Article ; Online: EPAC1 Pharmacological Inhibition with AM-001 Prevents SARS-CoV-2 and Influenza A Virus Replication in Cells.
2023 Volume 15, Issue 2
Abstract: The exceptional impact of the COVID-19 pandemic has stimulated an intense search for antiviral molecules. Host-targeted antiviral molecules have the potential of presenting broad-spectrum antiviral activity and are also considered as less likely to ... ...
| Abstract | The exceptional impact of the COVID-19 pandemic has stimulated an intense search for antiviral molecules. Host-targeted antiviral molecules have the potential of presenting broad-spectrum antiviral activity and are also considered as less likely to select for resistant viruses. In this study, we investigated the antiviral activity exerted by AM-001, a specific pharmacological inhibitor of EPAC1, a host exchange protein directly activated by cyclic AMP (cAMP). The cAMP-sensitive protein, EPAC1 regulates various physiological and pathological processes but its role in SARS-CoV-2 and influenza A virus infection has not yet been studied. Here, we provide evidence that the EPAC1 specific inhibitor AM-001 exerts potent antiviral activity against SARS-CoV-2 in the human lung Calu-3 cell line and the African green monkey Vero cell line. We observed a concentration-dependent inhibition of SARS-CoV-2 infectious viral particles and viral RNA release in the supernatants of AM-001 treated cells that was not associated with a significant impact on cellular viability. Furthermore, we identified AM-001 as an inhibitor of influenza A virus in Calu-3 cells. Altogether these results identify EPAC1 inhibition as a promising therapeutic target against viral infections. |
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| MeSH term(s) | Humans ; Antiviral Agents/pharmacology ; Chlorocebus aethiops ; COVID-19 ; Influenza A virus ; Influenza, Human/drug therapy ; Pandemics ; RNA, Viral ; SARS-CoV-2 ; Virus Replication |
| Chemical Substances | Antiviral Agents ; RAPGEF3 protein, human ; RNA, Viral ; EPAC1 inhibitor AM-001 |
| Language | English |
| Publishing date | 2023-01-23 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2516098-9 |
| ISSN | 1999-4915 ; 1999-4915 |
| ISSN (online) | 1999-4915 |
| ISSN | 1999-4915 |
| DOI | 10.3390/v15020319 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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