Targeting Mpox: From Pharmacological Mechanisms to Next-Generation Therapies

Mpox, a zoonotic Orthopoxvirus, is a growing global health concern with clinical symptoms like smallpox, including fever, lymphadenopathy, and distinctive rashes. The increasing number of cases emphasizes how urgently antivirals and vaccinations are needed. Antiviral options like tecovirimat, cidofovir, and brincidofovir target DNA polymerase and viral assembly but show varying efficacy. Vaccines such as JYNNEOS and ACAM2000 provide cross-protection, while advancements in mRNA vaccines and recombinant viral vectors offer future promise. Mpox replicates its genome via DNA-dependent RNA polymerase, using envelope proteins for cell entry and evading immune responses through interferon signalling disruption and NF-κB activation. Challenges remain in improving animal models, addressing drug resistance, and ensuring equitable vaccine access. Bioinformatics-driven vaccine design and computational drug repurposing offer rapid solutions for Mpox. PoxApp, a mobile app for symptom tracking and AI analysis, and MPXV-CNN, a model for detecting Mpox image lesions, will accelerate diagnosis and monitoring. Strong pharmacovigilance, innovative treatments, and global collaboration are key to combating Mpox and improving public health resilience.