{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:38:08Z","timestamp":1777045088363,"version":"3.51.4"},"reference-count":172,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human ACE2 and the serine protease TMPRSS2 of novel SARS-CoV-2 are primary entry receptors in host cells. Expression of these genes at the transcriptional level has not been much discussed in detail. The ISRE elements of the ACE2 promoter are a binding site for the ISGF3 complex of the JAK\/STAT signaling pathway. TMPRSS2, including IFN\u03b2, STAT1, and STAT2, has the PARP1 binding site near to TSS either up or downstream promoter region. It is well documented that PARP1 regulates gene expression at the transcription level. Therefore, to curb virus infection, both promoting type I IFN signaling to boost innate immunity and prevention of virus entry by inhibiting PARP1, ACE2 or TMPRSS2 are safe options. Most importantly, our aim is to attract the attention of the global scientific community towards the codon 72 Single Nucleotide Polymorphism (SNP) of p53 and its underneath role in the innate immune response against SARS-CoV-2. Here, we discuss codon 72 SNP of human p53\u2032s role in the different innate immune response to restrict virus-mediated mortality rate only in specific parts of the world. In addition, we discuss potential targets and emerging therapies using bioengineered bacteriophage, anti-sense, or CRISPR strategies.<\/jats:p>","DOI":"10.3390\/ijms22168660","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T10:54:41Z","timestamp":1628765681000},"page":"8660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["SARS-CoV-2: Understanding the Transcriptional Regulation of ACE2 and TMPRSS2 and the Role of Single Nucleotide Polymorphism (SNP) at Codon 72 of p53 in the Innate Immune Response against Virus Infection"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5940-2915","authenticated-orcid":false,"given":"Niraj","family":"Lodhi","sequence":"first","affiliation":[{"name":"Clinical Research (Research and Development Division) miRNA Analytics LLC, Harlem Bio-Space, New York, NY 10027, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rubi","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satya","family":"Rajput","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Warwick University, Coventry CV47AL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7030-3777","authenticated-orcid":false,"given":"Quaiser","family":"Saquib","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Sciences, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1126\/science.abb3221","article-title":"Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2)","volume":"368","author":"Li","year":"2020","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.cell.2020.04.021","article-title":"Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States","volume":"181","author":"Fauver","year":"2020","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nature02145","article-title":"Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus","volume":"426","author":"Li","year":"2003","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4122","DOI":"10.1128\/JVI.02232-10","article-title":"Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response","volume":"85","author":"Glowacka","year":"2011","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12658","DOI":"10.1128\/JVI.01542-10","article-title":"Efficient Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by the Transmembrane Protease TMPRSS2","volume":"84","author":"Matsuyama","year":"2010","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1128\/JVI.02062-10","article-title":"A Transmembrane Serine Protease Is Linked to the Severe Acute Respiratory Syndrome Coronavirus Receptor and Activates Virus Entry","volume":"85","author":"Shulla","year":"2011","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1158\/2159-8290.CD-20-0451","article-title":"TMPRSS2 and COVID-19: Serendipity or Opportunity for Intervention?","volume":"10","author":"Stopsack","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.cell.2020.04.035","article-title":"SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues","volume":"181","author":"Ziegler","year":"2020","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/41131","article-title":"A human homologue of the Drosophila toll protein signals activation of adaptive immunity","volume":"388","author":"Medzhitov","year":"1997","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.immuni.2020.05.004","article-title":"Respiratory Virus Infections: Understanding COVID-19","volume":"52","author":"Subbarao","year":"2020","journal-title":"Immunity"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.cell.2008.02.043","article-title":"Identification of Oxidative Stress and Toll-like Receptor 4 Signaling as a Key Pathway of Acute Lung Injury","volume":"133","author":"Imai","year":"2008","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e20200678","DOI":"10.1084\/jem.20200678","article-title":"The many faces of the anti-COVID immune response","volume":"217","author":"Vardhana","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: A complex web of host defenses","volume":"32","author":"Schneider","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/ng1097","article-title":"Impaired response to interferon-\u03b1\/\u03b2 and lethal viral disease in human STAT1 deficiency","volume":"33","author":"Dupuis","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e79","DOI":"10.1016\/j.ijid.2012.05.191","article-title":"IFITM3 restricts the morbidity and mortality associated with influenza","volume":"16","author":"Everitt","year":"2012","journal-title":"Int. J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1146\/annurev-virology-092818-015756","article-title":"Interferon-Stimulated Genes: What Do They All Do?","volume":"6","author":"Schoggins","year":"2019","journal-title":"Annu. Rev. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107","DOI":"10.20411\/pai.v1i1.125","article-title":"Interferons and HIV Infection: The Good, the Bad, and the Ugly","volume":"1","author":"Utay","year":"2016","journal-title":"Pathog. Immun."},{"key":"ref_19","first-page":"eabc3545","article-title":"Type III interferons disrupt the lung epithelial barrier upon viral recognition","volume":"3545","author":"Broggi","year":"2020","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11515","DOI":"10.1128\/JVI.01703-09","article-title":"Lambda Interferon Is the Predominant Interferon Induced by Influenza A Virus Infection In Vivo","volume":"84","author":"Jewell","year":"2010","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.chom.2016.01.007","article-title":"Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice","volume":"19","author":"Channappanavar","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13334","DOI":"10.1128\/JVI.01689-12","article-title":"Induction of Alternatively Activated Macrophages Enhances Pathogenesis during Severe Acute Respiratory Syndrome Coronavirus Infection","volume":"86","author":"Page","year":"2012","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41586-020-2588-y","article-title":"Longitudinal analyses reveal immunological misfiring in severe COVID-19","volume":"584","author":"Lucas","year":"2020","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/d41586-020-02379-1","article-title":"COVID-19 poses a riddle for the immune system","volume":"584","author":"Perlman","year":"2020","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1101\/gad.2.4.383","article-title":"Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control","volume":"2","author":"Levy","year":"1988","journal-title":"Genes Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1073\/pnas.92.9.3829","article-title":"Tyrosine-phosphorylated Stat1 and Stat2 plus a 48-kDa protein all contact DNA in forming interferon-stimulated-gene factor 3","volume":"92","author":"Qureshi","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e23931","DOI":"10.4161\/jkst.23931","article-title":"Transcriptional regulation by STAT1 and STAT2 in the interferon JAK-STAT pathway","volume":"2","author":"Mandhana","year":"2013","journal-title":"Jak-Stat"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1016\/j.peptides.2011.08.009","article-title":"Identifying the regulatory element for human angiotensin-converting enzyme 2 (ACE2) expression in human cardiofibroblasts","volume":"32","author":"Kuan","year":"2011","journal-title":"Peptides"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.3389\/fimmu.2018.01135","article-title":"A positive feedback amplifier circuit that regulates interferon (IFN)-stimulated gene expression and controls type I and type II IFN responses","volume":"9","author":"Michalska","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e00127-20","DOI":"10.1128\/JVI.00127-20","article-title":"Receptor Recognition by the Novel Coronavirus from Wuhan: An Analysis Based on Decade-Long Structural Studies of SARS Coronavirus","volume":"94","author":"Wan","year":"2020","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.chom.2020.04.017","article-title":"Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients","volume":"27","author":"Zhou","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e20201241","DOI":"10.1084\/jem.20201241","article-title":"Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling","volume":"217","author":"Israelow","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e0240647","DOI":"10.1371\/journal.pone.0240647","article-title":"Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2","volume":"15","author":"Barker","year":"2020","journal-title":"PLoS ONE"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1093\/nar\/gkg108","article-title":"TRANSFAC\u00ae: Transcriptional regulation, from patterns to profiles","volume":"31","author":"Matys","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1093\/bioinformatics\/btl633","article-title":"Enrichment or depletion of a GO category within a class of genes: Which test?","volume":"23","author":"Rivals","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/10343","article-title":"Systematic determination of genetic network architecture","volume":"22","author":"Tavazoie","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7028","DOI":"10.1093\/nar\/gku415","article-title":"Bookmarking promoters in mitotic chromatin: Poly(ADP-ribose)polymerase-1 as an epigenetic mark","volume":"42","author":"Lodhi","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s40610-016-0029-3","article-title":"Mitotic bookmarking: Maintaining post-mitotic reprogramming of transcription reactivation","volume":"2","author":"Lodhi","year":"2016","journal-title":"Curr. Mol. Biol. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1101\/gad.206458.112","article-title":"Bookmarking by specific and nonspecific binding of FoxA1 pioneer factor to mitotic chromosomes","volume":"27","author":"Caravaca","year":"2013","journal-title":"Genes Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.cell.2012.06.038","article-title":"Tissue-specific mitotic bookmarking by hematopoietic transcription factor GATA1","volume":"150","author":"Kadauke","year":"2012","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1158\/1541-7786.MCR-13-0672","article-title":"Transcriptional roles of PARP1 in cancer","volume":"12","author":"Schiewer","year":"2014","journal-title":"Mol. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1101\/gad.334425.119","article-title":"The impact of PARPs and ADP-ribosylation on inflammation and host-pathogen interactions","volume":"34","author":"Fehr","year":"2020","journal-title":"Genes Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3931","DOI":"10.1038\/s41467-021-24225-2","article-title":"Nuclear ADP-ribosylation drives IFN\u03b3-dependent STAT1\u03b1 enhancer formation in macro phages","volume":"12","author":"Gupte","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6205","DOI":"10.1073\/pnas.1019644108","article-title":"Drosophila histone H2A variant (H2Av) controls poly(ADP-ribose) polymerase 1 (PARP1) activation","volume":"108","author":"Kotova","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0092-8674(02)00822-X","article-title":"Modifying gene expression programs by altering core promoter chromatin architecture","volume":"110","author":"Lomvardas","year":"2002","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.molcel.2014.01.005","article-title":"Kinase-mediated changes in nucleosome conformation trigger chromatin decondensation via poly(ADP-ribosyl)ation","volume":"53","author":"Thomas","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.molcel.2010.08.014","article-title":"PARP-1 Regulates Chromatin Structure and Transcription through a KDM5B-Dependent Pathway","volume":"39","author":"Krishnakumar","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1101\/gad.1003902","article-title":"The Drosophila heterochromatic gene encoding poly(ADP-ribose) polymerase (PARP) is required to modulate chromatin structure during development","volume":"16","author":"Tulin","year":"2002","journal-title":"Genes Dev."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Boamah, E.K., Kotova, E., Garabedian, M., Jarnik, M., and Tulin, A.V. (2012). Poly(ADP-ribose) polymerase 1 (PARP-1) regulates ribosomal biogenesis in Drosophila nucleoli. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002442"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1242\/jcs.01606","article-title":"PARP-1 and PARP-2 interact with nucleophosmin\/B23 and accumulate in transcriptionally active nucleoli","volume":"118","author":"Meder","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.gde.2010.06.001","article-title":"The roles of PARP1 in gene control and cell differentiation","volume":"20","author":"Ji","year":"2010","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1126\/science.1078764","article-title":"Chromatin loosening by poly(ADP)-ribose polymerase (PARP) at Drosophila puff loci","volume":"299","author":"Tulin","year":"2003","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.molcel.2011.11.015","article-title":"Activator-induced spread of poly(ADP-Ribose) polymerase promotes nucleosome Loss at Hsp70","volume":"45","author":"Petesch","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.cell.2004.11.002","article-title":"NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1","volume":"119","author":"Kim","year":"2004","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"11341","DOI":"10.1074\/jbc.275.15.11341","article-title":"Nitrosative capacity of macrophages is dependent on nitric-oxide synthase induction signals","volume":"275","author":"Espey","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1189\/jlb.1010550","article-title":"Nitric oxide and redox mechanisms in the immune response","volume":"89","author":"Wink","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.freeradbiomed.2006.01.037","article-title":"Role of epithelial nitric oxide in airway viral infection","volume":"41","author":"Xu","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1161\/CIRCRESAHA.117.311401","article-title":"Reactive oxygen species in metabolic and inflammatory signaling","volume":"122","author":"Forrester","year":"2018","journal-title":"Circ. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"22635","DOI":"10.1074\/jbc.273.35.22635","article-title":"Inducible nitric-oxide synthase generates superoxide from the reductase domain","volume":"273","author":"Xia","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9573","DOI":"10.1074\/jbc.274.14.9573","article-title":"Mechanism of superoxide generation by neuronal nitric-oxide synthase","volume":"274","author":"Pou","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.phrs.2016.09.010","article-title":"Novel celecoxib analogues inhibit glial production of prostaglandin E2, nitric oxide, and oxygen radicals reverting the neuroinflammatory responses induced by misfolded prion protein fragment 90\u2013231 or lipopolysaccharide","volume":"113","author":"Villa","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1580967","DOI":"10.1155\/2016\/1580967","article-title":"Reactive Oxygen Species Regulate T Cell Immune Response in the Tumor Microenvironment","volume":"2016","author":"Chen","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4880","DOI":"10.4049\/jimmunol.153.11.4880","article-title":"Longitudinal exposure of human T lymphocytes to weak oxidative stress suppresses transmembrane and nuclear signal transduction","volume":"153","author":"Flescher","year":"1994","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1002\/jlb.63.6.775","article-title":"CD28-mediated activation in CD45RA+ and CD45RO+ T cells: Enhanced levels of reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells","volume":"63","author":"Lahdenpohja","year":"1998","journal-title":"J. Leukoc. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Dayal, D., and Gupta, S. (2020). Connecting BCG Vaccination and COVID-19: Additional Data. medRxiv.","DOI":"10.1101\/2020.04.07.20053272"},{"key":"ref_66","first-page":"185","article-title":"The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly","volume":"43","author":"Datau","year":"2011","journal-title":"Acta Med. Indones."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3143\/geriatrics.42.34","article-title":"Prevention of elderly pneumonia by pneumococcal, influenza and BCG vaccinations","volume":"42","author":"Ohrui","year":"2005","journal-title":"Jpn. J. Geriatr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/trstmh\/tru197","article-title":"BCG-associated heterologous immunity, a historical perspective: Intervention studies in animal models of infectious diseases","volume":"109","author":"Freyne","year":"2014","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/infdis\/136.2.171","article-title":"Nonspecific protection of mice against influenza virus infection by local or systemic immunization with Bacille Calmette-Gu\u00e9rin","volume":"136","author":"Spencer","year":"1977","journal-title":"J. Infect. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/j.cmi.2019.04.020","article-title":"Non-specific effects of BCG vaccine on viral infections","volume":"25","author":"Moorlag","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4913","DOI":"10.1007\/s13277-015-3602-0","article-title":"Gene polymorphisms in the folate metabolism and their association with MTX-related adverse events in the treatment of ALL","volume":"36","author":"Chen","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"30","DOI":"10.5301\/tj.5000207","article-title":"On and off metronomic oral vinorelbine in elderly women with advanced breast cancer","volume":"101","author":"Salerno","year":"2015","journal-title":"Tumori"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"110635","DOI":"10.18632\/oncotarget.22372","article-title":"Single nucleotide polymorphisms and cancer susceptibility","volume":"8","author":"Deng","year":"2017","journal-title":"Oncotarget"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/ng.3847","article-title":"Contrasting evolutionary genome dynamics between domesticated and wild yeasts","volume":"49","author":"Yue","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1128\/MCB.19.5.3485","article-title":"Transcriptional Cross Talk between NF-\u03baB and p53","volume":"19","author":"Webster","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"7432","DOI":"10.1128\/MCB.25.17.7432-7440.2005","article-title":"Role of Stat3 in Regulating p53 Expression and Function","volume":"25","author":"Niu","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1159\/000154228","article-title":"Is p53 polymorphism maintained by natural selection?","volume":"44","author":"Beckman","year":"1994","journal-title":"Hum. Hered."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/sj.cdd.4401907","article-title":"Polymorphic variants in the p53 pathway","volume":"13","author":"Murphy","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nrc2584","article-title":"p53 polymorphisms: Cancer implications","volume":"9","author":"Whibley","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_80","first-page":"961","article-title":"V Primary structure polymorphism at amino acid residue 72 of human p53","volume":"7","author":"Matlashewski","year":"1987","journal-title":"Mol. Cell. Biol."},{"key":"ref_81","first-page":"117","article-title":"The p53 Codon 72 Polymorphism Modifies the Cellular Response to Inflammatory Challenge in the Liver","volume":"2","author":"Leu","year":"2013","journal-title":"J. Liver"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1096\/fj.09-146001","article-title":"Differential levels of transcription of p53-regulated genes by the arginine\/proline polymorphism: p53 with arginine at codon 72 favors apoptosis","volume":"24","author":"Jeong","year":"2010","journal-title":"FASEB J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1084\/jem.20062476","article-title":"Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population","volume":"204","author":"Bojesen","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.exger.2004.10.001","article-title":"Variation in the human TP53 gene affects old age survival and cancer mortality","volume":"40","author":"Mooijaart","year":"2005","journal-title":"Exp. Gerontol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.4161\/cc.10.9.15344","article-title":"Tissue-specific apoptotic effects of the p53 codon 72 polymorphism in a mouse model","volume":"10","author":"Azzam","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1128\/MCB.01136-10","article-title":"The Codon 72 Polymorphism of p53 Regulates Interaction with NF- B and Transactivation of Genes Involved in Immunity and Inflammation","volume":"31","author":"Frank","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1080\/15384047.2017.1323595","article-title":"The codon 72 polymorphism of p53 influences cell fate following nutrient deprivation","volume":"18","author":"Kung","year":"2017","journal-title":"Cancer Biol. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1016\/j.celrep.2016.02.037","article-title":"The P72R Polymorphism of p53 Predisposes to Obesity and Metabolic Dysfunction","volume":"14","author":"Kung","year":"2016","journal-title":"Cell Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e34701","DOI":"10.7554\/eLife.34701","article-title":"A polymorphism in the tumor suppressor p53 affects aging and longevity in mouse models","volume":"7","author":"Zhao","year":"2018","journal-title":"eLife"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4161\/cc.7.2.5249","article-title":"The common germline Arg72Pro polymorphism of p53 and increased longevity in humans","volume":"7","author":"Bojesen","year":"2008","journal-title":"Cell Cycle"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1158\/1541-7786.MCR-18-1292","article-title":"The Codon 72 TP53Polymorphism Contributes to TSC Tumorigenesis through the Notch-Nodal Axis","volume":"17","author":"Cho","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Schuck-Paim, C., Viboud, C., Simonsen, L., Miller, M.A., Moura, F.E.A., Fernandes, R.M., Carvalho, M.L., and Alonso, W.J. (2012). Were equatorial regions less affected by the 2009 influenza pandemic? The Brazilian experience. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041918"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1177\/1087057116656314","article-title":"Identification of novel inhibitors of the type i interferon induction pathway using cell-based high-throughput screening","volume":"21","author":"Gage","year":"2016","journal-title":"J. Biomol. Screen."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: Update on toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s12026-012-8270-1","article-title":"TLR7 and TLR9 in SLE: When sensing self goes wrong","volume":"53","author":"Celhar","year":"2012","journal-title":"Immunol. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.4110\/in.2018.18.e27","article-title":"Origin and List of Damps","volume":"18","author":"Roh","year":"2018","journal-title":"Immune Netw."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.immuni.2010.03.012","article-title":"Intracellular Toll-like Receptors","volume":"32","author":"Blasius","year":"2010","journal-title":"Immunity"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.molmed.2005.07.006","article-title":"Interferon gene regulation: Not all roads lead to Tolls","volume":"11","author":"Jefferies","year":"2005","journal-title":"Trends Mol. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.molimm.2004.11.007","article-title":"The role of Toll-like receptors in the host response to viruses","volume":"42","author":"Bowie","year":"2005","journal-title":"Mol. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1365-2567.2005.02125.x","article-title":"Identification and characterization of a functional, alternatively spliced Toll-like receptor 7 (TLR7) and genomic disruption of TLR8 in chickens","volume":"114","author":"Philbin","year":"2005","journal-title":"Immunology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.4049\/jimmunol.174.3.1259","article-title":"Synthetic TLR Agonists Reveal Functional Differences between Human TLR7 and TLR8","volume":"174","author":"Gorden","year":"2005","journal-title":"J. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/ni.1733","article-title":"Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells","volume":"10","author":"Mancuso","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1084\/jem.20131044","article-title":"RNA recognition by human TLR8 can lead to autoimmune inflammation","volume":"210","author":"Guiducci","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/ni1118","article-title":"Interferon-\u03b1 induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6","volume":"5","author":"Kawai","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.chom.2009.12.003","article-title":"Immunogenicity of Whole-Parasite Vaccines against Plasmodium falciparum Involves Malarial Hemozoin and Host TLR9","volume":"7","author":"Coban","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/35099560","article-title":"Recognition of double-stranded RNA and activation of NF-kappaB by Toll","volume":"413","author":"Alexopoulou","year":"2001","journal-title":"Nature"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.cell.2020.02.041","article-title":"Toll-like Receptors and the Control of Immunity","volume":"180","author":"Fitzgerald","year":"2020","journal-title":"Cell"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s42269-019-0227-2","article-title":"Toll-like receptors activation, signaling, and targeting: An overview","volume":"43","author":"Sibaii","year":"2019","journal-title":"Bull. Natl. Res. Cent."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1111\/j.1463-1326.2011.01402.x","article-title":"JSH-23 targets nuclear factor-kappa B and reverses various deficits in experimental diabetic neuropathy: Effect on neuroinflammation and antioxidant defence","volume":"13","author":"Kumar","year":"2011","journal-title":"Diabetes Obes. Metab."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/nri3713","article-title":"Assembly and localization of Toll-like receptor signalling complexes","volume":"14","author":"Gay","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.bbadis.2014.04.030","article-title":"Interferon regulatory factors: At the crossroads of immunity, metabolism, and disease","volume":"1852","author":"Zhao","year":"2015","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_112","first-page":"2563","article-title":"Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease","volume":"1843","author":"Turner","year":"2014","journal-title":"BBA Mol. Cell Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/ni875","article-title":"IFN-\u03bbs mediate antiviral protection through a distinct class II cytokine receptor complex","volume":"4","author":"Kotenko","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/366129a0","article-title":"The protein tyrosine kinase JAK1 complements defects in interferon-alpha\/beta and -gamma signal transduction","volume":"366","author":"Muller","year":"1993","journal-title":"Nature"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1042\/bj20021935","article-title":"Cloning of a new type II cytokine receptor activating signal transducer and activator of transcription (STAT)1, STAT2 and STAT3","volume":"370","author":"Dumoutier","year":"2003","journal-title":"Biochem. J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nri3581","article-title":"Donlin1 Regulation of type I interferon responses Lionel","volume":"14","author":"Ivashkiv","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.immuni.2012.03.013","article-title":"The JAK-STAT Pathway at Twenty","volume":"36","author":"Stark","year":"2012","journal-title":"Immunity"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.0105-2896.2004.00204.x","article-title":"Interferons, interferon-like cytokines, and their receptors","volume":"202","author":"Pestka","year":"2004","journal-title":"Immunol. Rev."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1001\/jama.2020.8189","article-title":"SARS-CoV-2 Rates in BCG-Vaccinated and Unvaccinated Young Adults","volume":"323","author":"Hamiel","year":"2020","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1136\/jcp.2006.038893","article-title":"Children\u2019s vaccines do not induce cross reactivity against SARS-CoV","volume":"60","author":"Yu","year":"2007","journal-title":"J. Clin. Pathol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.cell.2020.04.042","article-title":"Trained Immunity: A Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection","volume":"181","author":"Netea","year":"2020","journal-title":"Cell"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.bcp.2019.03.021","article-title":"Non-NAD-like PARP-1 inhibitors in prostate cancer treatment","volume":"167","author":"Karpova","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ebiom.2016.10.001","article-title":"Non-NAD-Like poly(ADP-Ribose) Polymerase-1 Inhibitors effectively Eliminate Cancer in vivo","volume":"13","author":"Thomas","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e1125","DOI":"10.1016\/S2214-109X(20)30318-1","article-title":"Correspondence Dexamethasone for COVID-19: Data needed from randomised clinical trials in Africa","volume":"8","author":"Brotherton","year":"2020","journal-title":"Lancet Glob. Health"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e000261","DOI":"10.1136\/lupus-2018-000261","article-title":"Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus","volume":"5","author":"Riggs","year":"2018","journal-title":"Lupus Sci. Med."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Ho, J., Pelzel, C., Begitt, A., Mee, M., Elsheikha, H.M., Scott, D.J., and Vinkemeier, U. (2016). STAT2 Is a Pervasive Cytokine Regulator due to Its Inhibition of STAT1 in Multiple Signaling Pathways. PLoS Biol., 14.","DOI":"10.1371\/journal.pbio.2000117"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"8594","DOI":"10.1021\/acs.jmedchem.8b01397","article-title":"A Dual Inhibition, a Better Solution: Development of a JAK1\/TYK2 inhibitor","volume":"61","author":"Menet","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"8597","DOI":"10.1021\/acs.jmedchem.8b00917","article-title":"Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of ((S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841)","volume":"61","author":"Fensome","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1101\/sqb.2013.78.020321","article-title":"The IRF family transcription factors at the interface of innate and adaptive immune responses","volume":"78","author":"Ikushima","year":"2013","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.immuni.2006.08.009","article-title":"Type I Inteferon Gene Induction by the Interferon Regulatory Factor Family of Transcription Factors","volume":"25","author":"Honda","year":"2006","journal-title":"Immunity"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nri1900","article-title":"IRFs: Master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors","volume":"6","author":"Honda","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"15989","DOI":"10.1073\/pnas.0508327102","article-title":"Negative regulation of Toll-like-receptor signaling by IRF-4","volume":"102","author":"Negishi","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"48788","DOI":"10.18632\/oncotarget.9195","article-title":"Targeted inhibition of STATs and IRFs as a potential treatment strategy in cardiovascular disease","volume":"7","author":"Szelag","year":"2016","journal-title":"Oncotarget"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.3389\/fimmu.2019.01176","article-title":"Direct inhibition of IRF-dependent transcriptional regulatory mechanisms associated with disease","volume":"10","author":"Antonczyk","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nri.2017.142","article-title":"NF-B, inflammation, immunity and cancer: Coming of age","volume":"18","author":"Taniguchi","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1158\/0008-5472.CAN-13-1070","article-title":"p53 and NF-kappaB Co-Regulate Pro-Inflammatory Gene Responses in Human Macrophages","volume":"74","author":"Lowe","year":"2014","journal-title":"Cancer Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1126\/science.8080500","article-title":"Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity","volume":"263","author":"Zhang","year":"1994","journal-title":"Science"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"350","DOI":"10.4049\/jimmunol.156.1.350","article-title":"Peroxynitrite-mediated DNA strand breakage activates poly-adenosine diphosphate ribosyl synthetase and causes cellular energy depletion in macrophages stimulated with bacterial lipopolysaccharide","volume":"156","author":"Zingarelli","year":"1996","journal-title":"J. Immunol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1006\/bbrc.1998.8113","article-title":"Inhibitors of ADP-Ribosylation impair inducible nitric oxide synthase gene transcription through inhibition of NF kappa B activation","volume":"243","author":"Sanceau","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"6887","DOI":"10.1038\/sj.onc.1209982","article-title":"Inhibitors of NF-\u03baB signaling: 785 and counting","volume":"25","author":"Gilmore","year":"2006","journal-title":"Oncogene"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1177\/1087057115617456","article-title":"Modulation of NF-\u03baB Signaling as a Therapeutic Target in Autoimmunity","volume":"21","author":"Herrington","year":"2016","journal-title":"J. Biomol. Screen."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0065-3527(05)65005-1","article-title":"Alteration and Analyses of Viral Entry with Library-Derived Peptides","volume":"65","author":"Bupp","year":"2005","journal-title":"Adv. Virus Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nrmicro2147","article-title":"Coronaviruses post-SARS: Update on replication and pathogenesis","volume":"7","author":"Perlman","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_145","doi-asserted-by":"crossref","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":"ref_146","doi-asserted-by":"crossref","first-page":"11876","DOI":"10.1073\/pnas.0505577102","article-title":"Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry","volume":"102","author":"Simmons","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/S0092-8674(03)00976-0","article-title":"The Secret Life of ACE2 as a Receptor for the SARS Virus","volume":"115","author":"Dimitrov","year":"2003","journal-title":"Cell"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"320","DOI":"10.14740\/jocmr4161","article-title":"Simultaneous Treatment of COVID-19 With Serine Protease Inhibitor Camostat and\/or Cathepsin L Inhibitor?","volume":"12","author":"Bittmann","year":"2020","journal-title":"J. Clin. Med. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biochi.2017.07.016","article-title":"TMPRSS2: A potential target for treatment of influenza virus and coronavirus infections","volume":"142","author":"Shen","year":"2017","journal-title":"Biochimie"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1158\/2159-8290.CD-13-1010","article-title":"The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis","volume":"4","author":"Lucas","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Bestle, D., Heindl, M.R., Limburg, H., Van Lam van, T., Pilgram, O., Moulton, H., Stein, D.A., Hardes, K., Eickmann, M., and Dolnik, O. (2020). TMPRSS2 and furin are both essential for proteolytic activation and spread of SARS-CoV-2 in human airway epithelial cells and provide promising drug targets. bioRxiv.","DOI":"10.1101\/2020.04.15.042085"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"6532","DOI":"10.1128\/AAC.01043-16","article-title":"Respiratory Syndrome Coronavirus S Protein-Mediated Membrane","volume":"60","author":"Yamamoto","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.cmet.2018.03.004","article-title":"RNA-Targeted Therapeutics","volume":"27","author":"Crooke","year":"2018","journal-title":"Cell Metab."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Barrey, E., Burzio, V., Dhorne-pollet, S., and Delmas, B. (2020). Think Different with RNA Therapy: Can Antisense Oligonucleotides Be Used to Inhibit Replication and Transcription of SARS-Cov-2 ?. Prepints, 2020040412.","DOI":"10.20944\/preprints202004.0412.v1"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/978-0-387-33012-9_103","article-title":"Inhibition and escape of SARS-CoV treated with antisense morpholino oligomers","volume":"581","author":"Neuman","year":"2006","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_156","first-page":"38","article-title":"Antisense Technology","volume":"9","author":"Gupta","year":"2011","journal-title":"Int. J. Pharm. Sci. Rev."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Mohammed, K.-S., and Scanlon, K.J. (2005). Antisense and Ribozyme Therapy. The Cancer Handbook, John Wiley & Sons.","DOI":"10.1002\/0470025077.chap91"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"10406","DOI":"10.1073\/pnas.0704178104","article-title":"Riboswitching on RNA virus replication","volume":"104","author":"Wang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.jmb.2015.12.022","article-title":"Functionalization of an Antisense Small RNA","volume":"428","author":"Rodrigo","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.addr.2018.12.013","article-title":"Phage-based vaccines","volume":"145","author":"Bao","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_161","first-page":"3237","article-title":"Bacteriophages Could Be a Potential Game Changer in the Trajectory of Coronavirus Disease (COVID-19) Bacteriophages Used for Accelerated Therapeutic Antibody Production","volume":"1","author":"Wojewodzic","year":"2020","journal-title":"Ther. Appl. Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.cell.2020.04.020","article-title":"Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza","volume":"181","author":"Abbott","year":"2020","journal-title":"Cell"},{"key":"ref_163","first-page":"7504","article-title":"DNA damage response and immune defense: Links and mechanisms","volume":"21","author":"Nakad","year":"2016","journal-title":"Front. Genet."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"e24655","DOI":"10.7554\/eLife.24655","article-title":"A type I IFN-dependent DNA damage response regulates the genetic program and inflammasome activation in macrophages","volume":"6","author":"Morales","year":"2017","journal-title":"eLife"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"(2021). Dexamethasone in Hospitalized Patients with Covid-19. N. Engl. J. Med., 384, 693\u2013704.","DOI":"10.1056\/NEJMoa2021436"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"26","DOI":"10.5414\/ALX02215E","article-title":"Severe allergic reactions to the COVID-19 vaccine\u2014Statement and practical consequences","volume":"5","author":"Klimek","year":"2021","journal-title":"Allergol. Sel."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0140-6736(20)32661-1","article-title":"Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK","volume":"397","author":"Voysey","year":"2021","journal-title":"Lancet"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1001\/jama.2020.27124","article-title":"Genetic Variants of SARS-CoV-2\u2014What Do They Mean?","volume":"325","author":"Lauring","year":"2021","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1001\/jama.2021.2294","article-title":"SARS-CoV-2 Variants of Concern in the United States\u2014Challenges and Opportunities","volume":"325","author":"Walensky","year":"2021","journal-title":"JAMA"},{"key":"ref_171","unstructured":"Zimmer, K. (2021, August 09). A Guide to Emerging SARS-CoV-2 Variants|The Scientist Magazine\u00ae, The Scientist, Available online: https:\/\/www.the-scientist.com\/news-opinion\/a-guide-to-emerging-sars-cov-2-variants-68387."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1038\/s41564-021-00932-w","article-title":"SARS-CoV-2 Variants of Interest and Concern naming scheme conducive for global discourse","volume":"6","author":"Konings","year":"2021","journal-title":"Nat. Microbiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8660\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:44:46Z","timestamp":1760165086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,12]]},"references-count":172,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22168660"],"URL":"https:\/\/doi.org\/10.3390\/ijms22168660","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,12]]}}}