Antiviral Candidates and Vaccine Development for the Neglected Oropouche Virus

The Oropouche virus (OROV), an orthobunyavirus primarily transmitted by the biting midge Culicoides paraensis, is the causative agent of Oropouche fever, a re-emerging arboviral disease associated with significant morbidity in Central and South America. The increasing frequency of outbreaks, including cases of sustained transmission in non-endemic regions and reports of vertical transmission, highlights the growing public health concern posed by OROV. Currently, there are no specific antiviral therapies or licensed vaccines available, underscoring the urgent need for effective therapeutic and preventive strategies. Recent advances in antiviral research have identified promising candidates, including repurposed drugs and bioactive compounds that target key stages of the viral replication cycle. In parallel, vaccine development has progressed through modern platforms, including viral vector-based and nucleic-acid-based technologies, enabling rapid responses to emerging outbreaks. However, major challenges remain, particularly due to the limited understanding of OROV pathogenesis, virus-host interactions, and the correlates of protective immunity. Furthermore, the ongoing evolution of OROV, including the genetic diversity and potential genomic rearrangements observed among circulating strains, represents an additional challenge that may influence viral characteristics and potentially affect the long-term efficacy of antiviral interventions and vaccine-induced protection. This review summarizes recent advances in the discovery of antiviral candidates and the development of vaccine approaches against OROV, both of which are essential for reducing the impact of OROV infections and strengthening preparedness for future outbreaks.