Baloxavir Shows Broad Antiviral Activity Against Influenza A, B, C, and D

Antiviral drugs play an important role in fighting seasonal influenza A and B viruses, and now a new study by investigators with the US Centers for Disease Control and Prevention (CDC) has found that the drug baloxavir marboxil exhibits broad antiviral activity against influenza A and B, as well as against the less-common influenza C and D viruses.

Influenza viruses prone to mutation have exhibited resistance to current antiviral medications, which can help stop flu illness. Baloxavir was approved for use in Japan and the United States for the treatment of illness caused by influenza A and B viruses in 2018. A study published in January 2019 indicated that influenza A viruses exhibited reduced susceptibility to the single-dose antiviral, prompting investigators to closely monitor the drug’s activity. In the new study published in Emerging Infectious Diseases, CDC investigators say they’ve found baloxavir to work against diverse influenza viruses, suggesting that it could offer the first therapeutic option against influenza C virus infections.

“Influenza C viruses are known to infect humans, pigs, camels, and dogs. Unlike influenza A and B viruses, influenza C viruses typically cause mild illness. However, in recent years, severe illness in children infected by influenza C virus has raised concerns over the lack of virus-specific therapeutics and vaccines,” the investigators explained. “Antiviral drugs have been used to mitigate zoonotic virus outbreaks and are central to pandemic preparedness. However, therapeutic options remain limited and drug-resistant viruses can emerge after treatment, spontaneous mutation, or reassortment.”

Influenza D viruses, which were initially isolated in a pig in 2011, have since been found in bovines. Although there have been no reported human infections, antibodies for influenza D have been detected in people exposed to cattle. In the new study, investigators aimed to determine the effectiveness of baloxavir against the 4 types of influenza viruses. Because the active site of the polymerase acidic protein is nearly identical in influenza A, B, C, and D viruses, the study team hypothesized that baloxavir would inhibit replication of all 4 influenza virus types. Using a virus yield reduction assay, the investigators first tested 2 viruses of each type against baloxavir and included the broad-spectrum antiviral drug favipiravir as a control.

“On the basis of 90% effective concentration values determined at 48 hours post-infection, influenza A viruses were most susceptible to baloxavir and influenza D viruses least susceptible,” the research team found, noting that baloxavir susceptibility for influenza B viruses was about 3 times lower. For influenza C viruses, susceptibility was about 6 times lower than it was for influenza A viruses. “Favipiravir also showed inhibitory effects against all virus types, although much higher concentrations were required to achieve similar levels of reduction.”

In addition, the study team used focus-reduction assay and a high-content imaging neutralization test to test 25 influenza viruses of avian origin of the H5, H6, H7, H9 and H10 subtypes. They found that this range of viruses were susceptible to baloxavir, as were 30 swine-origin viruses collected over many years from different lineages and subtypes.

“Baloxavir displayed broad antiviral activity against diverse influenza viruses, including all 4 types and animal-origin influenza A viruses with pandemic potential,” the investigators concluded, noting that additional studies on a large collection of influenza C viruses is needed to further asses susceptibility to baloxavir. “Ongoing monitoring of baloxavir susceptibility of emerging avian and swine influenza A viruses with pandemic potential is needed to inform clinical management and public health preparedness efforts.”