Mapping and characterization of G-quadruplexes in monkeypox genomes

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dc.contributor.authorPereira, Higor S.
dc.contributor.authorGemmill, Darren L.
dc.contributor.authorSiddiqui, M. Quadir
dc.contributor.authorVasudeva, Gujuan
dc.contributor.authorPatel, Trushar R.
dc.date.accessioned2024-06-12T22:58:47Z
dc.date.available2024-06-12T22:58:47Z
dc.date.issued2022
dc.descriptionOpen access article. Creative Commons Attribution-NonCommercial 4.0 International license (CC BY-NC 4.0) applies
dc.description.abstractMonkeypox virus (MPXV) is a double-stranded DNA virus from the family Poxviridae, which is endemic in West and Central Africa. Various human outbreaks occurred in the 1980s, resulting from a cessation of smallpox vaccination. Recently, MPXV cases have reemerged in non-endemic nations, and the 2022 outbreak has been declared a public health emergency. Treatment optionsare limited, and many countries lack the infrastructure to provide symptomatic treatments. The development of cost-effective antivirals could ease severe health outcomes. G-quadruplexes have been a target of interest in treating viral infections with different chemicals. In the present work, a genomic-scale mapping of different MPXV isolates highlighted two conserved putative quadruplex-forming sequences MPXV-exclusive in 590 isolates. Subsequently, we assessed the G-quadruplex formation using circular dichroism spectroscopy and solution small-angle X-ray scattering. Furthermore, biochemical assays indicated the ability of MPXV quadruplexes to be recognized by two specific G4-binding partners—Thioflavin T and DHX36. Additionally, our work also suggests that a quadruplex binding small-molecule with previously reported antiviral activity, TMPyP4, interacts with MPXV G-quadruplexes with nanomolar affinity in the presence and absence of DHX36. Finally, cell biology experiments suggests that TMPyP4 treatment substantially reduced gene expression of MPXV proteins. In summary, our work provides insights into the G-quadruplexes from the MPXV genome that can be further exploited to develop therapeutics.
dc.identifier.citationPereira, H. S., Gemmill, D. L., Siddiqui, M. Q., Vasudeva, G., & Patel, T. R. (2022). Mapping and characteristics of G-quadruplexes in monkeypox genomes. Journal of Medical Virology, 95(5), Article e28783. https://doi.org/10.1002/jmv.28783
dc.identifier.urihttps://hdl.handle.net/10133/6781
dc.language.isoen
dc.publisherWiley
dc.publisher.departmentDepartment of Chemistry and Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionUniversity of Lethbridge
dc.publisher.institutionUniversity of Calgary
dc.publisher.institutionUniversity of Alberta
dc.subjectGenomic mapping
dc.subjectG-quadruplexes
dc.subjectMonkeypox
dc.subjectPoxvirus
dc.subjectSAXS
dc.subjectTMPyP4
dc.subject.lcshQuadruplex nucleic acids
dc.subject.lcshPoxvirus diseases
dc.titleMapping and characterization of G-quadruplexes in monkeypox genomes
dc.typeArticle
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