Version 1
: Received: 16 October 2024 / Approved: 16 October 2024 / Online: 16 October 2024 (11:52:39 CEST)
How to cite:
Atchison, E. B.; Croft, S. N.; Mathew, C.; Brookes, D. W.; Coates, M.; Ito, K.; Ghildyal, R. An Interaction Between the Matrix Protein and the Polymerase Complex of Respiratory Syncytial Virus. Preprints2024, 2024101267. https://doi.org/10.20944/preprints202410.1267.v1
Atchison, E. B.; Croft, S. N.; Mathew, C.; Brookes, D. W.; Coates, M.; Ito, K.; Ghildyal, R. An Interaction Between the Matrix Protein and the Polymerase Complex of Respiratory Syncytial Virus. Preprints 2024, 2024101267. https://doi.org/10.20944/preprints202410.1267.v1
Atchison, E. B.; Croft, S. N.; Mathew, C.; Brookes, D. W.; Coates, M.; Ito, K.; Ghildyal, R. An Interaction Between the Matrix Protein and the Polymerase Complex of Respiratory Syncytial Virus. Preprints2024, 2024101267. https://doi.org/10.20944/preprints202410.1267.v1
APA Style
Atchison, E. B., Croft, S. N., Mathew, C., Brookes, D. W., Coates, M., Ito, K., & Ghildyal, R. (2024). An Interaction Between the Matrix Protein and the Polymerase Complex of Respiratory Syncytial Virus. Preprints. https://doi.org/10.20944/preprints202410.1267.v1
Chicago/Turabian Style
Atchison, E. B., Kazuhiro Ito and Reena Ghildyal. 2024 "An Interaction Between the Matrix Protein and the Polymerase Complex of Respiratory Syncytial Virus" Preprints. https://doi.org/10.20944/preprints202410.1267.v1
Abstract
The global burden of respiratory syncytial virus (RSV) and severe associated disease is prodigious. RSV specific vaccines have been launched recently but there is no antiviral medicine commercially available. RSV polymerase (L) protein is one of the promising antiviral targets along with fusion and nucleocapsid proteins. During medicinal chemis-try campaign, two potent L-protein inhibitors (PC786 and PC751) were identified. Both compounds inhibited RSV A/B-induced cytopathic effect in HEp-2 cells equally, but PC786 was more potent than PC751 in bronchial epithelial cells. Repeated treatment with escalating concentrations on RSV A2 infected HEp-2 cells revealed both inhibitors led to a Y1631H mutation in the L protein, but only PC786 induced a mutation in the M protein (V153A). By L-protein fragment and M protein binding analysis, we showed that the M protein interacts with the 1392-1735 amino acid region of the L protein, where potentially PC786 binds. In addition, PC786 treatment or PC786 induced mutant RSV was found to increase M protein nuclear localisation later in infection concomitant with delayed fusion protein localisation at the budding viral filaments. As M protein is known to play a key role in virus assembly and budding late in infection, our data suggests that disrupting the interaction between M and L could provide a novel target for antiviral development.
Keywords
Respiratory Syncytial virus; L protein; M protein; air liquid interface culture; bronchial epithelium; nuclear translocation
Subject
Biology and Life Sciences, Virology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
