Computational screening of FDA-approved and natural compounds against Mpox Dual specificity protein phosphatase (H1)

Abstract

The resurgence of mpox as a global public health issue emphasizes the urgent need for innovative treatment approaches. Mpox dual specificity protein phosphatase (H1) is an interesting anti-poxvirus therapeutic target due to its role in controlling interferon signaling and viral replication. Inhibiting the operation of Mpox H1 would prevent the virus from multiplying and hence aid in disease management. Leveraging the repurposing potential of FDA-approved drugs and natural products, this study screened two compound libraries for their ability to bind Mpox H1. The docking scores were compared to a standard compound, NSC-62914, a compound known to inhibit the dual-specificity H1 phosphatase of Variola major virus. The top scoring complexes were further processed using MD simulations. Among the tested compounds, DB00358 from the FDA-approved library and TN1406 from the natural products library respectively were identified with the highest binding affinity and better stability. Given the effectiveness of NSC-62914 against a homologous dual-specificity H1 phosphatase in the Variola major virus, it is also proposed as a potential inhibitor for Mpox H1. These findings based on computational analysis could lead to the development of new potential antiviral treatments to combat Mpox, contributing to global efforts against this emerging infectious disease.