Baloxavir shows promise against H5N1 bird flu as other antivirals fall short

The transcontinental spread of highly pathogenic avian influenza A(H5N1) viruses poses a significant public health threat due to their ability to cross the interspecies barrier. An increase in the number of human infections, high mortality rates and low pre-existing population immunity are matters of significant public health concern. When vaccines are not readily available, antivirals play a pivotal role in preventing and controlling influenza outbreaks. It is critical to understand whether clinically approved anti-influenza therapeutics are effective against emerging zoonotic pathogens. A study led by Elena Govorkova, MD, PhD, in the lab of Richard Webby, PhD, Department of Host-Microbe Interactions, evaluated four influenza antivirals with different mechanisms of action. The researchers compared how well the antivirals protected against lethal A(H5N1) infections in a preclinical model. 

The results indicate that most existing antivirals — including the neuraminidase inhibitor, oseltamivir, which is a standard of care for acute uncomplicated influenza — were largely ineffective at doses equivalent to those used in humans. The active metabolite of baloxavir was the only medication that reduced viral replication in the lungs, prevented neuroinvasion and improved survival of animals. These findings, suggesting baloxavir may be the most reliable A(H5N1) influenza countermeasure to be considered in public health preparedness and response efforts, were published in Nature Communications.

“Preclinical studies provide essential information for establishing proper regimens for existing antiviral drugs and guide the development of novel therapies,” explained Govorkova. “These studies can help reduce influenza viral loads, limit transmission and manage severe infections, ultimately reducing morbidity and mortality until effective, antigenically matched vaccines are available.”

“We still have strategies available to control A(H5N1) infections and mitigate outbreak risks, but our antiviral armamentarium may actually be smaller than expected,” said first author Konstantin Andreev, PhD, Department of Host Microbe Interactions. “We need further insight into the mechanisms behind these reduced responses and develop more effective interventions.”

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