{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:03:32Z","timestamp":1774857812300,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease pandemic. The virus primarily spreads through person-to-person contact via aerosols and droplets, contributing to high case numbers and related morbidities. SARS-CoV-2 targets the respiratory tract, causing acute respiratory distress syndrome, particularly in immunocompromised individuals such as those with cystic fibrosis (CF). CF is a life-threatening genetic disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, leading to impaired respiratory function and recurrent severe respiratory symptoms. Despite their potential vulnerability, CF patients have shown a lower incidence of severe COVID-19, suggesting protective factors against SARS-CoV-2. Differential expression of the ACE2 receptor, crucial for viral entry, and other host factors, such as TMPRSS2, may play a role in this resistance to SARS-CoV-2. Analyzing the genomics and transcriptomics profiles of CF patients could provide insights into potential resistance mechanisms. The potential resistance mechanisms include blood and extracellular ATP levels, a deleted\/dysfunctional CFTR gene, ACE and ACE2 regulation and expression, ACE and ACE2 polymorphism effects, host proteins and SARS-CoV-2 interactions, and SMN1 and ACE\/ACE2 interactions. This review discusses the underlying factors and potential resistance mechanisms contributing to CF patients\u2019 responses to SARS-CoV-2 infection. The review provides an opportunity to further investigate future therapy and research through understanding the underlying potential resistance mechanisms exhibited by CF patients against SARS-CoV-2, including ACE and ACE2 polymorphisms.<\/jats:p>","DOI":"10.3390\/v17070919","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"919","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Potential Resistance Mechanisms Exhibited by Cystic Fibrosis Patients Against SARS-CoV-2"],"prefix":"10.3390","volume":"17","author":[{"given":"Yasmin K.","family":"Elsharabassi","sequence":"first","affiliation":[{"name":"Basic Medical Sciences Department, College of Medicine, QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuha T.","family":"Swaidan","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences Department, College of Medicine, QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed M.","family":"Emara","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences Department, College of Medicine, QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100618","DOI":"10.1016\/j.cpcardiol.2020.100618","article-title":"COVID-19 and Multiorgan Response","volume":"45","author":"Zaim","year":"2020","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108448","DOI":"10.1016\/j.clim.2020.108448","article-title":"COVID-19: Immunology and treatment options","volume":"215","author":"Felsenstein","year":"2020","journal-title":"Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1021\/acs.molpharmaceut.0c00608","article-title":"COVID-19 Transmission, Current Treatment, and Future Therapeutic Strategies","volume":"18","author":"Salian","year":"2021","journal-title":"Mol. Pharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/d41573-020-00073-5","article-title":"The COVID-19 vaccine development landscape","volume":"19","author":"Andreadakis","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.jpeds.2016.09.064","article-title":"Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation","volume":"181","author":"Farrell","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s40248-019-0193-4","article-title":"Approaching two decades of cystic fibrosis research in Qatar: A historical perspective and future directions","volume":"14","author":"Hammoudeh","year":"2019","journal-title":"Multidiscip. Respir. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.5339\/qmj.2020.4","article-title":"CT score and correlation with lung function and microbiology of adult patients with cystic fibrosis with predominant I1234V genotype in Qatar","volume":"2020","author":"Thomas","year":"2020","journal-title":"Qatar. Med. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1152\/physrev.1999.79.1.S3","article-title":"Physiological Basis of Cystic Fibrosis: A Historical Perspective","volume":"79","author":"Quinton","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1016\/S2213-2600(20)30177-6","article-title":"Impact of COVID-19 on people with cystic fibrosis","volume":"8","author":"Colombo","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_10","first-page":"100268","article-title":"COVID-19: Pathophysiology and implications for cystic fibrosis, diabetes and cystic fibrosis-related diabetes","volume":"26","author":"Mason","year":"2021","journal-title":"J. Clin. Transl. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"19","DOI":"10.5339\/qmj.2023.19","article-title":"The clinical features and impact of SARS-CoV-2\/COVID-19 infection in children with Cystic Fibrosis (CF): A Qatari experience","volume":"2023","author":"Hamad","year":"2023","journal-title":"Qatar. Med. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jcf.2011.06.004","article-title":"Impact of the A (H1N1) pandemic influenza (season 2009\u20132010) on patients with cystic fibrosis","volume":"10","author":"Viviani","year":"2011","journal-title":"J. Cyst. Fibros."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kiedrowski, M.R., and Bomberger, J.M. (2018). Viral-Bacterial Co-infections in the Cystic Fibrosis Respiratory Tract. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.03067"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1183\/09031936.00228013","article-title":"CFTR: Cystic fibrosis and beyond","volume":"44","author":"Mall","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nrg3849","article-title":"Cystic fibrosis genetics: From molecular understanding to clinical application","volume":"16","author":"Cutting","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.jcf.2019.11.003","article-title":"The genetics and genomics of cystic fibrosis","volume":"19","author":"Sharma","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s40142-019-00174-7","article-title":"An Overview of the Homozygous Cystic Fibrosis Transmembrane Conductance Regulator Mutation c.3700 A>G (p.Ile1234Val) in Qatar","volume":"7","author":"Hammoudeh","year":"2019","journal-title":"Curr. Genet. Med. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1091\/mbc.e14-04-0935","article-title":"From CFTR biology toward combinatorial pharmacotherapy: Expanded classification of cystic fibrosis mutations","volume":"27","author":"Veit","year":"2016","journal-title":"Mol. Biol. Cell."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3390\/arm92040026","article-title":"Cystic Fibrosis: Understanding Cystic Fibrosis Transmembrane Regulator Mutation Classification and Modulator Therapies","volume":"92","author":"Anwar","year":"2024","journal-title":"Adv. Respir. Med."},{"key":"ref_20","unstructured":"Hodson, M., Andrew, B., and Duncan, G. (2012). Cystic Fibrosis, CRC Press."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jcf.2005.05.011","article-title":"Viral respiratory infections in cystic fibrosis","volume":"4","author":"Wolfs","year":"2005","journal-title":"J. Cyst. Fibros."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1128\/CMR.15.2.194-222.2002","article-title":"Lung infections associated with cystic fibrosis","volume":"15","author":"Lyczak","year":"2002","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/(SICI)1099-0496(199812)26:6<371::AID-PPUL1>3.0.CO;2-N","article-title":"Severe Viral Respiratory Infections in Infants with Cystic Fibrosis","volume":"26","author":"Armstrong","year":"1998","journal-title":"Pediatr. Pulmonol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.jcf.2019.02.004","article-title":"Early respiratory viral infections in infants with cystic fibrosis","volume":"18","author":"Deschamp","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"399","DOI":"10.7883\/yoken.67.399","article-title":"Human Rhinovirus Infection in Children with Cystic Fibrosis [Internet]","volume":"67","author":"Esposito","year":"2014","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1136\/thoraxjnl-2013-204000","article-title":"Incidence and clinical impact of respiratory viruses in adults with cystic fibrosis","volume":"69","author":"Flight","year":"2014","journal-title":"Thorax"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ling, K.-M., Garratt, L.W., Gill, E.E., Lee, A.H.Y., Agudelo-Romero, P., Sutanto, E.N., Iosifidis, T., Rosenow, T., Turvey, S.E., and Lassmann, T. (2020). Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children with Cystic Fibrosis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01327"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1128\/CMR.13.3.371","article-title":"Respiratory Syncytial Virus Infection in Adults","volume":"13","author":"Falsey","year":"2000","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/ppul.20751","article-title":"Prophylaxis against respiratory syncytial virus in young children with cystic fibrosis","volume":"43","author":"Giebels","year":"2008","journal-title":"Pediatr. Pulmonol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1055\/s-0036-1584801","article-title":"Human Influenza Virus Infections","volume":"37","author":"Peteranderl","year":"2016","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Renk, H., Regamey, N., and Hartl, D. (2014). Influenza a(H1N1)pdm09 and cystic fibrosis lung disease: A systematic meta-analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0078583"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1093\/cid\/cix203","article-title":"Cystic fibrosis pulmonary exacerbations attributable to respiratory syncytial virus and influenza: A population-based study","volume":"64","author":"Somayaji","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1055\/s-0036-1584798","article-title":"Parainfluenza Virus Infection","volume":"37","author":"Branche","year":"2016","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11882-017-0685-2","article-title":"The Role of Human Parainfluenza Virus Infections in the Immunopathology of the Respiratory Tract","volume":"17","author":"Kowalski","year":"2017","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Terlizzi, V., Motisi, M.A., Pellegrino, R., Padoan, R., and Chiappini, E. (2022). Risk factors for severe COVID-19 in people with cystic fibrosis: A systematic review. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.958658"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1097\/JCMA.0000000000000270","article-title":"The outbreak of COVID-19: An overview","volume":"83","author":"Wu","year":"2020","journal-title":"J. Chin. Med. Assoc."},{"key":"ref_37","first-page":"100403","article-title":"Estimated SARS-CoV-2 antibody seroprevalence trends and relationship to reported case prevalence from a repeated, cross-sectional study in the 50 states and the District of Columbia, United States\u201425 October 2020\u201326 February 2022","volume":"18","author":"Wiegand","year":"2023","journal-title":"Lancet Reg. Health\u2013Am."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"254.e1","DOI":"10.1016\/j.cmi.2022.07.005","article-title":"Exhaled SARS-CoV-2 RNA viral load kinetics measured by facemask sampling associates with household transmission","volume":"29","author":"Pan","year":"2023","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2021.01.007","article-title":"Adaptive immunity to SARS-CoV-2 and COVID-19","volume":"184","author":"Sette","year":"2021","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Monteiro, M.E.S., Lechuga, G.C., Napole\u00e3o-P\u00eago, P., Carvalho, J.P.R.S., Gomes, L.R., Morel, C.M., Provance, D.W., and De-Simone, S.G. (2024). Humoral Immune Response to SARS-CoV-2 Spike Protein Receptor-Binding Motif Linear Epitopes. Vaccines, 12.","DOI":"10.20944\/preprints202402.0093.v1"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"101122","DOI":"10.1016\/j.genrep.2021.101122","article-title":"An overview of basic molecular biology of SARS-CoV-2 and current COVID-19 prevention strategies","volume":"23","author":"Das","year":"2021","journal-title":"Gene Rep."},{"key":"ref_42","unstructured":"World Health Organization (WHO) [Internet] (2025, June 16). Tracking SARS-CoV-2 Variants, Available online: https:\/\/www.who.int\/activities\/tracking-SARS-CoV-2-variants\/2020-DON305."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chen, L., He, Y., Liu, H., Shang, Y., and Guo, G. (2024). Potential immune evasion of the severe acute respiratory syndrome coronavirus 2 Omicron variants. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1339660"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chatterjee, S., Bhattacharya, M., Nag, S., Dhama, K., and Chakraborty, C. (2023). A Detailed Overview of SARS-CoV-2 Omicron: Its Sub-Variants, Mutations and Pathophysiology, Clinical Characteristics, Immunological Landscape, Immune Escape, and Therapies. Viruses, 15.","DOI":"10.3390\/v15010167"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.cca.2022.11.017","article-title":"COVID-19 diagnostics: Molecular biology to nanomaterials","volume":"538","author":"Perveen","year":"2023","journal-title":"Clin. Chim. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1165\/rcmb.2024-0213OC","article-title":"Distinct Responses of Cystic Fibrosis Epithelial Cells to SARS-CoV-2 and Influenza A Virus","volume":"72","author":"Pagani","year":"2025","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100073","DOI":"10.1016\/j.sintl.2020.100073","article-title":"Update vision on COVID-19: Structure, immune pathogenesis, treatment and safety assessment","volume":"2","author":"Agrahari","year":"2021","journal-title":"Sens. Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.cytogfr.2020.05.002","article-title":"COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons","volume":"53","author":"Nile","year":"2020","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5338","DOI":"10.1523\/JNEUROSCI.3188-20.2021","article-title":"SARS-CoV-2 Neuronal Invasion and Complications: Potential Mechanisms and Therapeutic Approaches","volume":"41","author":"Swain","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_50","first-page":"1289","article-title":"Virus entry at a glance","volume":"16","author":"Yamauchi","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0065-3527(08)60583-7","article-title":"Virus Entry into Animal Cells","volume":"36","author":"Marsh","year":"1989","journal-title":"Adv. Virus Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41467-023-35862-0","article-title":"SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation","volume":"14","author":"Bezzerri","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Falcone, C., Caracciolo, M., Correale, P., Macheda, S., Vadal\u00e0, E.G., La Scala, S., Tescione, M., Danieli, R., Ferrarelli, A., and Tarsitano, M.G. (2020). Can adenosine fight COVID-19 acute respiratory distress syndrome?. J. Clin. Med., 9.","DOI":"10.20944\/preprints202007.0426.v1"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.4049\/jimmunol.1700187","article-title":"Virus-Triggered ATP Release Limits Viral Replication through Facilitating IFN-\u03b2 Production in a P2X7-Dependent Manner","volume":"199","author":"Zhang","year":"2017","journal-title":"J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s11302-021-09771-0","article-title":"Cystic fibrosis improves COVID-19 survival and provides clues for treatment of SARS-CoV-2","volume":"17","author":"Abraham","year":"2021","journal-title":"Purinergic Signal"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lotti, V., Merigo, F., Lagni, A., Di Clemente, A., Ligozzi, M., Bernardi, P., Rossini, G., Concia, E., Plebani, R., and Romano, M. (2022). CFTR Modulation Reduces SARS-CoV-2 Infection in Human Bronchial Epithelial Cells. Cells, 11.","DOI":"10.3390\/cells11081347"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Colombo, C., Alicandro, G., Dacc\u00f3, V., Gagliano, V., Morlacchi, L.C., Casciaro, R., Pisi, G., Francalanci, M., Badolato, R., and Bignamini, E. (2021). SARS-CoV-2 infection in cystic fibrosis: A multicentre prospective study with a control group, Italy, February-July 2020. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251527"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Mathew, H.R., Choi, M.Y., Parkins, M.D., and Fritzler, M.J. (2021). Systematic review: Cystic fibrosis in the SARS-CoV-2\/COVID-19 pandemic. BMC Pulm. Med., 21.","DOI":"10.1186\/s12890-021-01528-0"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12462","DOI":"10.12998\/wjcc.v10.i34.12470","article-title":"Circulating angiotensin converting enzyme 2 and COVID-19","volume":"10","author":"Leowattana","year":"2022","journal-title":"World J. Clin. Cases"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1124\/molpharm.120.000119","article-title":"Dysregulation of angiotensin converting enzyme 2 expression and function in comorbid disease conditions possibly contributes to coronavirus infectious disease 2019 complication severity","volume":"99","author":"Hammoud","year":"2021","journal-title":"Mol. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.jinf.2022.06.030","article-title":"Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection","volume":"85","author":"Gao","year":"2022","journal-title":"J. Infect."},{"key":"ref_62","doi-asserted-by":"crossref","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":"ref_63","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1152\/ajplung.00225.2020","article-title":"SARS-CoV-2 (COVID-19) and cystic fibrosis","volume":"319","author":"Stanton","year":"2020","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"104773","DOI":"10.1016\/j.meegid.2021.104773","article-title":"Variants in ACE2; potential influences on virus infection and COVID-19 severity","volume":"90","author":"Bakhshandeh","year":"2021","journal-title":"Infect. Genet. Evol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ali, F., Elserafy, M., Alkordi, M.H., and Amin, M. (2020). ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity. Biochem. Biophys. Rep., 24.","DOI":"10.1016\/j.bbrep.2020.100798"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.biochi.2020.11.004","article-title":"Molecular docking simulation reveals ACE2 polymorphisms that may increase the affinity of ACE2 with the SARS-CoV-2 Spike protein","volume":"180","author":"Calcagnile","year":"2021","journal-title":"Biochimie"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"145102","DOI":"10.1016\/j.gene.2020.145102","article-title":"Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 outcome","volume":"762","author":"Albaiceta","year":"2020","journal-title":"Gene"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1159\/000533606","article-title":"TGF-\u03b21 Inhibition of ACE2 Mediated by miRNA Uncovers Novel Mechanism of SARS-CoV-2 Pathogenesis","volume":"15","author":"Hejenkowska","year":"2023","journal-title":"J. Innate Immun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1186\/s13054-020-03120-0","article-title":"Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19","volume":"24","author":"Ni","year":"2020","journal-title":"Crit. Care"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1186\/s12967-021-03168-8","article-title":"Multi-omics approach to COVID-19: A domain-based literature review","volume":"19","author":"Montaldo","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/s41419-021-03881-8","article-title":"Looking for pathways related to COVID-19: Confirmation of pathogenic mechanisms by SARS-CoV-2\u2013host interactome","volume":"12","author":"Messina","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"St-Germain, J.R., Astori, A., Samavarchi-Tehrani, P., Abdouni, H., Macwan, V., Kim, D.-K., Knapp, J.J., Roth, F.P., Gingras, A.-C., and Raught, B. (2020). A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: New proteomics resources for COVID-19 research [Internet]. bioRxiv.","DOI":"10.1101\/2020.08.28.269175"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1006\/cyto.2002.1047","article-title":"Downregulation of angiotensin converting enzyme by TNF-\u03b1 in differentiating human macrophages","volume":"18","author":"Viinikainen","year":"2002","journal-title":"Cytokine"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Marson, F.A.L., Bertuzzo, C.S., Hortencio, T.D.R., Ribeiro, J.D., Bonadia, L.C., and Ribeiro, A.F. (2012). The ACE gene D\/I polymorphism as a modulator of severity of cystic fibrosis. BMC Pulm. Med., 12.","DOI":"10.1186\/1471-2466-12-41"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1093\/bib\/bbaa285","article-title":"Bioinformatic analysis of SMN1-ACE\/ACE2 interactions hinted at a potential protective effect of spinal muscular atrophy against COVID-19-induced lung injury","volume":"22","author":"Li","year":"2021","journal-title":"Brief. Bioinform."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.bbamcr.2017.02.011","article-title":"SMN1 functions as a novel inhibitor for TRAF6-mediated NF-\u03baB signaling","volume":"1864","author":"Kim","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell. Res."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/7\/919\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:37Z","timestamp":1760032837000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/7\/919"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":76,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["v17070919"],"URL":"https:\/\/doi.org\/10.3390\/v17070919","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]}}}