Potential of Acyclovir, Allopurinol and B Vitamins for the Treatment of Mpox Viral Infection; Insight from Molecular Docking of the Mpox Virus Multi-Domain DNA Polymerase
Year: 2025
Type: preprint
Abstract: Unpredictable emerging and re-emerging of Mpox virus (MPXV) outbreaks account for urgent interventions. While no drug has been approved for Mpox treatment, repurposing of nucleoside analog drugs such as tecovirimat and cidofovir is the current focus of many intervention initiatives. Intrigued by their molecular structural similarities, we hypothesized that acyclovir, allopurinol, and B vitamins, which structurally resemble tecovirimat and cidofovir, could be competitive inhibitors of the MPXV DNA polymerase, abrogating DNA synthesis viral multiplication. We applied computational molecular docking experiments to investigate this hypothesis. Our results revealed that acyclovir fits exactly into the binding cavity for cidofovir and interacts with the same MPXV DNA polymerase amino acid residues with comparatively similar binding energy. We also found that oxipurinol (a metabolite of allopurinol) expresses higher affinity for MPXV DNA polymerase than cidofovir. Interestingly, the B vitamins riboflavin and folic acid outcompeted cidofovir, acyclovir and deoxyribonucleoside triphosphates (dNTPs), the natural substrates for DNA polymerase. From these ligand-receptor interactions we infer that acyclovir, oxipurinol and B vitamins are competitive inhibitors, targeting the active rather than the allosteric site of MPXV DNA polymerase. Our findings provide a novel insight into the B vitamin’s mode of action, emphasizing their antiviral potential via direct hijacking of the viral DNA replication machinery. While B vitamins are easy to find and cheaper, wet laboratory studies equipped with bioinformatics capacity could validate our findings to drive clinical trials. Once well established, B vitamins can be a cheap and reliable venture for pandemic preparedness for viral outbreaks.
Source: Preprints.org
Language: English
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4409287597