Viral complexes made cryo clear

(From left) Assoc Prof Julien Lescar and team members Dr Abbas El Sahili, graduate student Ms Jia Huan and Dr Xinlei Qian. Credit: NTU.

Human metapneumovirus (HMPV) and the closely related respiratory syncytial virus (RSV) can cause severe infections of the upper respiratory tract and the lungs. Particularly susceptible groups include premature babies, infants and older adults, as well as immunocompromised individuals and those with heart and lung disease.

Given that a structural understanding of these viruses may lead to new drug targets, a team of molecular and structural biologists, led by Assoc Prof Julien Lescar of NTU’s School of Biological Sciences and the NTU Institute of Structural Biology, investigated a key component of HMPV’s infection cycle.

During infection, HMPV releases enzymes into host cells, which form enzyme complexes and initiate viral replication and propagation. Using cryo-electron microscopy, the researchers captured high-resolution images of the HMPV enzyme complexes and built 3D computerised models of them. Analysis of the molecular structures revealed key sites of enzyme interaction that appear to be highly specific for the viruses.

Armed with new structural insights, the researchers aim to develop inhibitors that interrupt enzyme complex formation in a broad spectrum of viruses, including HMPV and RSV.

The research “Structure of the human metapneumovirus polymerase phosphoprotein complex” was reported in Nature (2019), DOI:10.1038/s41586-019-1759–1. Watch animated depictions of enzyme complexes on supplementary  videos 1 and 2.

The article appeared first in NTU’s research & innovation magazine Pushing Frontiers (issue #17, August 2020).