Insights into Antiviral Candidates against Oropouche Virus: A Molecular Dynamics Study.

Abstract

The Oropouche virus (OROV), an emerging arbovirus from the Peribunyaviridae family, represents a growing public health concern in Latin America, particularly due to its rapid urban spread and lack of specific treatments. In this study, we employed an integrated computational strategy combining molecular docking and molecular dynamics (MD) simulations to evaluate the potential of HIV protease inhibitors as candidates for repurposing against the Gc glycoprotein of OROV, a critical component in viral fusion and host cell entry. While docking initially ranked Saquinavir as the top binder, subsequent MD simulations revealed that nelfinavir and indinavir exhibited superior performance across multiple criteria, including binding energy, structural stability, center-of-mass distance maintenance, and consistent hydrogen bonding. These findings emphasize the limitations of docking-only approaches and highlight the importance of dynamic and energetic analyses for accurate inhibitor selection. The proposed computational pipeline demonstrates its value in identifying stable, high-affinity ligands and offers a promising route for accelerating drug discovery against neglected viral diseases such as OROV.