{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:12:47Z","timestamp":1760145167334,"version":"build-2065373602"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ASPIRE Precision Medicine Research Institute","award":["VRI-20-10"],"award-info":[{"award-number":["VRI-20-10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>ACE2, part of the angiotensin-converting enzyme family and the renin\u2013angiotensin\u2013aldosterone system (RAAS), plays vital roles in cardiovascular and renal functions. It is also the primary receptor for SARS-CoV-2, enabling its entry into cells. This project aimed to study ACE2\u2019s cellular trafficking and maturation to the cell surface and assess the impact of various drugs and compounds on these processes. We used cellular and biochemical analyses to evaluate these compounds as potential leads for COVID-19 therapeutics. Our screening assay focused on ACE2 maturation levels and subcellular localization with and without drug treatments. Results showed that ACE2 maturation is generally fast and robust, with certain drugs having a mild impact. Out of twenty-three tested compounds, eight significantly reduced ACE2 maturation levels, and three caused approximately 20% decreases. Screening trafficking inhibitors revealed significant effects from most molecular modulators of protein trafficking, mild effects from most proposed COVID-19 drugs, and no effects from statins. This study noted that manipulating ACE2 levels could be beneficial or harmful, depending on the context. Thus, using this approach to uncover leads for COVID-19 therapeutics requires a thorough understanding ACE2\u2019s biogenesis and biology.<\/jats:p>","DOI":"10.3390\/biom14070764","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T13:26:43Z","timestamp":1719494803000},"page":"764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Evaluation of Drugs as Potential Modulators of the Trafficking and Maturation of ACE2, the SARS-CoV-2 Receptor"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1751-5070","authenticated-orcid":false,"given":"Nesreen F.","family":"Alkhofash","sequence":"first","affiliation":[{"name":"Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1306-6618","authenticated-orcid":false,"given":"Bassam R.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab Emirates"},{"name":"ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein","volume":"181","author":"Walls","year":"2020","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"106356","DOI":"10.1016\/j.rmed.2021.106356","article-title":"COVID-19: Why does disease severity vary among individuals?","volume":"180","author":"Samadizadeh","year":"2021","journal-title":"Respir. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41435-020-0107-7","article-title":"Genetic variability in the expression of the SARS-CoV-2 host cell entry factors across populations","volume":"21","author":"Sawalha","year":"2020","journal-title":"Genes Immun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.chom.2020.08.004","article-title":"Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor","volume":"28","author":"Zhao","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40246-021-00304-9","article-title":"ACE2 Nascence, trafficking, and SARS-CoV-2 pathogenesis: The saga continues","volume":"15","author":"Badawi","year":"2021","journal-title":"Hum. Genom."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Samavati, L., and Uhal, B.D. (2020). ACE2, Much More Than Just a Receptor for SARS-COV-2. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00317"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1139\/y02-021","article-title":"ACEH\/ACE2 is a novel mammalian metallocarboxypeptidase and a homologue of angiotensin-converting enzyme insensitive to ACE inhibitors","volume":"80","author":"Turner","year":"2011","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1042\/CS20200419","article-title":"Alternative splicing of ACE2 possibly generates variants that may limit the entry of SARS-CoV-2: A potential therapeutic approach using SSOs","volume":"134","author":"Rehman","year":"2020","journal-title":"Clin. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2012","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nm1267","article-title":"A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus\u2013induced lung injury","volume":"11","author":"Kuba","year":"2005","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/s41586-020-2312-y","article-title":"The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice","volume":"583","author":"Bao","year":"2020","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109721","DOI":"10.1016\/j.cellsig.2020.109721","article-title":"Drugs targeting various stages of the SARS-CoV-2 life cycle: Exploring promising drugs for the treatment of COVID-19","volume":"74","author":"Poduri","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hussain, M., Jabeen, N., Amanullah, A., Baig, A.A., Aziz, B., Shabbir, S., Raza, F., and Uddin, N. (2020). Molecular docking between human TMPRSS2 and SARS-CoV-2 spike protein: Conformation and intermolecular interactions. AIMS Microbiol., 6.","DOI":"10.3934\/microbiol.2020021"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1093\/ibd\/izaa249","article-title":"Unraveling the Role of ACE2, the Binding Receptor for SARS-CoV-2, in Inflammatory Bowel Disease","volume":"26","author":"Estevinho","year":"2020","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1136\/postgradmedj-2020-137935","article-title":"ACE2 and COVID-19 and the resulting ARDS","volume":"96","author":"Zhang","year":"2020","journal-title":"Postgrad. Med. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1177\/2472555220934421","article-title":"Repurposing Nimesulide, a Potent Inhibitor of the B0AT1 Subunit of the SARS-CoV-2 Receptor, as a Therapeutic Adjuvant of COVID-19","volume":"25","author":"Scalise","year":"2020","journal-title":"SLAS Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.2147\/DDDT.S252351","article-title":"ACE2 attenuates epithelial-mesenchymal transition in MLE-12 cells induced by silica","volume":"14","author":"Li","year":"2020","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"30113","DOI":"10.1074\/jbc.M505111200","article-title":"Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2)","volume":"280","author":"Lambert","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"L84","DOI":"10.1152\/ajplung.00071.2009","article-title":"Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia","volume":"297","author":"Hong","year":"2009","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1161\/HYPERTENSIONAHA.114.03743","article-title":"Angiotensin II mediates angiotensin converting enzyme type 2 internalization and degradation through an Angiotensin II type I receptor-dependent mechanism","volume":"64","author":"Deshotels","year":"2014","journal-title":"Hypertension"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"117905","DOI":"10.1016\/j.lfs.2020.117905","article-title":"Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications","volume":"256","author":"Banu","year":"2020","journal-title":"Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s40246-022-00411-1","article-title":"Characterization of ACE2 naturally occurring missense variants: Impact on subcellular localization and trafficking","volume":"16","author":"Badawi","year":"2022","journal-title":"Hum. Genom."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17.13A.1","DOI":"10.1002\/0471142727.mb1713as89","article-title":"Endoglycosidase and Glycoamidase Release of N-Linked Glycans","volume":"89","author":"Freeze","year":"2010","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wu, Z.L., and Ertelt, J.M. (2022). Endoglycosidase assay using enzymatically synthesized fluorophore-labeled glycans as substrates to uncover enzyme substrate specificities. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-03444-3"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1093\/hmg\/ddn354","article-title":"Defective cellular trafficking of missense NPR-B mutants is the major mechanism underlying acromesomelic dysplasia-type Maroteaux","volume":"18","author":"Hume","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ali, B.R., Ben-Rebeh, I., John, A., Akawi, N.A., Milhem, R.M., Al-Shehhi, N.A., Al-Ameri, M.M., Al-Shamisi, S.A., and Al-Gazali, L. (2011). Endoplasmic Reticulum Quality Control Is Involved in the Mechanism of Endoglin-Mediated Hereditary Haemorrhagic Telangiectasia. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026206"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e12928","DOI":"10.1111\/tra.12928","article-title":"Endoglin mutants retained in the endoplasmic reticulum exacerbate loss of function in hereditary hemorrhagic telangiectasia type 1 (HHT1) by exerting dominant negative effects on the wild type allele","volume":"25","author":"Gariballa","year":"2024","journal-title":"Traffic"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.1073\/pnas.0631766100","article-title":"Exo1: A new chemical inhibitor of the exocytic pathway","volume":"100","author":"Feng","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"31087","DOI":"10.1074\/jbc.M806592200","article-title":"A novel small molecule regulator of guanine nucleotide exchange activity of the ADP-ribosylation factor and golgi membrane trafficking","volume":"283","author":"Pan","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/nchembio751","article-title":"Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in vitro","volume":"2","author":"Pelish","year":"2006","journal-title":"Nat. Chem. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41392-021-00584-6","article-title":"Berbamine inhibits SARS-CoV-2 infection by compromising TRPMLs-mediated endolysosomal trafficking of ACE2","volume":"6","author":"Huang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"27911","DOI":"10.1038\/srep27911","article-title":"Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1\/2 and NF-\u03baB signaling pathways","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","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":"ref_35","doi-asserted-by":"crossref","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":"ref_36","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1002\/ddr.21982","article-title":"Celastrol: A lead compound that inhibits SARS-CoV-2 replication, the activity of viral and human cysteine proteases, and virus-induced IL-6 secretion","volume":"83","author":"Fuzo","year":"2022","journal-title":"Drug Dev. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.chembiol.2013.03.019","article-title":"Small molecules CK-666 and CK-869 inhibit actin-related protein 2\/3 complex by blocking an activating conformational change","volume":"20","author":"Hetrick","year":"2013","journal-title":"Chem. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100307","DOI":"10.1016\/j.jve.2022.100307","article-title":"Identification of a pharmacological approach to reduce ACE2 expression and development of an in vitro COVID-19 viral entry model","volume":"8","author":"Endo","year":"2022","journal-title":"J. Virus Erad."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1038\/bjc.2014.519","article-title":"Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo","volume":"111","author":"Schwab","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12047","DOI":"10.1038\/s41598-022-16357-2","article-title":"Protective effects of statins on COVID-19 risk, severity and fatal outcome: A nationwide Swedish cohort study","volume":"12","author":"Santosa","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s12012-021-09674-x","article-title":"Plausible Positive Effects of Statins in COVID-19 Patient","volume":"21","author":"Vitiello","year":"2021","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.atherosclerosis.2021.06.911","article-title":"Statin use and mortality in COVID-19 patients: Updated systematic review and meta-analysis","volume":"330","author":"Kollias","year":"2021","journal-title":"Atherosclerosis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1016\/j.dsx.2020.10.021","article-title":"Statins and SARS-CoV-2 disease: Current concepts and possible benefits","volume":"14","author":"Minz","year":"2020","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"103469","DOI":"10.1016\/j.isci.2021.103469","article-title":"Fluvastatin mitigates SARS-CoV-2 infection in human lung cells","volume":"24","author":"Moeller","year":"2021","journal-title":"iScience"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zhang, Z.R., Zhang, Y.N., Zhang, H.Q., Zhang, Q.Y., Li, N., Li, Q., Deng, C.L., Zhang, B., Li, X.D., and Ye, H.Q. (2022). Berbamine hydrochloride potently inhibits SARS-CoV-2 infection by blocking S protein-mediated membrane fusion. PLoS Negl. Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0010363"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s41061-021-00353-7","article-title":"The Repurposed ACE2 Inhibitors: SARS-CoV-2 Entry Blockers of COVID-19","volume":"379","author":"Ahmad","year":"2021","journal-title":"Top. Curr. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1538\/expanim.17-0053","article-title":"Loss of angiotensin converting enzyme II (ACE2) accelerates the developmentof liver injury induced by thioacetamide","volume":"67","author":"Wu","year":"2018","journal-title":"Exp. Anim."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.phrs.2017.05.008","article-title":"AT1 receptor signaling pathways in the cardiovascular system","volume":"125","author":"Kawai","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ejim.2021.09.007","article-title":"The pivotal link between ACE2 deficiency and SARS-CoV-2 infection: One year later","volume":"93","author":"Angeli","year":"2021","journal-title":"Eur. J. Intern. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jinf.2020.03.005","article-title":"Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients","volume":"80","author":"Liu","year":"2020","journal-title":"J. Infect."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s10238-022-00821-4","article-title":"Comorbidities and clinical complications associated with SARS-CoV-2 infection: An overview","volume":"23","author":"Gupta","year":"2023","journal-title":"Clin. Exp. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"218","DOI":"10.3390\/covid1010018","article-title":"Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis","volume":"1","author":"Yu","year":"2021","journal-title":"COVID"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100941","DOI":"10.1016\/j.eclinm.2021.100941","article-title":"A simple, home-therapy algorithm to prevent hospitalisation for COVID-19 patients: A retrospective observational matched-cohort study","volume":"37","author":"Suter","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.ymthe.2005.03.038","article-title":"Role of Clathrin-and Caveolae-Mediated Endocytosis in Gene Transfer Mediated by Lipo-and Polyplexes","volume":"12","author":"Rejman","year":"2005","journal-title":"Mol. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wang, H., Yuan, Z., Pavel, M.A., Jablonski, S.M., Jablonski, J., Hobson, R., Valente, S., Reddy, C.B., and Hansen, S.B. (2023). The role of high cholesterol in SARS-CoV-2 infectivity. J. Biol. Chem., 299.","DOI":"10.1016\/j.jbc.2023.104763"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"105949","DOI":"10.1016\/j.ijantimicag.2020.105949","article-title":"Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial","volume":"56","author":"Gautret","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1743-422X-2-69","article-title":"Chloroquine is a potent inhibitor of SARS coronavirus infection and spread","volume":"2","author":"Vincent","year":"2005","journal-title":"Virol. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.phrs.2017.06.005","article-title":"The vasoprotective axes of the renin-angiotensin system: Physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases","volume":"125","author":"Li","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1161\/CIRCULATIONAHA.104.510461","article-title":"Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2","volume":"111","author":"Ferrario","year":"2005","journal-title":"Circulation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1093\/eurheartj\/ehi043","article-title":"ACE and ACE2: A tale of two enzymes","volume":"26","author":"Zisman","year":"2005","journal-title":"Eur. Heart J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/aps.2009.80","article-title":"Adenosine A 1 receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro","volume":"30","author":"Xie","year":"2009","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"37052","DOI":"10.1038\/srep37052","article-title":"Bafilomycin A1 induces caspase-independent cell death in hepatocellular carcinoma cells via targeting of autophagy and MAPK pathways","volume":"6","author":"Yan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Chen, Y., Li, M.X., Lu, G.D., Shen, H.M., and Zhou, J. (2021). Hydroxychloroquine\/Chloroquine as Therapeutics for COVID-19: Truth under the Mystery. Int. J. Biol. Sci., 17.","DOI":"10.7150\/ijbs.59547"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4616","DOI":"10.1038\/s41598-019-40851-9","article-title":"In vitro metabolic activation of vitamin D3 by using a multi-compartment microfluidic liver-kidney organ on chip platform","volume":"9","author":"Theobald","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Wu, W., Wang, Y., Deng, X.L., Sun, H.Y., and Li, G.R. (2013). Cholesterol Down-Regulates BK Channels Stably Expressed in HEK 293 Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079952"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1007\/s00432-013-1465-6","article-title":"Belinostat and panobinostat (HDACI): In vitro and in vivo studies in thyroid cancer","volume":"139","author":"Chan","year":"2013","journal-title":"J Cancer Res. Clin. Oncol."},{"key":"ref_67","first-page":"1","article-title":"Nephroprotective activity of Annona Squamosa leaves against paracetamol-induced nephrotoxicity in rats: In vitro and in vivo experiments","volume":"6","author":"Neelima","year":"2020","journal-title":"Future J. Pharm. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Li, L., Sun, Y., Liu, J., Wu, X., Chen, L., Ma, L., and Wu, P. (2015). Histone deacetylase inhibitor sodium butyrate suppresses DNA double strand break repair induced by etoposide more effectively in MCF-7 cells than in HEK293 cells. BMC Biochem., 16.","DOI":"10.1186\/s12858-014-0030-5"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"E11138","DOI":"10.1073\/pnas.1801156115","article-title":"Vorinostat, a pan-HDAC inhibitor, abrogates productive HPV-18 DNA amplification","volume":"115","author":"Banerjee","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/7\/764\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:06:07Z","timestamp":1760108767000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/7\/764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,27]]},"references-count":69,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["biom14070764"],"URL":"https:\/\/doi.org\/10.3390\/biom14070764","relation":{},"ISSN":["2218-273X"],"issn-type":[{"type":"electronic","value":"2218-273X"}],"subject":[],"published":{"date-parts":[[2024,6,27]]}}}