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10.3390/v13061179

http://scihub22266oqcxt.onion/10.3390/v13061179
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34205489!8233786!34205489
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suck abstract from ncbi


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pmid34205489      Viruses 2021 ; 13 (6): ä
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  • Broad Impact of Exchange Protein Directly Activated by cAMP 2 (EPAC2) on Respiratory Viral Infections #MMPMID34205489
  • Choi EJ; Wu W; Cong X; Zhang K; Luo J; Ye S; Wang P; Suresh A; Ullah UM; Zhou J; Bao X
  • Viruses 2021[Jun]; 13 (6): ä PMID34205489show ga
  • The recently discovered exchange protein directly activated by cAMP (EPAC), compared with protein kinase A (PKA), is a fairly new family of cAMP effectors. Soon after the discovery, EPAC has shown its significance in many diseases including its emerging role in infectious diseases. In a recent study, we demonstrated that EPAC, but not PKA, is a promising therapeutic target to regulate respiratory syncytial virus (RSV) replication and its associated inflammation. In mammals, there are two isoforms of EPAC-EPAC1 and EPAC2. Unlike other viruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) and Ebola virus, which use EPAC1 to regulate viral replication, RSV uses EPAC2 to control its replication and associated cytokine/chemokine responses. To determine whether EPAC2 protein has a broad impact on other respiratory viral infections, we used an EPAC2-specific inhibitor, MAY0132, to examine the functions of EPAC2 in human metapneumovirus (HMPV) and adenovirus (AdV) infections. HMPV is a negative-sense single-stranded RNA virus belonging to the family Pneumoviridae, which also includes RSV, while AdV is a double-stranded DNA virus. Treatment with an EPAC1-specific inhibitor was also included to investigate the impact of EPAC1 on these two viruses. We found that the replication of HMPV, AdV, and RSV and the viral-induced immune mediators are significantly impaired by MAY0132, while an EPAC1-specific inhibitor, CE3F4, does not impact or slightly impacts, demonstrating that EPAC2 could serve as a novel common therapeutic target to control these viruses, all of which do not have effective treatment and prevention strategies.
  • |*Virus Replication[MESH]
  • |A549 Cells[MESH]
  • |Adenoviridae/*physiology[MESH]
  • |Cell Line[MESH]
  • |Chemokines/immunology[MESH]
  • |Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism[MESH]
  • |Epithelial Cells/drug effects/virology[MESH]
  • |Guanine Nucleotide Exchange Factors/antagonists & inhibitors/*genetics/*metabolism[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Metapneumovirus/*physiology[MESH]
  • |Quinolines/pharmacology[MESH]


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