Artesunate repurposing for cytomegalovirus management: a systematic review of efficacy, mechanisms, and perspectives.

BACKGROUND

Cytomegalovirus (CMV) is a prevalent opportunistic pathogen associated with significant morbidity and mortality in immunocompromised individuals, particularly transplant recipients and neonates. Current antiviral therapies are often constrained by substantial toxicity and the emergence of drug resistance. Artesunate (ART), a proven antimalarial agent with established safety profiles, has been explored for potential repurposing against CMV infection, though its anti-CMV pharmacodynamics remain incompletely elucidated.

METHODS

This systematic review synthesized evidence from 46 studies published through December 2025, covering in vitro, in vivo, and clinical studies, to evaluate the efficacy, mechanisms of action, and translational challenges of ART-based anti-CMV strategies.

RESULTS

ART exhibits potent anti-CMV activity in vitro, with no reported cross-resistance to conventional antiviral agents. Structure-activity relationship analysis indicates that the endoperoxide bridge and hemisuccinate side chain may contribute to its antiviral effects. While optimized ART derivatives show improved potency, they remain in the preclinical research stage. Clinical evidence for ART is limited, primarily derived from small-scale and combination therapy studies, with inconsistent outcomes typically marked by an initial reduction in viral load rather than sustained complete clearance. Mechanistically, ART may exert anti-CMV effects through multiple host-regulated pathways, including NF-κB inhibition, G0/G1 cell cycle arrest, and modulation of mitochondrial dynamics.

CONCLUSIONS

The short plasma half-life of ART may represent a pharmacokinetic limitation to its clinical application. Further research, including formulation optimization, targeted pharmacokinetic/pharmacodynamic studies, and well-controlled clinical trials, is warranted to evaluate the potential role of ART in CMV management.