Tepotinib and tivantinib as potential inhibitors for the serine/threonine kinase of the mpox virus: insights from structural bioinformatics analysis

Abduljalil, Jameel M.; Elfiky, Abdo A.; AlKhazindar, Maha M.

doi:10.1080/07391102.2024.2323699

Cited by 2 publications

(1 citation statement)

References 54 publications

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“…It works by blocking the action of an abnormal protein that signals cancer cells to multiply [93][94][95]. As with an in silico approach, tepotinib was screened as a Mpox virus inhibitor based on binding free energy and conformational behavior analysis [96]. Similarly, this study identified two phytochemicals, rhein and taxifolin, as promising compounds with drug-like properties for inhibiting the macro domain of the chikungunya virus [97,98].…”

Section: Discussionmentioning

confidence: 99%

Potential Inhibitors of Lumpy Skin Disease’s Viral Protein (DNA Polymerase): A Combination of Bioinformatics Approaches

Zia,

Sumon,

Ashik

et al. 2024

Animals

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Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle. This spreads through direct contact and insect vectors, significantly affecting global cattle farming. Despite the availability of vaccines, their efficacy is limited by poor prophylaxis and adverse effects. Our study aimed to identify the potential inhibitors targeting the LSDV-encoded DNA polymerase protein (gene LSDV039) for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as being potent binders among 380 phytocompounds, with respective affinities of −8.97 and −7.20 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (−9.86 and −8.86 kcal/mol) among 718 FDA-approved antiviral drugs. Simulating the molecular dynamics of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin’s superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF, but fluctuated in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. This study highlights the promising potential of using repurposed drugs and phytocompounds as potential LSD therapeutics. However, extensive validation through in vitro and in vivo testing and clinical trials is crucial for their practical application.

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Section: Discussionmentioning

confidence: 99%

Potential Inhibitors of Lumpy Skin Disease’s Viral Protein (DNA Polymerase): A Combination of Bioinformatics Approaches

Zia,

Sumon,

Ashik

et al. 2024

Animals

View full text Add to dashboard Cite

show abstract

Potential Inhibitors of Lumpy Skin Disease’s Viral Protein (DNA Polymerase): A Combination of Bioinformatics Approaches

Zia,

Sumon,

Ashik

et al. 2024

Preprint

View full text Add to dashboard Cite

Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle, spreading through direct contact and insect vectors, significantly affecting global cattle farming. Despite available vaccines, their effectiveness is limited by poor bioavailability and adverse effects. Our study aimed to identify potential inhibitors targeting LSD-associated DNA polymerase protein, selecting LSDV039 for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as potent binders among 380 phytocompounds, with respective affinities of -8.965 and -7.195 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (-9.858 and -8.856 kcal/mol) among 718 FDA-approved antiviral drugs. Molecular dynamics simulations of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin's superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF but fluctuations in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. The study highlights the promising potential of repurposed drugs and phytocompounds as LSD therapeutics. However, extensive validation through in-vitro, in-vivo, and clinical trials is crucial for their practical application.

show abstract

Tepotinib and tivantinib as potential inhibitors for the serine/threonine kinase of the mpox virus: insights from structural bioinformatics analysis

Cited by 2 publications

References 54 publications

Potential Inhibitors of Lumpy Skin Disease’s Viral Protein (DNA Polymerase): A Combination of Bioinformatics Approaches

Potential Inhibitors of Lumpy Skin Disease’s Viral Protein (DNA Polymerase): A Combination of Bioinformatics Approaches

Potential Inhibitors of Lumpy Skin Disease’s Viral Protein (DNA Polymerase): A Combination of Bioinformatics Approaches

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