors for MBV VP35-RBD, offering promising paths for further experimental investigations and possible therapeutic development against the MBV.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Structural and Dynamical Basis of VP35-RBD Inhibition by Marine Fungi Compounds to Combat Marburg Virus Infection

Alawam,

Alshahrani

et al. 2024

Marine Drugs

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“…This binding also masks VP35 from host factors and likely prevents its degradation [ 17 , 18 , 19 , 20 , 21 ]. Additionally, various studies have shown that VP35 can be used as a potential drug target for MARV as it is effective in Ebola infection treatment [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Cheminformatics Strategies Unlock Marburg Virus VP35 Inhibitors from Natural Compound Library

Alsaady,

Bajrai,

Alandijany

et al. 2023

Viruses

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The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae and are highly hazardous and contagious viruses. With a mortality rate ranging from 23% to 90%, depending on the specific outbreak, the development of effective antiviral interventions is crucial for reducing fatalities and mitigating the impact of Marburg virus outbreaks. In this investigation, a virtual screening approach was employed to evaluate 2042 natural compounds for their potential interactions with the VP35 protein of the Marburg virus. Average and worst binding energies were calculated for all 20 poses, and compounds that exhibited binding energies <−6 kcal/mol in both criteria were selected for further analysis. Based on binding energies, only six compounds (Estradiol benzoate, INVEGA (paliperidone), Isosilybin, Protopanaxadiol, Permethrin, and Bufalin) were selected for subsequent investigations, focusing on interaction analysis. Among these selected compounds, Estradiol benzoate, INVEGA (paliperidone), and Isosilybin showed strong hydrogen bonds, while the others did not. In this study, the compounds Myricetin, Isosilybin, and Estradiol benzoate were subjected to a molecular dynamics (MD) simulation and free binding energy calculation using MM/GBSA analysis. The reference component Myricetin served as a control. Estradiol benzoate exhibited the most stable and consistent root-mean-square deviation (RMSD) values, whereas Isosilybin showed significant fluctuations in RMSD. The compound Estradiol benzoate exhibited the lowest ΔG binding free energy (−22.89 kcal/mol), surpassing the control compound’s binding energy (−9.29 kcal/mol). Overall, this investigation suggested that Estradiol benzoate possesses favorable binding free energies, indicating a potential inhibitory mechanism against the VP35 protein of the Marburg virus. The study proposes that these natural compounds could serve as a therapeutic option for preventing Marburg virus infection. However, experimental validation is required to further corroborate these findings.

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Molecular modelling and simulation techniques to investigate the effects of fungal metabolites on the SARS-CoV-2 RdRp protein inhibition

Muddapur

Badiger

Shaikh

et al. 2022

Journal of King Saud University - Science

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A computerized pharmaceutical repurposing approach reveals Semicochliodinol B synthesized from Chrysosporium merdarium as a viable therapeutic contender for Marburg virus's VP35 and VP40 proteins

Cited by 5 publications

References 51 publications

Structural and Dynamical Basis of VP35-RBD Inhibition by Marine Fungi Compounds to Combat Marburg Virus Infection

Structural and Dynamical Basis of VP35-RBD Inhibition by Marine Fungi Compounds to Combat Marburg Virus Infection

Cheminformatics Strategies Unlock Marburg Virus VP35 Inhibitors from Natural Compound Library

Molecular modelling and simulation techniques to investigate the effects of fungal metabolites on the SARS-CoV-2 RdRp protein inhibition

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