University of Connecticut (UConn) researchers have identified a compound that can successfully block the Porcine Reproductive and Respiratory Syndrome (PRRS) virus.
PRRS is a highly contagious disease that affects both young and adult pigs. It’s the most economically damaging virus in the pork industry throughout the world. In the U.S. alone, the virus is responsible for approximately $600 million in annual losses for farmers.
UConn assistant professor of animal science, Young Tang, and Antonio Garmendia, professor of pathobiology and veterinary science, have successfully identified compounds that can effectively block the virus from infecting pig cells, creating a promising pathway to an alternative treatment, UConn reports in a release. The researchers published their findings in Virology Journal.
The UConn research team identified CD163, a cell surface receptor that is expressed in pig monocytes and macrophages that the virus needs to get into the pig target cells. They hypothesized that a small molecule blocking this receptor would block infection, the release said.
In collaboration with Atomwise, a biotechnology company in San Francisco, the researchers used artificial intelligence technology to screen millions of compounds and identify small molecules that could block CD163. After identifying the best candidates, the company sent Tang and Garmendia 74 small molecules – predicted to have the highest potential of targeting the receptor – to test in their labs, the release said.
Using a bimolecular fluorescence complementation (BiFC) assay, the researchers were able 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 they did not observe fluorescence, this meant the small molecule successfully blocked the virus.
One of the compounds, B7, blocked the formation of fluorescence in the BiFC assay. In follow-up assays, B7 blocked the virus infection of pig cells, becoming the very first in vitro study demonstrating successful inhibition of viral receptor recognition by the PRRS virus, the release said.
“There are many strains of the PRRS virus, making attempts to create broadly protective vaccines very challenging,” the article said. “Vaccines work by spurring the body to produce antibodies specific for the strain of virus used as the vaccine. Because the virus mutates so quickly and has so many strains, it is impossible to vaccinate pigs against every variant.”
The researchers then tested the small molecules from Atomwise with both the American and European types of the virus and found that B7 effectively blocks both types. In addition, these types are genetically diverse, making this finding’s broad applicability significant.
Coupled with existing vaccines, this compound would provide a second line of defense against PRRS, the researchers said in the article. Vaccines prompt the creation of antibodies, and the small molecule would block the virus’ attachment to cell receptors, reducing further virus shedding and transmission.
“This would protect animals better than a vaccine alone,” Garmendia said in the release. “It could have a significant impact.”
They also identified several B7 analogs that produced similar results, the release noted.
With support from UConn Technology Commercialization Services, the team has filed a provisional patent for this advancement and are seeking industry partners. The next step for this research is to perform in vivo experiments (in animals).
“If we find it can be as effective in vivo as it is in vitro with low toxicity to the pigs, we can say we’ve found a cure for this disease,” Tang said in the release.
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