3D structure of key pneumonia virus enzyme discovered by NTU scientists
A novel method to disable human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) has been discovered by a team of structural and molecular biologists from Nanyang Technological University, Singapore (NTU Singapore). They developed the method after elucidating the structure of one of its key components.
According to the reports by UNICEF, pneumonia killed a child every 39 seconds in 2018, yet there are no effective vaccines or antivirals available against it.
RSV and HMPV confiscate the cell’s machinery, once they infect the cells to make copies of themselves. The distinct protein complexes formed from the special proteins released by viruses initiate the process.
Dr. Julien Lescar and his team from NTU reported in Nature that they used cryo-electron microscopy to visualize the molecular structure of such a protein complex, an enzyme called HMPV L:P polymerase.
Cryo-EM is an advanced electron-scanning microscopy, that images samples cooled to cryogenic temperatures down to the sub-nanometer range. The images of HMPV L:P polymerase captured had a resolution of 0.37 nanometers. The team used these two-dimensional images to built three-dimensional models of the enzyme structure.
Key sites for molecular interactions were revealed after the analysis of the models. These sites could be potential targets for designing new antiviral molecules. This detailed structural knowledge of key pneumonia virus enzyme would give new insights to the researchers to develop molecules that inhibit the enzymatic activities of HPMV L:P protein, thus preventing viral infections.
“We hope that our work will help researchers in pharma and academia around the world to design much-needed therapies for difficult viral infections that often lead to antibiotic-resistant bacterial infections,” said Dr. Lescar.
The HMPV viruses were evolutionarily stable and showed a close association with RSV and other viruses in the Pneumorivridae family. For this reason, the NUT scientists hope that the antivirals developed against HMPV could essentially target a broad spectrum of viruses causing respiratory diseases and might help in the research against other viral infections.
Dr. Lescar and colleagues have started a company named Epitoire that is actively involved in designing DNA replication inhibitors against these viruses as potential drugs, and Epitoire is currently looking for investors and clinicians to support it.
Editor’s Note; NTU scientists develop a 3D model of key pneumonia virus enzyme, uses Cryo-EM to image the enzyme.