Designing anti-Zika virus peptides derived from predicted human-Zika virus protein-protein interactions
Citation
Kazmirchuk, T., Dick, K., Burnside, D.J., Barnes, B., Moteshareie, H., Hajikarimlou, M., Omidi, K., Ahmed, D., Low, A., Lettl, C., Hooshyar, M., Schoenrock, A., Pitre, S., Babu, M., Cassol, E., Samanfar, B., Wong, A., Dehne, F., Green, J.R., Golshani, A. (2017). Designing anti-Zika virus peptides derived from predicted human-Zika virus protein-protein interactions. Computational Biology and Chemistry, [online] 71 180-187. http://dx.doi.org/10.1016/j.compbiolchem.2017.10.011
Plain language summary
The Zika virus (ZIKV) is currently causing an ongoing pandemic, incurring considerable human impact. The rapid spread of the virus throughout the Western hemisphere has driven a significant accumulation of knowledge on ZIKV infection.
Host-virus protein–protein interactions (PPIs) are essential for viral infection and propagation as well as neuroinvasion. Investigating the host-virus interactome is an important step in
identifying targets for novel anti-viral therapeutics.
Considering that the World Health Organization has lifted the declaration of emergency
for the ZIKV, shifting to threat management of the ZIKV is important as many mechanisms of pathogenesis are still unclear. The designed peptides provided here may therefore prove to be
useful therapeutics against ZIKV infection, and could aid in overall
ZIKV management.
Abstract
The production of anti-Zika virus (ZIKV) therapeutics has become increasingly important as the propagation of the devastating virus continues largely unchecked. Notably, a causal relationship between ZIKV infection and neurodevelopmental abnormalities has been widely reported, yet a specific mechanism underlying impaired neurological development has not been identified. Here, we report on the design of several synthetic competitive inhibitory peptides against key pathogenic ZIKV proteins through the prediction of protein–protein interactions (PPIs). Often, PPIs between host and viral proteins are crucial for infection and pathogenesis, making them attractive targets for therapeutics. Using two complementary sequence-based PPI prediction tools, we first produced a comprehensive map of predicted human-ZIKV PPIs (involving 209 human protein candidates). We then designed several peptides intended to disrupt the corresponding host-pathogen interactions thereby acting as anti-ZIKV therapeutics. The data generated in this study constitute a foundational resource to aid in the multi-disciplinary effort to combat ZIKV infection, including the design of additional synthetic proteins.