Exploration of drug repurposing for Mpox outbreaks targeting gene signatures and host-pathogen interactions DOI Creative Commons
Saber İmani, Sargol Aminnezhad,

Moslem Alikarami

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 27, 2024

Monkeypox (Mpox) is a growing public health concern, with complex interactions within host systems contributing to its impact. This study employs multi-omics approaches uncover therapeutic targets and potential drug repurposing opportunities better understand Mpox's molecular pathogenesis. We developed an in silico host-pathogen interaction (HPI) network applied weighted gene co-expression analysis (WGCNA) explore between Mpox proteins. Subtype-specific protein-protein networks were constructed, key modules from the HPI WGCNA integrated identify significant To predict upstream signaling pathways transcription factors, we used eXpression2Kinases ChIP-X Enrichment Analysis. The multi-Steiner trees method was compare our findings those FDA-approved antiviral drugs. Analysis of 55 differentially expressed genes infection revealed 11 kinases 15 factors as regulators. identified 16 targets, categorized into 8 proviral (ESR2, ERK1, ERK2, P38, JNK1, CDK4, GSK3B, STAT3) designated for inhibition, (IKKA, HDAC1, HIPK2, TF65, CSK21, ESR2, GSK3B) activation. Proviral are involved AKT, Wnt, STAT3 pathways, while impact AP-1, NF-κB, apoptosis, IFN pathways. Promising candidates identified, including kinase inhibitors, steroid hormone receptor agonists, notably Niclosamide. enhances understanding by identifying repurposable drugs, providing valuable framework developing new treatments.

Language: Английский

An overview on monkeypox virus: Pathogenesis, transmission, host interaction and therapeutics DOI Creative Commons
Shailima Rampogu,

Yong‐Seong Kim,

Seon-Won Kim

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Feb. 10, 2023

Orthopoxvirus is one of the most notorious genus amongst Poxviridae family. Monkeypox (MP) a zoonotic disease that has been spreading throughout Africa. The spread global, and incidence rates are increasing daily. virus rapid due to human-to-human animals-to-human transmission. World Health Organization (WHO) declared monkeypox (MPV) as global health emergency. Since treatment options limited, it essential know modes transmission symptoms stop spread. information from host–virus interactions revealed significantly expressed genes important for progression MP infection. In this review, we highlighted structure, modes, available therapeutic options. Furthermore, review provides insights scientific community extend their research work in field.

Language: Английский

Citations

28
A Review of the Molecular Understanding of the Mpox Virus (MPXV): Genomics, Immune Evasion, and Therapeutic Targets DOI Creative Commons
Edgar Cambaza

Zoonotic Diseases, Journal Year: 2025, Volume and Issue: 5(1), P. 3 - 3

Published: Jan. 16, 2025

The Mpox virus (MPXV), a zoonotic pathogen from the Orthopoxvirus genus, has emerged as significant global public health concern, especially after unprecedented outbreak in 2022. This review synthesizes MPXV’s molecular features, focusing on its genomic structure, replication mechanisms, immune evasion strategies, and implications for diagnostics therapeutics. study examines virus’s organization utilizing recent peer-reviewed literature, highlighting essential genes like OPG027 D1L, which contribute to host adaptation, increased transmissibility, evasion. Advances diagnostics, including real-time PCR genome sequencing, are reviewed, emphasizing their critical role monitoring control. However, challenges persist, such diagnostic limitations resource-constrained settings lack of targeted vaccines antivirals. discusses new antiviral candidates, confirmed through computational vitro techniques, identifying thymidine kinase VP39 key therapeutic targets. Emphasizing need surveillance track adaptive evolution, results show that particular mutations, D1L genes, increase transmissibility MPXV. These revelations highlight urgent necessity better catered towards addressing present constraints developing focused treatments reduce effect virus. emphasizes how these underscore combined plans handle changing MPXV epidemiology properly.

Language: Английский

Citations

1
Current trends in diagnostics, biomarker identification, and drug discovery targeting Monkeypox (Mpox) DOI Creative Commons
Pervej Alom Barbhuiya, M. A. Laskar, Sudip Talukdar

et al.

The Microbe, Journal Year: 2025, Volume and Issue: unknown, P. 100330 - 100330

Published: April 1, 2025

Language: Английский

Citations

0
In-silico discovery of type-2 diabetes-causing host key genes that are associated with the complexity of monkeypox and repurposing common drugs DOI Creative Commons

Alvira Ajadee,

Sabkat Mahmud,

Md. Ahad Ali

et al.

Briefings in Bioinformatics, Journal Year: 2025, Volume and Issue: 26(3)

Published: May 1, 2025

Abstract Monkeypox (Mpox) is a major global human health threat after COVID-19. Its treatment becomes complicated with type-2 diabetes (T2D). It may happen due to the influence of both disease-causing common host key genes (cHKGs). Therefore, it necessary explore cHKGs reveal their shared pathogenetic mechanisms and candidate drugs as treatments without adverse side effect. This study aimed address these issues. At first, 3 transcriptomics datasets for each Mpox 6 T2D were analyzed found 52 differentially expressed (cHDEGs) that can separate patients from control samples. Then top-ranked six cHDEGs (HSP90AA1, B2M, IGF1R, ALD1HA1, ASS1, HADHA) detected T2D-causing are associated complexity through protein–protein interaction network analysis. processes between disclosed by cHKG-set enrichment analysis biological processes, molecular functions, cellular components Kyoto Encyclopedia Genes Genomes pathways, regulatory transcription factors microRNAs. Finally, cHKG-guided three drug molecules (tecovirimat, vindoline, brincidofovir) recommended repurposable therapeutic agents docking. The absorption, distribution, metabolism, excretion, toxicity drug-likeness indicated good pharmacokinetics properties. 100-ns dynamics simulation results (root mean square deviation, root fluctuation, mechanics generalized born surface area) complexes ASS1-tecovirimat, ALDH1A1-vindoline, B2M-brincidofovir exhibited pharmacodynamics provided in this article might be important resources diagnosis therapies who also suffering T2D.

Language: Английский

Citations

0
Exploration of drug repurposing for Mpox outbreaks targeting gene signatures and host-pathogen interactions DOI Creative Commons
Saber İmani, Sargol Aminnezhad,

Moslem Alikarami

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 27, 2024

Monkeypox (Mpox) is a growing public health concern, with complex interactions within host systems contributing to its impact. This study employs multi-omics approaches uncover therapeutic targets and potential drug repurposing opportunities better understand Mpox's molecular pathogenesis. We developed an in silico host-pathogen interaction (HPI) network applied weighted gene co-expression analysis (WGCNA) explore between Mpox proteins. Subtype-specific protein-protein networks were constructed, key modules from the HPI WGCNA integrated identify significant To predict upstream signaling pathways transcription factors, we used eXpression2Kinases ChIP-X Enrichment Analysis. The multi-Steiner trees method was compare our findings those FDA-approved antiviral drugs. Analysis of 55 differentially expressed genes infection revealed 11 kinases 15 factors as regulators. identified 16 targets, categorized into 8 proviral (ESR2, ERK1, ERK2, P38, JNK1, CDK4, GSK3B, STAT3) designated for inhibition, (IKKA, HDAC1, HIPK2, TF65, CSK21, ESR2, GSK3B) activation. Proviral are involved AKT, Wnt, STAT3 pathways, while impact AP-1, NF-κB, apoptosis, IFN pathways. Promising candidates identified, including kinase inhibitors, steroid hormone receptor agonists, notably Niclosamide. enhances understanding by identifying repurposable drugs, providing valuable framework developing new treatments.

Language: Английский

Citations

1