Computational
approaches revealing potential anti-HMPV therapeutic candidates
Quan Ke Thai, Phuoc Huynh and Hien Pham Thi Thanh
Res. J. Biotech.; Vol. 21(1); 1-11;
doi: https://doi.org/10.25303/211rjbt01011; (2026)
Abstract
Human metapneumovirus (HMPV) has emerged as a significant respiratory pathogen with
substantial clinical and public health implications. Despite its widespread circulation
in many countries, no specific antiviral drugs or vaccines have been approved for
HMPV treatment. Therefore, identifying repurposed drugs with potential efficacy
against HMPV represents a rational strategy to accelerate drug development. In this
study, we employed 2,118 molecules of the e-Drug3D library comprising of FDA-approved
drugs to the HMPV CR-VI protein structure (MTase). This protein plays a crucial
role in viral RNA synthesis by catalyzing the methylation of the RNA cap at the
2′O and N7 positions. Our virtual screening results identified the antiviral agents
PIBRENTASVIR, ELBASVIR, RITONAVIR and REMDESIVIR as high-affinity binders to MTase
through interactions with its catalytic sites, SAMP and SUBP. Molecular dynamics
simulations demonstrated that PIBRENTASVIR, RITONAVIR and REMDESIVIR form stable
interactions within the MTase binding pocket.
Furthermore, binding free energy analysis revealed strong binding affinities and
competitive interactions with the MTase active site, particularly with GTP. This
study provides the evidence of these molecules as potential MTase inhibitors. Our
findings establish an initial framework for further screening and clinical evaluation,
contributing to the development of effective anti-HMPV therapeutics.
