Disclosing pathogenic processes of monkeypox (MPOX) and drug repurposing through host-transcriptomics analysis
6 affiliations
- 1Bioinformatics Lab (Dry), Department of Statistics, University of Rajshahi, Rajshahi, Bangladesh
- 2Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, School of Medicine, Tulane University, New Orleans, Louisiana, United States of America
- 3Department of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, Texas, United States of America
- 4Department of Biochemistry & Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh
- 5Department of Statistics and Data Science, University of Barishal, Barishal, Bangladesh
- 6Department of Computer Science and Engineering, Rajshahi University of Engineering and Technology, Rajshahi, Bangladesh
Abstract
Monkeypox (MPOX) virus infection outbreak in Africa in 2022 was initially considered a neglected tropical disease (NTD). Now it is recognized as a global health problem. The recent global spread has emphasized the need for increased attention to combat MPOX. Although there are some vaccines against MPOX, most people worldwide are still not vaccinated due to their unawareness or unavailability. However, so far, there is no approved drug against MPOX yet. Therefore, effective drugs against MPOX are also essential. This study attempted to disclose pathogenic processes and therapeutic strategies of MPOX based on MPOX-associated host key-genes (hKGs). At first, three transcriptomic profile datasets were analyzed, identifying 166 common host differentially expressed genes (hDEGs) between MPOX patients and control groups, comprising 75 upregulated and 91 downregulated hDEGs. Subsequently, six top-ranked host key genes (hKGs): ALB, HSP90AA1, CDH1, PTPRC, IGF1, and ABL1, were identified as potential MPOX-causing genes through protein-protein interaction (PPI) network analysis. Functional enrichment analysis of these hKGs revealed critical pathogenic processes of MPOX infection, including biological processes, molecular functions, cellular components, and KEGG pathways. Regulatory network analysis involving transcription factors and miRNAs provided further insights into disease mechanisms. Based on molecular docking analysis, five top-ranked drug molecules Tecovirimat, Beclabuvir, Maraviroc, Raltegravir, and Brincidofovir were identified as potential repurposable therapeutics against MPOX. ADME/T and drug-likeness evaluations confirmed favorable pharmacokinetic properties for these candidates. Additionally, 100 ns molecular dynamics (MD) simulations of the top three complexes (ALB-Tecovirimat, CDH1-Maraviroc, and PPARG-Beclabuvir) demonstrated strong binding stability, supported by RMSD, RMSF, and MM-GBSA results. Therefore, the results provided in this study might be potential resources for diagnosis and therapies of MPOX patients. However, the findings require experimental validation in wet lab for further confirmation. Author summary: Monkeypox virus infection has become a one of the global health concerns, after COVID-19. Although vaccines are available, many people still have limited access to the vaccination, and so effective treatments are needed. In antiviral drug discovery, potential targets may include pathogenic viral proteins or host proteins that are dysregulated by the interaction of pathogenic viral proteins. However, viral proteins guided antiviral drugs may become inactive/resistant, since virus RNAs are often modified due to environmental stress. In contrast, host proteins tend to be more stable and less susceptible for such situations, making them attractive alternative targets for antiviral strategies. We therefore identified host key-genes associated with the Monkeypox virus infection through transcriptomics analysis for exploring effective antiviral candidates. We then investigated biological processes, molecular functions, cellular components and pathways that might be associated with infection through the enrichment analysis of key-genes. Finally, key-genes guided five molecules were recommended as the. drug candidate against the infection. However, these findings are based on computational analyses, so laboratory experiments and clinical studies will be necessary to finalize them.
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BibTeX
@article{mahmud2026disclosing,
title = {{Disclosing pathogenic processes of monkeypox (MPOX) and drug repurposing through host-transcriptomics analysis}},
author = {Sabkat Mahmud and Alvira Ajadee and Md. Ahad Ali and Md. Feroj Ahmed and Reaz Ahmmed and Md. Masud Rana and Tasfia Noor and Md. Fahim Faysal and Md. Hadiul Kabir and Md. Nurul Haque Mollah},
journal = {PLOS Neglected Tropical Diseases},
year = {2026},
month = oct,
doi = {10.1371/journal.pntd.0014797},
url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014797},
note = {CC BY},
}
RIS
TY - JOUR
TI - Disclosing pathogenic processes of monkeypox (MPOX) and drug repurposing through host-transcriptomics analysis
AU - Sabkat Mahmud
AU - Alvira Ajadee
AU - Md. Ahad Ali
AU - Md. Feroj Ahmed
AU - Reaz Ahmmed
AU - Md. Masud Rana
AU - Tasfia Noor
AU - Md. Fahim Faysal
AU - Md. Hadiul Kabir
AU - Md. Nurul Haque Mollah
PY - 2026
DA - 2026/10/01
JO - PLOS Neglected Tropical Diseases
DO - 10.1371/journal.pntd.0014797
UR - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014797
AB - Monkeypox (MPOX) virus infection outbreak in Africa in 2022 was initially considered a neglected tropical disease (NTD). Now it is recognized as a global health problem. The recent global spread has emphasized the need for increased attention to combat MPOX. Although there are some vaccines against MPOX, most people worldwide are still not vaccinated due to their unawareness or unavailability. However, so far, there is no approved drug against MPOX yet. Therefore, effective drugs against MPOX are also essential. This study attempted to disclose pathogenic processes and therapeutic strategies of MPOX based on MPOX-associated host key-genes (hKGs). At first, three transcriptomic profile datasets were analyzed, identifying 166 common host differentially expressed genes (hDEGs) between MPOX patients and control groups, comprising 75 upregulated and 91 downregulated hDEGs. Subsequently, six top-ranked host key genes (hKGs): ALB, HSP90AA1, CDH1, PTPRC, IGF1, and ABL1, were identified as potential MPOX-causing genes through protein-protein interaction (PPI) network analysis. Functional enrichment analysis of these hKGs revealed critical pathogenic processes of MPOX infection, including biological processes, molecular functions, cellular components, and KEGG pathways. Regulatory network analysis involving transcription factors and miRNAs provided further insights into disease mechanisms. Based on molecular docking analysis, five top-ranked drug molecules Tecovirimat, Beclabuvir, Maraviroc, Raltegravir, and Brincidofovir were identified as potential repurposable therapeutics against MPOX. ADME/T and drug-likeness evaluations confirmed favorable pharmacokinetic properties for these candidates. Additionally, 100 ns molecular dynamics (MD) simulations of the top three complexes (ALB-Tecovirimat, CDH1-Maraviroc, and PPARG-Beclabuvir) demonstrated strong binding stability, supported by RMSD, RMSF, and MM-GBSA results. Therefore, the results provided in this study might be potential resources for diagnosis and therapies of MPOX patients. However, the findings require experimental validation in wet lab for further confirmation. Author summary: Monkeypox virus infection has become a one of the global health concerns, after COVID-19. Although vaccines are available, many people still have limited access to the vaccination, and so effective treatments are needed. In antiviral drug discovery, potential targets may include pathogenic viral proteins or host proteins that are dysregulated by the interaction of pathogenic viral proteins. However, viral proteins guided antiviral drugs may become inactive/resistant, since virus RNAs are often modified due to environmental stress. In contrast, host proteins tend to be more stable and less susceptible for such situations, making them attractive alternative targets for antiviral strategies. We therefore identified host key-genes associated with the Monkeypox virus infection through transcriptomics analysis for exploring effective antiviral candidates. We then investigated biological processes, molecular functions, cellular components and pathways that might be associated with infection through the enrichment analysis of key-genes. Finally, key-genes guided five molecules were recommended as the. drug candidate against the infection. However, these findings are based on computational analyses, so laboratory experiments and clinical studies will be necessary to finalize them.
SN - 1935-2735
SN - 1935-2727
ER -