Exploring drug repurposing for monkeypox virus: A structural and computational approach

The increasing global threat posed by viral infections that are transmitted to humans from animals has intensified interest in emerging pathogens such as monkeypox virus (MPV). This study investigated the potential of drug repurposing as an efficient therapeutic strategy against MPV, focusing on its close genetic relationships with vaccinia and variola viruses.

Due to the structural and evolutionary similarities among these orthopoxviruses, the Food and Drug Administration (FDA)-approved smallpox drug tecovirimat was selected as a reference drug. A descriptive-analytical approach was used to assess the binding energies of 38 FDA-approved drugs from four therapeutic classes. Molecular docking was performed against key target proteins from the genus Orthopoxvirus.

Several compounds exhibited stronger binding energies than the reference drug tecovirimat, indicating their potential repurposing as anti-MPV agents. To further validate the stability and interaction dynamics of the top performing drug-protein complexes, molecular dynamics (MD) simulations were conducted, which supported their potential as viable candidates for future therapeutic development.

These findings provide promising leads for the development of new therapeutic applications, thereby enhancing both the public health response and commercial value of repurposed treatments. MD simulations also supported the stability and feasibility of these promising drug-protein complexes.