The research, published recently in the journal Cell Host and Microbe, paves the way for developing new therapeutics for these infections with no or very limited treatments.
“Our findings bring us one step closer to understanding and treating currently untreatable mosquito-transmitted pathogens, which are an ever-increasing threat to global human populations,” said Michaela Gack, Scientific Director of Cleveland Clinic’s Florida Research & Innovation Center.
“Our commitment to studying viral pathogens and host enzymes in novel ways may ultimately help us develop new, effective treatments to prevent future threats to human health,” Gack said in a statement.
Viruses cannot survive on their own. While they contain their own genetic material, they don’t carry all the genes or factors they need to live and reproduce. That is why viruses infect hosts — they hijack mammalian cells to turn them into virus-making factories.
To take control of the infected host cell, the Zika virus, for example, hijacks several proteins inside the cell for its efficient replication.
Humans have many enzymes that “tag” proteins with other molecules allowing them to function properly.
Since the Zika virus is missing certain molecules necessary for its reproduction, it has evolved to utilise a human enzyme called KAT5? (an acetyltransferase) which helps the virus to amplify its RNA genome in viral replication complexes.
The discovery of KAT5?’s critical role in virus replication is the key first step in beginning to design inhibitory molecules to stop viral replication and treat infection.
“Viruses mutate so much that drugging them directly might lose effectivity over time—this is what is known as antiviral drug resistance. Human proteins don’t change rapidly,” explains the study’s second author Cindy Chiang from Cleveland Clinic, US.
“Targeting the host’s KAT5? protein should be much more effective in the long term to treat these viruses,” Chiang said.
The study suggests that creating drugs targeting the human KAT5? enzyme might help target not only Zika but also several other mosquito-transmitted flaviviruses.