Compound made inside human body stops viruses from replicating

[Judi Lynn]

Date:
June 20, 2018
Source:
Penn State

The newest antiviral drugs could take advantage of a compound made not by humans, but inside them. A team of researchers has identified the mode of action of viperin, a naturally occurring enzyme in humans and other mammals that is known to have antiviral effects on a wide variety of viruses, including West Nile, hepatitis C, rabies, and HIV.

The enzyme facilitates a reaction that produces the molecule ddhCTP, which prevents viruses from copying their genetic material and thus from multiplying. This discovery could allow researchers to develop a drug that induces the human body to produce this molecule and could act as a broad-spectrum therapy for a range of viruses. A paper describing the study appears online on June 20th in the journal Nature.

"We knew viperin had broad antiviral effects through some sort of enzymatic activity, but other antivirals use a different method to stop viruses," said Craig Cameron, professor and holder of the Eberly Chair in Biochemistry and Molecular Biology at Penn State and an author of the study. "Our collaborators at the Albert Einstein College of Medicine, led by senior authors Tyler Grove and Steven Almo, revealed that viperin catalyzes an important reaction that results in the creation of a molecule called ddhCTP. Our team at Penn State then showed the effects of ddhCTP on a virus's ability to replicate its genetic material. Surprisingly, the molecule acts in a similar manner to drugs that were developed to treat viruses like HIV and hepatitis C. With a better understanding of how viperin prevents viruses from replicating, we hope to be able to design better antivirals."

A virus typically co-opts the host's genetic building blocks to copy its own genetic material, incorporating molecules called nucleotides into new strands of RNA. The molecule ddhCTP mimics these nucleotide building blocks and becomes incorporated into the virus's genome. Once incorporated into a new strand of the virus's RNA, these "nucleotide analogs" prevent an enzyme called RNA polymerase from adding more nucleotides to the strand, thus preventing the virus from making new copies of its genetic material.

More:
https://www.sciencedaily.com/releases/2018/06/180620150150.htm