Building upon previous research that revealed a method of manipulating a key viral replication enzyme, an international group of virologists have discovered a new class of compounds that are capable of killing the influenza virus.
It is hoped that the new compounds will lead to the development of anti-influenza drugs that the virus strains can’t adapt to and/or resist as easily as they do Tamiful — an anti-influenza drug that is becoming less and less effective due to the virus’ ability to rapidly mutate and thus adapt to the drugs.
Tamiful and another anti-influenza drug, Relenza, work by disrupting the activity of the viral enzyme neuraminidase (the ‘N’ in viral designations, such as H1N1); the enzyme helps the virus to detach from an infected cell’s surface by digesting a cell surface sugar called sialic acid. This same sugar is used by the virus to help it stick to a cell’s surface prior to it invading the new cell where it can begin replicating.
Acting on the premise that ‘too much of a good thing can be deadly’ (for the virus that is), the scientists decided to exploit this viral mechanism by “gumming” it up, so to speak.
The newly discovered compounds are able to block, or “clog up” this normal neuraminidase activity — stopping the enzyme from dissolving the surface sugar which in turn prevents the virus from detaching itself and escaping to infect another health cell.These new sialic acid analogues — termed neuraminidase inhibitors — are also more effective because they are water soluble; after being taken orally, they more easily localize to a patient’s throat where the flu virus is replicating.
In a press release, Masahiro Niikura, research team member and associate professor of Health Science at Simon Fraser University, stated:
“Influenza develops resistance to Replenza less frequently, but it’s not the drug of choice like Tamiful because it’s not water-soluble and has to be taken as a nasal spray. Our new compounds are structurally more similar to sialic acid than Tamiful. We expect this closer match will make it much more difficult for influenza to adapt to new drugs.”
And, quoting from the paper’s abstract:
“These compounds function in cell-based assays and in animal models, with efficacies comparable to that of the neuraminidase inhibitor zanamivir and with broad spectrum activity against drug-resistant strains in vitro. The similarity of their structure to that of the natural substrate and their mechanism-based design make these attractive antiviral candidates.”
The study, detailing the newly discovered compounds and how they work, was published on-line, Feb. 21, in the journal Science Express under the title: ‘Mechanism-Based Covalent Neuraminidase Inhibitors with Broad Spectrum Influenza Antiviral Activity’
Top photo: ‘Simon Fraser University virologist Masahiro Niikura and his doctoral student Nicole Bance have helped find a new enemy capable of killing the potentially deadly and always changing influenza virus’ – credit: SFU Public Affairs and Media Relations