WASHINGTON, June 20 (Xinhua) -- American researchers identified how a naturally occurring enzyme in humans and other mammals had antiviral effects on a wide variety of viruses, including West Nile, hepatitis C, rabies, and HIV.
A study published on Wednesday in the journal Nature revealed that the compound called viperin could facilitate a reaction that produced a molecule that could prevent viruses from copying their genetic material and thus from multiplying.
"Viperin catalyzes an important reaction that results in the creation of a molecule called ddhCTP," said Craig Cameron, professor of biochemistry and molecular biology at the Pennsylvania State University and an author of the study.
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, according to Cameron.
"The molecule acts in a similar manner to drugs that were developed to treat viruses like HIV and hepatitis C," said Cameron.
NONTOXIC COMPOUND
A virus typically makes use of the host's genetic building blocks to copy its own genetic material, incorporating molecules called nucleotides into new strands of RNA.
The molecule called ddhCTP is found capable of mimicking these nucleotide building blocks and becoming incorporated into the virus' genome.
Once incorporated into a new strand of the virus' 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.
But such a paradigm is of no use when the virus infects an essential cell type with limited capacity for replenishment, according to the researchers.
"The major obstacle to developing therapeutically useful antiviral nucleotides is unintended targets," said Jamie Arnold, associate research professor of biochemistry and molecular biology at Penn State and an author of the paper.
"For example, a few years ago we discovered that a nucleotide analog under development for treatment of hepatitis C could interfere with the production of RNA in mitochondria, subcellular organelles important for energy production in the patient's own cells," said Arnold.
The molecule ddhCTP, however, does not appear to have any unintended targets, according to the study. The research team suggested that the natural origin of the compound within the human body necessitated that it be nontoxic.
"Unlike many of our current drugs, ddhCTP is encoded by the cells of humans and other mammals," said Cameron. "We have been synthesizing nucleotide analogs for years, but here we see that nature beat us to the punch and created a nucleotide analog that can deal with a virus in living cells and does not exhibit any toxicity to date."
BROAD SPECTRUM
To verify the effectiveness of ddhCTP, the research team showed that the molecule inhibited the RNA polymerases of dengue virus, West Nile virus and Zika virus, which are all in a group of viruses called flaviviruses. Then they investigated whether the molecule halted replication of Zika virus in living cells.
"The molecule directly inhibited replication of three different strains of Zika virus," said Joyce Jose, assistant professor of biochemistry and molecular biology at Penn State and an author of the paper.
"This is particularly exciting because there are no known treatments for Zika. This study highlights a new avenue of research into natural compounds like ddhCTP that could be used in future treatments," said Jose.
Together, these results demonstrated promising antiviral effects of ddhCTP on a variety of flaviviruses.
However, the RNA polymerases of human rhinovirus and poliovirus, which are in a group called picornaviruses, were not sensitive to the molecule.
The researchers planned to investigate the polymerase structures of these viruses to better understand why flaviviruses were sensitive to ddhCTP while the picornaviruses tested in this study were not. This investigation may also offer insights into how flaviviruses might develop resistance to the molecule.
"Development of resistance to an antiviral agent is always an issue," said Cameron. "Having some idea of how resistance happens, or being able to prevent it from happening, will be critical if this is to be used as a broad-spectrum therapy."
