Novel drug target may lead to a universal antiviral vaccine

A potential new drug target that could lead to a vaccine against a host of viral infectious diseases has been identified, scientists said on Wednesday.

The novel coronavirus outbreak in China shows viruses are a constant threat to humanity, the researchers from the Massachusetts General Hospital (MGH) in the US noted. The research, published in the journal Cell Reports, suggests that the protein Argonaute 4 (AGO4) is an "Achilles heel" for viruses. AGO4 is one of a family of AGO proteins.

Until now, there has been little evidence of why they are important, the researchers said. They found that AGO4 plays a key role in protecting cells against viral infections. Specifically, this protein is uniquely antiviral in mammalian immune cells, the researchers said. The group studied the anti-viral effects of several Argonaute proteins, and found that low levels of AGO4 make mammalian cells more likely to become infected. The researchers suggest that boosting levels of AGO4 could shore up the immune system to protect against multiple viruses.

"The goal is to understand how our immune system works so we can create treatments that work against a range of viruses, rather than just vaccines against a particular one," said Kate L Jeffrey, who led the study. Mammals have four Argonaute proteins (1-4), which act by silencing genes and which are remarkably conserved throughout multiple living things, including plants. The researchers said these are RNAi and microRNA effector proteins, and RNAi is the major antiviral defence strategy in plants and invertebrates.

Studies of influenza infected mice have shown that AGO4-deficient animals have significantly higher levels of the virus. The next steps are to "determine how broad spectrum this is to any virus type," said Jeffrey. "Then we need to discover how to boost AGO4 to ramp up protection against viral infections," she said.