Existing Anti-Hypertension Drug Could Help Fight Flu

Anti-hypertensive drugs called calcium channel blockers can suppress influenza virus replication by blocking a key viral receptor.

AsianScientist (Jun. 12, 2018) – In a study published in Cell Host & Microbe, scientists in Japan have identified a receptor involved in flu virus infection, providing a novel target for anti-flu drug development.

Viral infection starts when a virus particle attaches to a receptor molecule on the surface of a host cell. The virus particle then hijacks cellular machinery to enter the cell and replicate itself, establishing the infection. The key receptor molecule for the influenza A virus (IAV) has remained unidentified despite decades of research.

In the present study, scientists led by Professor Yusuke Ohba of Hokkaido University, Japan, have discovered that the Ca2+ channel—a transmembrane protein that allows Ca2+ to move across the cell membrane—is a key receptor molecule for IAV infections.

In experiments using cultured human cells, the team found that IAV binds to the Ca2+ channel on the cell’s surface to trigger an influx of Ca2+, followed by entry of the virus and infection. Knocking down Ca2+ channels inhibited IAV-induced Ca2+ influx and virus entry. The researchers also revealed that sialic acid on the Ca2+ channel is crucial for the virus to bind.

Finally, the team tested the effect of calcium channel blockers (CCB) on IAV infections in mice. CCBs are commonly used as anti-hypertension drugs. When the researchers treated the animals with CCB intranasally, a significant and dose-dependent reduction in virus replication was observed. When the animals were treated with high amounts of IAV, administration of CCB significantly prolonged survival and allowed weight recovery of the survivors, whereas the untreated group died within five days.

“There were cases when the suppressive effect of CCB on IAV infections was comparable to that of an existing anti-flu drug. We expect that the interaction between IAV and the Ca2+ channel could be a novel and important target for future drug development,” said Ohba.

The article can be found at: Fujioka et al. (2018) A Sialylated Voltage-Dependent Ca2+ Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into Mammalian Cells.


Source: Hokkaido University; Photo: Shutterstock.
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