Amalia Papanikolopoulou, Ilektra Tseliou, Helena C Maltezou
Despite the availability of a safe and effective measles vaccine for several decades, measles remains a significant cause of morbidity and mortality worldwide, causing 95,000 deaths in 2024 alone. Currently, there is no licensed therapeutic agent against measles, and treatment is only supportive. This is a review of articles published from 2015 to 3 June 2025, on therapeutic agents used or under investigation against measles. Ribavirin has been used in severe measles cases; nevertheless, there are no randomized clinical trials so far. New delivery systems, such as polymer-based formulations and nanoparticles, have markedly increased ribavirin's efficacy, while cytotoxicity remained low. Viral membrane fusion (F) protein inhibitors and viral RNA polymerase inhibitors are promising next-generation therapeutics against measles and have been tested in animal models with good results. Lastly, interferons (IFNs) are key mediators of the innate immune response against measles, particularly for controlling brain infection. There are few reports indicating that repeated remdesivir courses, as well as intraventricular or intrathecal ribavirin or IFN, may temporarily stabilize the neurologic status of patients with subacute sclerosing panencephalitis. Intracranial administration of protein F inhibitors also demonstrated promising results in mice. Although several antiviral agents and natural products exhibit in vitro efficacy against measles virus, further research is required to determine their safety, pharmacological properties, and clinical efficacy before they can be considered therapeutic options. Overall, the development of antiviral agents against measles has been extremely slow. Therapeutic agents against measles are urgently needed.