Concanamycin A can stop the multiplication of influenza viruses

Concanamycin A is an antibiotic derived from S. diastatochromogenes. It is shown to be effective against some fungi and yeasts. Concanamycin A is considered a highly potent inhibitor of ATP-driven proton pumps, which are also called vacuolar-type H+ATPases (V-ATPases). These lower the ph of intracellular compartments and transport protons across the plasma membrane. They are enormously important in endocytosis and intracellular membrane transport.

Concanamycin A in combination with influenza viruses

Concanamycin A was shown to block the entry of influenza viral cells when present in the initial phase of infection. It is not the case that the attachment of the virus particles to the cells is prevented. Rather, the exit of the influenza virus from the endosome is the crucial step that is prevented by the antibiotic. Accordingly, the virus remains trapped in the endosome and is unable to replicate.

This process, which inhibits the entry of influenza virus into cells, occurs under acidic conditions. When the pH gradient is abolished by pre-incubation of cells at acidic pH, influenza virus entry does not occur even in the absence of inhibitors. This suggests that acidic conditions alone are not sufficient to promote viral entry into cells. For this step, viral infection needs a pH gradient.

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Reference:
Guinea R, Carrasco L. Concanamycin A blocks influenza virus entry into cells under acidic conditions. FEBS Lett. 1994 Aug 8;349(3):327-30. doi: 10.1016/0014-5793(94)00695-4. PMID: 8050591.

 

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