Small molecules block PRRSV from infecting pig cells
Researchers at the University of Connecticut have identified compounds that can block porcine reproductive and respiratory syndrome virus (PRRSV) from infecting pig cells, creating a promising pathway to an alternative treatment. Their findings are published in Virology Journal.
CD163, expressed in pig monocytes and macrophages, is a key receptor for PRRSV infection. The University of Connecticut team, including assistant professor of animal science Young Tang and Antonio Garmendia, professor of pathobiology and veterinary science, hypothesized that a small molecule blocking CD163 would block infection.
In collaboration with Atomwise, a biotechnology company in San Francisco, Tang and Garmendia used artificial intelligence (AI) technology to virtually screen millions of compounds and identify small molecules that could block CD163. After identifying the best candidates, Atomwise sent Tang and Garmendia 74 small molecules predicted to have the highest potential of targeting the receptor to test in their labs.
The University of Connecticut researchers then used a bimolecular fluorescence complementation (BiFC) assay to determine if the compounds could block the viral glycoproteins from interaction with the cell receptor. When proteins interact, they generate fluorescence in the assay, which, in this case, indicates the viral glycoprotein binds to the receptor. When the researchers did not observe fluorescence, this meant the small molecule successfully blocked the virus.
They found that one of the predicted compounds, named B7, blocked the formation of fluorescence in the BiFC assay. In follow-up assays, they determined that B7 blocked the virus infection of pig cells, becoming the first in vitro study demonstrating successful inhibition of viral receptor recognition by the PRRS virus.
There are many strains of PRRSV, making attempts to create broadly protective vaccines challenging. The researchers tested the small molecules from Atomwise with both the American and European types of the virus and found that B7 effectively blocks both. These two types are genetically diverse, making this finding’s broad applicability significant.
Coupled with existing vaccines, this compound would provide a second line of defence against PRRS. While vaccines prompt the creation of antibodies, the small molecule would block the virus’ attachment to cell receptors, reducing further virus shedding and transmission.
The research collaboration also identified several B7 analogues that produced similar results. By identifying these analogues with similar structures, the researchers gleaned a better idea of which of several chemical groups on B7 were responsible for disrupting the viral infection.
The researchers have filed a provisional patent for this advancement and are actively seeking industry partners. The next step for this research is to perform in vivo experiments to further test the effectiveness of these small molecules in infected pigs.
Article: Huang, C., Bernard, D., Zhu, J., Dash, R. C., Chu, A., Knupp, A., Hakey, A., Hadden, M. K., Garmendia, A., Tang, Y. (2020). Small molecules block the interaction between porcine reproductive and respiratory syndrome virus and CD163 receptor and the infection of pig cells. Virology Journal, 17(1), 116, doi: 10.1186/s12985-020-01361-7
[SOURCE: University of Connecticut]