Human cytomegalovirus inhibitor AL18 also possesses activity against influenza A and B viruses
Giulia Muratore1, Beatrice Mercorelli, Laura Goracci
1Department of Molecular Medicine, University of Padua, Padua, Italy.
Abstract:
AL18, an inhibitor of human cytomegalovirus DNA polymerase, was serendipitously found to also block the interaction between the PB1 and PA polymerase subunits of influenza A virus. Furthermore, AL18 effectively inhibited influenza A virus polymerase activity and the overall replication of influenza A and B viruses. A molecular model to explain the binding of AL18 to both cytomegalovirus and influenza targets is proposed. Thus, AL18 represents an interesting lead for the development of new antivirals.
Insights
A novel antiviral compound, AL18, initially targeting cytomegalovirus, unexpectedly inhibits influenza A and B virus replication by blocking essential polymerase subunit interactions. This discovery offers a promising new avenue for developing broad-spectrum antiviral therapies.
Area of Science:
- Virology
- Drug Discovery
- Molecular Biology
Background:
- Human cytomegalovirus (CMV) and influenza viruses are significant human pathogens.
- Antiviral drug development often involves repurposing existing compounds or identifying novel mechanisms of action.
Purpose of the Study:
- To investigate the unexpected antiviral activity of AL18, a CMV DNA polymerase inhibitor, against influenza viruses.
- To elucidate the molecular mechanism by which AL18 affects influenza virus replication.
Main Methods:
- Biochemical assays to assess polymerase activity.
- Viral replication assays in cell culture.
- Molecular modeling to predict drug-target interactions.
Main Results:
- AL18 was found to inhibit the interaction between PB1 and PA polymerase subunits of influenza A virus.
- AL18 demonstrated potent inhibition of influenza A virus polymerase activity.
- AL18 effectively suppressed the replication of both influenza A and B viruses.
Conclusions:
- AL18 exhibits dual activity, inhibiting both CMV and influenza virus replication.
- The compound acts by disrupting the influenza virus polymerase complex.
- AL18 represents a promising lead compound for developing new antiviral agents against influenza and potentially other viruses.
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