A new compound that inhibits the replication of hepatitis C virus (HCV) in several stages of its lifecycle — and is also capable of acting on bacteria, fungi and cancer cells — has been synthesized by researchers at São Paulo State University (UNESP) in Brazil.
“We discovered that the compound acts on HCV in almost all stages of its reproductive cycle, which is unusual for antivirals. They generally have specific isolated targets, such as capsid proteins, membrane receptors or specific proteins such as NS3, inhibiting specific processes such as viral cell entry, the synthesis of genetic material and proteins, or the assembly and release of new viral particles. GA-Hecate, in contrast, showed broad activity encompassing several stages of the cycle,” Sanches explained.
“The compound also displayed activity in lipid droplets, small lipid organelles in cells that are used by HCV during its replication and assembly and that protect the virus from attack by enzymes. GA-Hecate breaks these lipid droplets down and leaves the virus’s replicative complex exposed to the action of cellular enzymes.”
The researchers tested GA-Hecate both on the complete virus and on its “subgenome replicons,” which contain all the elements required by the virus for replication of its genetic material in cells but are incapable of synthesizing the proteins responsible for infection. The compound was effective in all tests. Another positive property of the compound is that it is highly selective, meaning it attacks the virus rather than the host cells. As such, it has the potential to be used as a drug for the treatment of the disease.
“Although the compound didn’t display significant action on erythrocytes — red blood cells — the molecule has to undergo changes in its structure to reduce its toxicity still further,” Sanches said. “This is what we’re working on now, so that our research can move on from the in vitro stage to the in vivo stage.” According to Professor Eduardo Maffud Cilli, who supervised Sanches’s PhD research at UNESP’s Chemistry Institute in Araraquara, “the average time it takes to plan and develop therapeutic peptides is ten years. A study with this estimate has just come out. So far, approximately two years have been spent on developing the GA-Hecate molecule. Considering the statistical average, another eight years will be needed until the drug can come to market.”
GA-Hecate antiviral properties on HCV whole cycle represent a new antiviral class and open the door for the development of broad spectrum antivirals. Scientific Reports, 2018; 8 (1) DOI: 10.1038/s41598-018-32176-w