Virus Mutates To Combat New Drug Still in Lab

Scientists from the European Molecular Biology Laboratory (EMBL) have investigated how the influenza virus responds to the new drug treatment Xofluza, developed in Japan.

The new drug for the influenza virus has now been investigated, with scientists looking at the drug’s mode of action in detail before uncovering possible mechanisms by which viral resistance to it could emerge.

Around 290,000 to 650,000 deaths and 3-5 million cases of severe illness worldwide every year are associated with influenza virus. Vaccines and anti-viral drugs are available for flu, however, viral strains with resistance to these are emerging.

The need for an effective drug is therefore high.

The first influenza drug

According to EMBL, Xofluza (baloxavir marboxil) is the first entirely new anti-influenza drug approved for clinical use since the 1990s. The body metabolizes Xofluza into baloxavir acid, which inhibits a key viral enzyme known as influenza polymerase.

With this enzyme inactivated, the virus is unable to replicate, and an infection cannot proceed. Clinical trials on healthy patients have shown that one oral dose of Xofluza is effective in reducing viral production and relieving symptoms.

The researchers investigated the model of action of the drug and possible mechanisms of which viral resistance to it could emerge.

During two trails, scientist took swabs which showed that in a minority of treated patients, a specific mutation occurs in the virus’s polymerase enzyme.

Shinya Omoto, co-corresponding author of the paper said: “This mutation makes the virus around 30-50 times less susceptible to the drug. However, this mutation also caused impairment of viral replication, and did not seem to have a negative effect on the treatment outcome so far.”

What effects does the new drug have on influenza virus?

The group at EMBL determined crystal structures of the drug bound to the typical polymerase of the virus as well as the mutant polymerase.

The mutation leads to a very small structural change; that is, one amino acid is mutated into another, smaller one by just a single methyl group. Stephen Cusack, leader of the research group said: “Still, this apparently minor change leads to reduced contact between the polymerase and the drug, weakening the drug’s effect. However, the virus pays a price for escaping the drug, since we found that the same mutation also lowers the activity of the polymerase, meaning that the mutant virus is less effective at replicating itself. It is therefore uncertain whether this Xofluza-resistant virus would ever spread.”

The information from this study will allow the researchers to modify the drug and improve it further.

Source:   https://www.scitecheuropa.eu/influenza-virus-respond-new-drug/87617/