{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T17:12:20Z","timestamp":1781025140066,"version":"3.54.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Despite the significant progress achieved in understanding the pathology and clinical management of SARS-CoV-2 infection, still pathogenic and clinical issues need to be clarified. Treatment with modulators of epigenetic targets, i.e., epidrugs, is a current therapeutic option in several cancers and could represent an approach in the therapy of viral diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Aim of this study was the analysis of the role of histone deacetylase (HDAC) inhibition in the modulation of SARS-CoV-2 infection of mesothelial cells (MCs).<\/jats:p><jats:p>MeT5A cells, a pleura MC line, were pre-treated with different specific class I and IIb HDAC inhibitors. Unexpectedly, treatment with HDAC1-3 inhibitors significantly increased ACE2\/TMPRSS2 expression, suggesting a role in favoring SARS-CoV-2 infection. We focused our analysis on the most potent ACE2\/TMPRSS2 inducer among the inhibitors analysed, MS-275, a HDAC1-3 inhibitor. ACE2\/TMPRSS2 expression was validated by Western Blot (WB) and immunofluorescence. The involvement of HDAC inhibition in receptor induction was confirmed by HDAC1\/HDAC2 silencing. In accordance to the ACE2\/TMPRSS2 expression data, MS-275 increased SARS-CoV-2 replication and virus propagation in Vero E6 cells.<\/jats:p><jats:p>Notably, MS-275 was able to increase ACE2\/TMPRSS2 expression and SARS-CoV-2 production, although to a lesser extent, also in the lung adenocarcinoma cell line Calu-3 cells.<\/jats:p><jats:p>Mechanistically, treatment with MS-275 increased H3 and H4 histone acetylation at ACE2\/TMPRSS2 promoters, increasing their transcription.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study highlights a previously unrecognized effect of HDAC1-3 inhibition in increasing SARS-CoV-2 cell entry, replication and productive infection correlating with increased expression of ACE2 and TMPRSS2. These data, while adding basic insight into COVID-19 pathogenesis, warn for the use of HDAC inhibitors in SARS-CoV-2 patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2023.1257683","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T16:49:15Z","timestamp":1702486155000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["HDAC1-3 inhibition increases SARS-CoV-2 replication and productive infection in lung mesothelial and epithelial cells"],"prefix":"10.3389","volume":"13","author":[{"given":"Flavia","family":"Trionfetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonino","family":"Alonzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Bontempi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Terri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Battistelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Montaldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Repele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dante","family":"Rotili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Valente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Zwergel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Matusali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Maggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"Goletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Tripodi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Mai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Strippoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1244556","article-title":"Initial immune response after exposure to Mycobacterium tuberculosis or to SARS-COV-2: similarities and differences","volume":"14","author":"Aiello","year":"2023","journal-title":"Front. Immunol."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11010052","article-title":"Cysteamine with in vitro antiviral activity and immunomodulatory effects has the potential to be a repurposing drug candidate for COVID-19 therapy","volume":"11","author":"Alonzi","year":"2021","journal-title":"Cells"},{"key":"B3","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/s41420-022-01080-8","article-title":"Cysteamine exerts in vitro antiviral activity against the SARS-CoV-2 Delta and Omicron variants","volume":"8","author":"Alonzi","year":"2022","journal-title":"Cell Death Discovery"},{"key":"B4","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/s41591-020-0820-9","article-title":"The proximal origin of SARS-CoV-2","volume":"26","author":"Andersen","year":"2020","journal-title":"Nat. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1038\/leu.2008.9","article-title":"A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas","volume":"22","author":"Balasubramanian","year":"2008","journal-title":"Leukemia"},{"key":"B6","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/onc.2016.260","article-title":"The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition","volume":"36","author":"Battistelli","year":"2017","journal-title":"Oncogene"},{"key":"B7","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/s41419-022-05398-0","article-title":"Restoration of WT1\/miR-769-5p axis by HDAC1 inhibition promotes MMT reversal in mesenchymal-like mesothelial cells","volume":"13","author":"Bontempi","year":"2022","journal-title":"Cell Death Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"10842","DOI":"10.1021\/ja102758v","article-title":"Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A","volume":"132","author":"Butler","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1007\/s40265-020-01421-w","article-title":"Immune therapy, or antiviral therapy, or both for COVID-19: A systematic review","volume":"80","author":"Cantini","year":"2020","journal-title":"Drugs"},{"key":"B10","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1126\/science.abd2985","article-title":"Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity","volume":"370","author":"Cantuti-Castelvetri","year":"2020","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.chom.2020.06.021","article-title":"Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-coV-2 and a clinical isolate of SARS-coV-2","volume":"28","author":"Case","year":"2020","journal-title":"Cell Host Microbe"},{"key":"B12","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1136\/gutjnl-2021-324280","article-title":"Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19","volume":"71","author":"Cheung","year":"2022","journal-title":"Gut"},{"key":"B13","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1042\/CS20130291","article-title":"Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress","volume":"126","author":"Clarke","year":"2014","journal-title":"Clin. Sci. (Lond)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.2217\/fon-2016-0526","article-title":"Entinostat: a promising treatment option for patients with advanced breast cancer","volume":"13","author":"Connolly","year":"2017","journal-title":"Future Oncol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"105357","DOI":"10.1016\/j.meegid.2022.105357","article-title":"Epigenetic mechanisms and host factors impact ACE2 gene expression: Implications in COVID-19 susceptibility","volume":"104","author":"Daniel","year":"2022","journal-title":"Infect. Genet. Evol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s15010-023-02017-8","article-title":"Epigenetic perspectives associated with COVID-19 infection and related cytokine storm: an updated review","author":"Dey","year":"2023","journal-title":"Infection"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2533\/chimia.2022.448","article-title":"Current HDAC inhibitors in clinical trials","volume":"76","author":"Di Bello","year":"2022","journal-title":"Chimia"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1111\/febs.15750","article-title":"Clinical advances in targeting epigenetics for cancer therapy","volume":"289","author":"Feng","year":"2022","journal-title":"FEBS J."},{"key":"B19","doi-asserted-by":"publisher","first-page":"199","DOI":"10.2174\/156800911794328510","article-title":"Epigenetic regulation of gene expression as an anticancer drug target","volume":"11","author":"Ferguson","year":"2011","journal-title":"Curr. Cancer Drug Targets"},{"key":"B20","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1158\/2326-6066.CIR-21-0675","article-title":"Immune-guided therapy of COVID-19","volume":"10","author":"Ferraccioli","year":"2022","journal-title":"Cancer Immunol. Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"111","DOI":"10.3892\/ijo.2011.1014","article-title":"Histone deacetylase inhibitors, valproic acid and trichostatin-A induce apoptosis and affect acetylation status of p53 in ERG-positive prostate cancer cells","volume":"39","author":"Fortson","year":"2011","journal-title":"Int. J. Oncol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1158\/1535-7163.MCT-07-2026","article-title":"MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo","volume":"7","author":"Fournel","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejca.2020.05.027","article-title":"Anticancer drugs and COVID-19 antiviral treatments in patients with cancer: What can we safely use","volume":"136","author":"Gougis","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"B24","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/s41586-020-03148-w","article-title":"Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia","volume":"590","author":"Grant","year":"2021","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","first-page":"5151","DOI":"10.1038\/s41467-021-25393-x","article-title":"Tumour-targeted interleukin-12 and entinostat combination therapy improves cancer survival by reprogramming the tumour immune cell landscape","volume":"12","author":"Hicks","year":"2021","journal-title":"Nat. Commun."},{"key":"B26","doi-asserted-by":"publisher","first-page":"12460","DOI":"10.1021\/acs.jmedchem.0c00830","article-title":"Thirty years of HDAC inhibitors: 2020 insight and hindsight","volume":"63","author":"Ho","year":"2020","journal-title":"J. Med. Chem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-coV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"B28","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-coV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1042\/BJ20070779","article-title":"Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors","volume":"409","author":"Khan","year":"2008","journal-title":"Biochem. J."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1038\/s41416-018-0072-3","article-title":"Suppression of TGFbeta-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition","volume":"118","author":"Kim","year":"2018","journal-title":"Br. J. Cancer"},{"key":"B31","doi-asserted-by":"publisher","first-page":"eabq1366","DOI":"10.1126\/scisignal.abq1366","article-title":"Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release","volume":"16","author":"Labzin","year":"2023","journal-title":"Sci. Signal"},{"key":"B32","doi-asserted-by":"publisher","first-page":"469","DOI":"10.4103\/0973-1482.137937","article-title":"Epigenetic therapy of cancer with histone deacetylase inhibitors","volume":"10","author":"Lakshmaiah","year":"2014","journal-title":"J. Cancer Res. Ther."},{"key":"B33","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s40249-020-00662-x","article-title":"Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues","volume":"9","author":"Li","year":"2020","journal-title":"Infect. Dis. Poverty"},{"key":"B34","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1016\/j.bbrc.2020.04.010","article-title":"EZH2-mediated H3K27me3 inhibits ACE2 expression","volume":"526","author":"Li","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B35","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jim.2012.12.010","article-title":"Development of an enzymatic assay for the detection of neutralizing antibodies against therapeutic angiotensin-converting enzyme 2 (ACE2)","volume":"389","author":"Liao","year":"2013","journal-title":"J. Immunol. Methods"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1021\/acsptsci.0c00163","article-title":"Clinical HDAC inhibitors are effective drugs to prevent the entry of SARS-coV2","volume":"3","author":"Liu","year":"2020","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"307","DOI":"10.2217\/epi.10.7","article-title":"Small-molecule chromatin-modifying agents: therapeutic applications","volume":"2","author":"Mai","year":"2010","journal-title":"Epigenomics"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.752616","article-title":"Pleural mesothelial cells modulate the inflammatory\/profibrotic response during SARS-coV-2 infection","volume":"8","author":"Matusali","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1002\/cam4.3337","article-title":"Class I histone deacetylase inhibition promotes CD8 T cell activation in ovarian cancer","volume":"10","author":"McCaw","year":"2021","journal-title":"Cancer Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1136\/thoraxjnl-2021-217031","article-title":"Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length","volume":"76","author":"McGroder","year":"2021","journal-title":"Thorax"},{"key":"B41","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/j.cell.2020.04.004","article-title":"Inhibition of SARS-coV-2 infections in engineered human tissues using clinical-grade soluble human ACE2","volume":"181","author":"Monteil","year":"2020","journal-title":"Cell"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202115230","article-title":"Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants","volume":"14","author":"Monteil","year":"2022","journal-title":"EMBO Mol. Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"8856018","DOI":"10.1155\/2021\/8856018","article-title":"In vitro models for studying entry, tissue tropism, and therapeutic approaches of highly pathogenic coronaviruses","author":"Najafi Fard","year":"2021","journal-title":"BioMed. Res. Int"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.4155\/fmc-2016-0073","article-title":"MC1568 inhibits HDAC6\/8 activity and influenza A virus replication in lung epithelial cells: role of Hsp90 acetylation","volume":"8","author":"Panella","year":"2016","journal-title":"Future Med. Chem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1093\/infdis\/jiaa332","article-title":"ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19","volume":"222","author":"Pinto","year":"2020","journal-title":"J. Infect. Dis."},{"key":"B46","doi-asserted-by":"publisher","first-page":"173988","DOI":"10.1016\/j.ejphar.2021.173988","article-title":"Potential repurposing of the HDAC inhibitor valproic acid for patients with COVID-19","volume":"898","author":"Pitt","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"112095","DOI":"10.1016\/j.biopha.2021.112095","article-title":"Factors regulating dynamics of angiotensin-converting enzyme-2 (ACE2), the gateway of SARS-CoV-2: Epigenetic modifications and therapeutic interventions by epidrugs","volume":"143","author":"Rath","year":"2021","journal-title":"BioMed. Pharmacother."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.841716","article-title":"HDAC inhibition as potential therapeutic strategy to restore the deregulated immune response in severe COVID-19","volume":"13","author":"Ripamonti","year":"2022","journal-title":"Front. Immunol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"8492","DOI":"10.1038\/s41598-018-26319-2","article-title":"HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal","volume":"8","author":"Rossi","year":"2018","journal-title":"Sci. Rep."},{"key":"B50","doi-asserted-by":"publisher","first-page":"4592","DOI":"10.1073\/pnas.96.8.4592","article-title":"A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors","volume":"96","author":"Saito","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B51","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/s13148-021-01168-5","article-title":"Epigenetic targeting of the ACE2 and NRP1 viral receptors limits SARS-CoV-2 infectivity","volume":"13","author":"Saiz","year":"2021","journal-title":"Clin. Epigenet."},{"key":"B52","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1139\/gen-2020-0135","article-title":"Epigenetic mechanisms influencing COVID-19","volume":"64","author":"Sen","year":"2021","journal-title":"Genome"},{"key":"B53","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/s41392-022-00919-x","article-title":"ACE2-independent infection of T lymphocytes by SARS-CoV-2","volume":"7","author":"Shen","year":"2022","journal-title":"Signal Transduct Target Ther."},{"key":"B54","doi-asserted-by":"publisher","first-page":"428","DOI":"10.2174\/1568009620666201207145019","article-title":"Expression and clinical significance of SARS-coV-2 human targets in neoplastic and non-neoplastic lung tissues","volume":"21","author":"Subbarayan","year":"2021","journal-title":"Curr. Cancer Drug Targets"},{"key":"B55","doi-asserted-by":"publisher","first-page":"3001","DOI":"10.1021\/jm980565u","article-title":"Synthesis and histone deacetylase inhibitory activity of new benzamide derivatives","volume":"42","author":"Suzuki","year":"1999","journal-title":"J. Med. Chem."},{"key":"B56","doi-asserted-by":"publisher","first-page":"3379","DOI":"10.1038\/s41598-021-82970-2","article-title":"Histone deacetylase inhibitors suppress ACE2 and ABO simultaneously, suggesting a preventive potential against COVID-19","volume":"11","author":"Takahashi","year":"2021","journal-title":"Sci. Rep."},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.607204","article-title":"Mechanisms of peritoneal fibrosis: focus on immune cells-peritoneal stroma interactions","volume":"12","author":"Terri","year":"2021","journal-title":"Front. Immunol."},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065763","article-title":"Novel aspects of the immune response involved in the peritoneal damage in chronic kidney disease patients under dialysis","volume":"24","author":"Trionfetti","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41421-021-00279-w","article-title":"Targeting novel LSD1-dependent ACE2 demethylation domains inhibits SARS-CoV-2 replication","volume":"7","author":"Tu","year":"2021","journal-title":"Cell Discovery"},{"key":"B60","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"B61","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41392-021-00679-0","article-title":"The signal pathways and treatment of cytokine storm in COVID-19","volume":"6","author":"Yang","year":"2021","journal-title":"Signal Transduct Target Ther."},{"key":"B62","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s11684-020-0754-0","article-title":"Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection","volume":"14","author":"Zou","year":"2020","journal-title":"Front. Med."},{"key":"B63","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1517\/17460441.2015.1038236","article-title":"Emerging approaches for histone deacetylase inhibitor drug discovery","volume":"10","author":"Zwergel","year":"2015","journal-title":"Expert Opin. Drug Discovery"},{"key":"B64","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1002\/cmdc.202000854","article-title":"Novel pyridine-based hydroxamates and 2\u2019-aminoanilides as histone deacetylase inhibitors: biochemical profile and anticancer activity","volume":"16","author":"Zwergel","year":"2021","journal-title":"ChemMedChem"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1257683\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T16:49:19Z","timestamp":1702486159000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1257683\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,13]]},"references-count":64,"alternative-id":["10.3389\/fcimb.2023.1257683"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1257683","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,13]]},"article-number":"1257683"}}