|By: The OpenZika research team|
|23 Jul 2020|
As the OpenZika research team wrapped up their work on World Community Grid, they identified a promising compound in the ongoing search for Zika treatments.
Members of the OpenZika Brazil team (left to right): Melina Mottin, Carolina Andrade, Bruna Souza, and Paulo Ramos.
Members of the OpenZika US team at Collaborations Pharmeceuticals (left to right): Sean Ekins, Daniel Foil, Kimberley Zorn, Ana Puhl Rubio, Jennifer Klein, Maggie Hupcey, Thomas Lane, Andrea Barry (business advisor)
The OpenZika project was created to identify potential treatments for people who were infected by the Zika virus. Specifically, the project targeted key proteins that the virus uses to survive and spread in the body, based on what is known from similar diseases, such as dengue and yellow fever. In order to develop treatments, the researchers aimed to identify which of millions of chemical compounds could be effective at interfering with these key proteins.
The researchers looked at which chemical compounds might be effective against the apo NS3 helicase crystal structure (apo means that the protein was not bound to anything else, such as a cofactor, inhibitor, or nucleic acid). The NS3 helicase is important because it is a component of the Zika virus (ZIKV) that allows it to replicate. You can learn more about helicases here.
A Potential Treatment
In late 2019, the OpenZika researchers published a paper in Scientific Reports which outlined their work showing that a synthetic compound called FAM E3 can inhibit ZIKV infection by blocking the genome replication stage. Through molecular docking work on World Community Grid, the researchers were able to predict a possible interaction between FAM E3 and the ZIKV NS3 helicase. Based on the molecular docking results, the researchers investigated the interaction in vitro and demonstrated that FAM E3 could bind to and stabilize NS3.
You can read the paper here. The results may be useful for further development of Zika antivirals, as well as for a better understanding of how exactly this synthetic compound inhibits viral replication.
Like many scientists with extensive experience with infectious disease research, the OpenZika team is currently doing work related to SARS-CoV-2. In May, the team published a perspective in Drug Discovery Today regarding drug discovery projects for SARS-CoV-2. This paper mentions what they learned through their experiences with previous projects, including the OpenZika project.
The research team has also begun writing a new paper on the results from the project's virtual screening of NS3 helicase and NS2B-NS3 protease, with the results in vitro in ZIKV and also in the proteins.
Thank you to the many volunteers around the world who supported this project during its time on World Community Grid.