Structure of Zika protein elucidated

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Researchers from the University of California, Riverside (CA, USA), have reported the full structure of nonstructural protein 5 (NS5) in Zika virus (ZIKV), which is critical for viral replication and could present a target for future drug development.

It is known that genomic replication of ZIKV is reliant on NS5 through RNA capping and RNA polymerase activities present in the protein. This study, published recently in Nature Communications, reported the crystal structure of the entire NS5 protein, also demonstrating the protein is functional when purified in vitro.

Co-leader of the study, Jikui Song (University of California, Riverside) commented: “We started this work realizing that the full structure of ZIKV NS5 was missing. The main challenge for us occurred during the protein’s purification process when ZIKV NS5 got degraded – chopped up – by bacterial enzymes.”

To overcome this barrier the team developed a new and efficient protocol for purifying the protein and succeeded in determining the crystal structure of NS5. In addition, the researchers carried out structural analyses, revealing a potential inhibitor binding site on the protein. This finding provides a strong basis for developing potential antivirals targeting NS5 and therefore suppressing ZIKV replication.

The team hope to build on their research by investigating the antiviral potential of a known chemical compound on NS5; the drug has previously been demonstrated to work effectively in related-virus dengue.

Rong Hai, co-leader of the study from the University of California, Riverside, explained: “Our work provides a framework for future studies of ZIKV NS5 and opportunities for drug development against ZIKV based on its structural similarity to the NS5 protein of other flaviviruses, such as the dengue virus. No doubt, ZIKV therapeutics can benefit from the wealth of knowledge that has already been generated in the dengue virus field.”

Sources: Zhao B, Yi G, Du F et al. Structure and function of the Zika virus full-length NS5 protein, Nat. Comms. doi:10.1038/ncomms14762 (2017) (Epub ahead of print); https://ucrtoday.ucr.edu/45678

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