{"doi":"10.3390/v13061179","title":"Broad Impact of Exchange Protein Directly Activated by cAMP 2 (EPAC2) on Respiratory Viral Infections","abstract":"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.","journal":"Viruses","year":2021,"id":202540,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":326646,"name":"Wenzhe Wu","orcid":"0000-0002-8030-3698","position":1,"is_corresponding":false},{"id":783210,"name":"Xiaoyan Cong","orcid":null,"position":2,"is_corresponding":false},{"id":782629,"name":"Ke Zhang","orcid":"0000-0001-6777-6290","position":3,"is_corresponding":false},{"id":782630,"name":"Jiaqi Luo","orcid":"0000-0002-0973-2633","position":4,"is_corresponding":false},{"id":782631,"name":"Sha Ye","orcid":"0000-0001-9788-8250","position":5,"is_corresponding":false},{"id":383917,"name":"Pingyuan Wang","orcid":"0009-0005-0368-5070","position":6,"is_corresponding":false},{"id":783211,"name":"Adarsh Suresh","orcid":null,"position":7,"is_corresponding":false},{"id":783212,"name":"Uneeb Mohammad Ullah","orcid":null,"position":8,"is_corresponding":false},{"id":107272,"name":"Jia Zhou","orcid":"0000-0002-2811-1090","position":9,"is_corresponding":false},{"id":326649,"name":"Xiaoyong Bao","orcid":"0000-0002-6884-2584","position":10,"is_corresponding":false},{"id":782628,"name":"Eun-Jin Choi","orcid":"0000-0003-3812-4677","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-18T23:51:10.291262Z","pmid":"34205489","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}