Tetraciclinas: ¿Antibióticos de uso potencial en la COVID-19?
Tetracyclines: antibiotics of potential use in Covid-19?
Palabras clave:
COVID-19, SARS-CoV-2, tetraciclina, terapia antiviral
Resumen
Las tetraciclinas se han utilizado para tratar muchas infecciones bacterianas. El uso de estos antibióticos para el tratamiento de enfermedades virales se remonta a las décadas de 1960 y 1970. Estudios posteriores han demostrado la eficacia de las tetraciclinas como fármaco antiviral en modelos experimentales y estudios in vitro. Las tetraciclinas pueden actuar sobre las infecciones virales por diversos mecanismos, en los que se incluyen: capacidad de inhibir las metaloproteinasas, efectos antinflamatorios, inhibición de la vía NF-kB, efecto anti-apoptótico y antioxidante, inhibición de síntesis de proteínas, inhibición de proteínas estructurales, de proteasas y ARN virales, entre otras propiedades. De esta manera, las tetraciclinas representan un potencial fármaco contra la infección por el SARS-CoV-2. A pesar del potencial de las tetraciclinas como fármacos antivirales, se requieren más estudios clínicos. Es importante desarrollar tratamientos antivirales para el COVID-19, que puedan administrarse en una fase temprana de la infección, con el fin de evitar el daño orgánico causado por el virus y permitir que el paciente produzca una fuerte respuesta inmunitaria. Esta revisión se centra en los datos clínicos y experimentales que apoyan el uso de tetraciclina en el tratamiento de las infecciones virales y destaca un enfoque importante para frenar la progresión de la enfermedad durante la infección viral. El tratamiento con tetraciclina podría representar una estrategia para eliminar la infección o inhibir la progresión de la COVID-19.
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Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei J, Wu X, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China. Lancet 2020;395: 497-506.
Rodríguez-Morales AJ, MacGregor K, Kanagarajah S, Patel D, Schlagenhauf P. Going globaltravel and the 2019 novel coronavirus. Travel Med Infect Dis 2020;33:1-5.
Goulden V. Guidelines for the management of acne vulgaris in adolescents. Paediatr Drugs 2003; 5:301–313.
Smilack JD. The tetracyclines. Mayo Clin Proc 1999; 74:727–729.
Macdonald H, Kelly RG, Allen ES, Noble JF, Kanegis LA. Pharmacokinetic studies on minocycline in man. Clin Pharmacol Ther 1973; 14:852–861.
Carney S, Butcher RA, Dawborn JK, Pattison G. Minocycline excretion and distribution in relation to renal function in man. Clin Exp Pharmacol Physiol 1974;1:299–308.
Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol 2007; 6:1045–1053.
Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A. Minocycline treatment in acute stroke: an openlabel, evaluator blinded study. Neurology 2007; 69:1404–1410.
Thomas M, Le WD. Minocycline: neuroprotective mechanisms in Parkinson’s disease. Curr Pharm Des 2004; 10:679–686.
Zabad RK, Metz LM, Todoruk TR, Zhang Y, Mitchell JR, Yeung M. The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study. Mult Scler 2007;13:517–526.
Michalopoulos A. A clinical and laboratory study of doxycycline (‘Vibramycin’): a broad spectrum antibiotic. Curr Med Res Opin 1973; 1:445–455.
Pulverer G. Doxycycline a broad spectrum antibiotic of the tetracycline series. Med Klin 1969; 64:1033–1037.
Krakauer T, Buckley M. Doxycycline is anti-inflammatory and inhibits staphylococcal exotoxin-induced cytokines and chemokines. Antimicrob Agents Chem 2003; 47:3630–3633.
Cazalis J, Bodet C, Gagnon G. Doxycycline reduces lipopolysaccharide induced inflammatory mediator secretion in macrophage and ex vivo human whole blood models. J Periodontol 2008;79:1762–1768.
Joshi NJ, Miller D. Doxycycline revisited. Arch Intern Med 1997;157:1421–1428.
Negrette A. Encefalitis epidémica. Invest Clin 1960; 1:13–34.
Negrette A, Mosquera J. Epidemia de encefalitis de 1959 en Maracaibo (San Francisco), Estado Zulia, Venezuela. Manifestaciones clínicas y terapéutica antibiótica. Invest Clin 1974; 15:11–44.
Negrette A, Maso-Dominguez J, Rollings CL. Mononucleosis Infecciosa epidémica. Invest Clin 1964; 5:49–53.
Negrette A. Encefalitis equina venezolana. Leucocitos vacuolados. Invest Clin 1968; 26:97–107.
Negrette A. Parálisis facial y tetraciclina. Invest Clin 1968b; 26:5–6.
Negrette A. Tetraciclina y virus pequeños Editorial. Invest Clin 1980; 21:235–238.
Negrette A. Tetraciclina y Sida. Invest Clin 1990; 31:117–119.
Negrette A, Hernandez H. Therapeutic effect of tetracycline in the experimental venezuelan encephalitis. Invest Clin 1974; 15:45–51.
Negrette A, Soto Escalona A, Ryder S. Acción de la tetraciclina sobre la encefalitis venezolana experimental. Comunicacion preliminar. Invest Clin 1970; 36:7–11.
Masters PS. The molecular biology of coronaviruses. Adv Virus Res 2006;66:193-292.
de Groot RJ. Structure, function and evolution of the hemagglutinin esterase proteins of corona and toroviruses. Glycoconj J 2006;23:59-72.
Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong JC, Turner AJ. Angiotensincon verting enzyme 2: SARS-CoV-2 receptor and regulator of the renin angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. Circ Res 2020;126: 1456- 1474.
Jothimani D, Venugopal R, Abedin MF, Kaliamoorthy I, Rela M. COVID-19 and the liver. J Hepatol 2020;73:1231-1240.
Mosquera-Sulbaran J, Adriana Pedreañez, Yenddy Carrero, Diana Callejas. Creactive protein as an effector molecule in the COVID-19 pathogenesis. Rev Med Virol 2021; 1-8, e2221.
Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 2020;367:1444-1448.
Shang J, Ye G, Shi K, Wan Y, Luo C, Aihar H, Geng Q, Auerbach A, Li F. Structural basis of receptor recognition by SARS- CoV-2. Nature 2020;581:221-224.
Millet JK, Whittaker GR. Host cell proteases: critical determinants of coronavirus tropism and pathogenesis. Virus Res 2015; 202:120-134.
Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin converting enzyme2 is a functional receptor for the SARS coronavirus. Nature 2003; 426:450-454.
Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 2020;181:281-292.
Wang H, Yang P, Liu K, Guo F, Zhang Y, Zhang G, Jiang C. SARS coronavirus entry into host cells through a novel clathrin and caveolae independent endocytic pathway. Cell Res 2008; 18:290-301.
Santos RA, Simoes e Silva AC, Maric C, Silva DMR, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SVB, Lopes MT, Bader M, Mendes EP, Soares Lemos V, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T. Angiotensin (1-7) is an endogenous ligand for the G protein coupled receptor Mas. Proc Natl Acad Sci USA 2003;100:8258-8263.
Patel VB, Clarke N, Wang Z, Fan D, Parajuli N, Basu R, Putko B, Kassiri Z, Turner AJ, Oudit GY. Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17: a positive feedback mechanism in the RAS. J Mol Cell Cardiol 2014;66:167-176.
Kim JM, Heo HS, Ha YM, Hyeok Ye BH, Lee EK, Choi YJ, Yu BP, Chung HY. Mechanism of Ang II involvement in activation of NF-κB through phosphorylation of p65 during aging. Age (Dordr) 2012; 34:11-25.
Scott AJ, O’Dea KP, O’Callaghan D, Lynn Williams L, Justina O Dokpesi JO, Louise Tatton L, Jonathan M Handy JM, Philip J Hogg PJ, Masao Takata M. Reactive oxygen species and p38 mitogen activated protein kinase mediate tumor necrosis factor α-converting enzyme (TACE/ADAM-17) activation in primary human monocytes. J Biol Chem 2011;286:35466-35476.
Black RA, Rauch CT, Kozlosky CJ, Peschon J J, Slack J L, Wolfson M F, Castner B J, Stocking K L, Reddy P, Srinivasan S, Nelson N, Boiani N, Schooley K A, Gerhart M, Davis R, Fitzner J N, Johnson R S, Paxton R J, March C J, Cerretti D P. A metalloproteinase disintegrin that releases tumour necrosis factor alpha from cells. Nature 1997;385:729-733.
Moss ML, Jin SL, Milla ME, Burkhart W, Carter H L, Chen W J, Clay W C, Didsbury J R, Hassler D, Hoffman C R, Kost T A, Lambert M H, Leesnitzer M A, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton L K, Schoenen F, Seaton T, Su J L, Becherer J D. Cloning of a disintegrin metalloproteinase that processes precursor tumour necrosis factor alpha. Nature 1997; 385:733-736.
Xu J, Sriramula S, Xia H, Moreno-Walton L, Culicchia F, Domenig O, Poglitsch M, Lazartigues E. Clinical relevance and role of neuronal AT1 receptors in ADAM17 mediated ACE2 shedding in neurogenic hypertension. Circ Res 201.7;121:43-55.
Pedreañez A, Mosquera-Sulbaran J, Muñoz N. SARS-CoV-2 infection represents a high risk for the elderly: analysis of pathogenesis. Arch Virol 2021;166:1565-1574.
Hash JH, Wishnick M, Miller PA. On the mode of action of the tetracycline antibiotics in Staphylococcus aureus. J Biol Chem 1964; 239:2070–2078.
Tritton TR. Ribosome tetracycline interactions. Biochemistry 1977;16:4133-4138.
Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev Am Soc Microbiol 2001;65:232–260.
Semenkov YP, Makarov EM, Makhno VI, Kirillov SV. Kinetic aspects of tetracycline action on the acceptor (A) site of Escherichia coli ribosomes. FEBS Lett 1982; 144:125–129.
Rohde LE, Ducharme A, Arroyo LH, Aikawa M, Sukhova GH, Lopez-Anaya A, McClure KF, Mitchell PG, Libby P, Lee RT. Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice. Circulation 1999; 99:3063–3070.
Peterson JT. Matrix metalloproteinase inhibitor development and the remodeling of drug discovery. Heart Fail Rev 2004; 9:63– 79.
Nagase H, Woessner JF. Matrix metalloproteinases. J Biol Chem 1999; 274:21491–21494.
Griffin MO, Fricovsky E, Ceballos G, Villarreal F. Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol 2010; 299:C539–C548.
Park JL, Lucchesi BR. Mechanisms of myocardial reperfusion injury. Ann Thorac Surg 1999; 68:1905–1912.
Kraus RL, Pasieczny R, Lariosa-Willingham K, Turner MS, Jiang A, Trauger JW. Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radicalscavenging activity. J Neurochem 2005; 94:819–827.
Yrjänheikki J, Keinänen R, Pellikka M, Hökfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA 1998; 95:15769-15774.
Sanchez Mejia RO, Ona VO, Li M, Friedlander RM. Minocycline reduces traumatic brain injury mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery 2001; 48:1393–1399.
Du Y, Ma Z, Lin S, Dodel RC, Gao F, Bales KR, Triarhou LC, Chernet E, Perry KW, Nelson DL, Luecke S, Phebus LA, By master FP, Paul SM. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the M.PTP model of Parkinson’s disease. Proc Natl Acad Sci USA 2001; 98:14669-14674.
Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 200l; 6:797-801.
Wang X, Zhu S, Drozda M, Zhang W, Stavrovskaya IG, Cattaneo E, Ferrante RJ, Kristal BS, Friedlander RM. Minocycline inhibits caspase independent and dependent mitochondrial cell death pathways in models of Huntington’s disease. Proc Natl Acad Sci USA 2003; 100:10483–10487.
Pruzanski W, Greenwald RA, Street IO, Laleberte F, Stefanski E, Vadas P. Inhibition of enzymatic activity of phospholipase A2 by minocycline and doxycycline. Biochem Pharmacol 1992; 44:1165–1170.
Esterly NB, Koransky JS, Furey NL, Trevisan M. Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy. Arch Dermatol 1984; 120:1308–1313.
Gable WL, Tsukuda N. The influence of divalent cations and doxycycline on iodoacetamide inhibitable leukocyte adherence. Res Commun Chem Pathol Pharmacol 1991; 74:131–140.
Thong YH, Ferrante A. Inhibition of mitogen induced human lymphocyte proliferative responses by tetracycline analogues. Clin Exp Immunol 1979; 35:443–446.
Ataie-Kachoie P, Badar S, Morris DL, Pourgholami MH. Signal transduction minocycline targets the NF-kB nexus through suppression of TGF-b1-TAK1-IkB signaling in ovarian cancer. Mol Cancer Res 2013; 11:1279–1291.
Sun J, Shigemi H, Tanaka Y, Yamauchi T, Ueda T, Iwasaki H. Tetracyclines down regulate the production of LPS induced cytokines and chemokines in THP-1 cells via ERK, p38, and nuclear factor-κB signaling pathways. Biochem Biophy Rep 2015; 4:397–404.
Mosquera-Sulbaran J, Hernandez-Fonseca H. Tetracycline and viruses: a possible treatment for COVID-19? Arch Virol 2021;166:1-7.
Lemaitre M, Guetard D, Henin Y, Montagnier L, Zerial A. Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells. Res Virol 1990; 141:5–16.
Zink MC, Uhrlaub J, DeWitt J, Voelker T, Bullock B, Mankowski J. Neuroprotective and anti-human immunodeficiency virus activity of minocycline. JAMA 2005; 293:2003–2011.
Follstaedt SC, Barber SA, Zink MC. Mechanisms of minocycline induced suppression of simian immunodeficiency virus encephalitis: inhibition of apoptosis signal regulating kinase 1. J Neurovirol 2008;14:376–388.
Jenwitheesuk E, Samudrala R. Identification of potential HIV-1 targets of minocycline. Bioinformatics 2007; 23:2797–2799.
Michaelis M, Kleinschmidt MC, Doerr HW, Cinat J. Minocycline inhibits West Nile virus replication and apoptosis in human neuronal cells. J Antimicrob Chemother 2007; 60:981–986.
Quick ED, Seitz S, Clarke P, Tyler KL. Minocycline has anti-inflammatory effects and reduces cytotoxicity in an Ex Vivo spinal cord slice culture model of west Nile virus infection. J Virol 2017; 91:e00569-e1517.
Mishra MK, Basu A. Minocycline neuro protects, reduces microglial activation, inhibits caspase 3 induction, and viral replication following Japanese encephalitis. J Neurochem 2008;105:1582–1595.
Lai YC, Chuang YC, Chang CP, Lin YS, Perng GC, Wu HC, Hsieh SL, Yeh TM. Minocycline suppresses dengue virus replication by down regulation of macrophage migration inhibitory factor induced autophagy. Antiviral Res 2018; 155:28–38.
Irani DN, Prow NA. Neuroprotective interventions targeting detrimental host immune responses protect mice from fatal alphavirus encephalitis. J Neuropathol Exp Neurol 2007; 66:533–544.
Valero N, Mosquera J, Alcocer S, Bonilla E, Salazar J, Álvarez- Mon M. Melatonin, minocycline and ascorbic acid reduce oxidative stress and viral titers and increase survival rate in experimental Venezuelan equine encephalitis. Brain Res 2015; 1622:368–376.
Bawage SS, Tiwari PM, Pillai S, Dennis VA, Singh SR. Antibiotic minocycline prevents respiratory syncytial virus infection. Viruses 2019;11:1–10.
Liao YT, Wang SM, Chen SH. Anti-inflammatory and antiviral effects of minocycline in enterovirus 71 infections. Biomed Pharmacother 2019; 118:109271.
Sharifi A, Amanlou A, Moosavi-Movahedi F, Golestanian S, Amanlou M. Tetracyclines as a potential antiviral therapy against Crimean Congo hemorrhagic fever virus: docking and molecular dynamic studies. Comput Biol Chem 2017;70:1–6.
Takaoka A, Hayakawa S, Yanai H. Integration of interferon alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 2003; 424:516–523.
Turpin E, Luke K, Jone J. Influenza virus infection increases p53 activity: role of p53 in cell death and viral replication. J Virol 2005; 79:8802–8811.
Fujioka S, Schmidt C, Sclabas GM, Li Z, Pelicano H, Peng B, Yao A, Niu J, Zhang W, Evans DB, Abbruzzese JL, Huang P, Chiao PJ. Stabilization of p53 is a novel mechanism for proapoptotic function of NF-κB. J Biol Chem 2004; 279:27549–27559.
Wu ZC, Wang X, Wei JC, Li BB, Shao DH, Li YM, Liu K, Shi YY, Zhou B, Qiu YF, Ma ZY. Antiviral activity of doxycycline against vesicular stomatitis virus in vitro. FEMS Microbiol Lett 2015; 362:fnv195.
Li Y, Wu Z, Liu K, Qi P, Xu J, Wei J, Li B, Shao D, Shi Y, Qiu Y, Ma Z. Doxycycline enhances adsorption and inhibits early stage replication of porcine reproductive and respiratory syndrome virus in vitro. FEMS Microbiol Lett 2017; 364:1–6.
Ng HH, Narasaraju T, Phoon MC, Sim MK, Seet JE, Chow VT. Doxycycline treatment attenuates acute lung injury in mice infected with virulent influenza H3N2 virus: involvement of matrix metalloproteinases. Exp Mol Pathol 2012; 92:287–295.
Rothan HA, Bahrani H, Mohamed Z, Teoh TC, Shankar EM, Rahman NA, Yusof R. A combination of doxycycline and ribavirin alleviated chikungunya infection. PLoS ONE 2015;10:e0126360.
Rothan HA, Buckle MJ, Ammar YA, Mohammadjavad P, Shatrah O, Noorsaadah AR, Rohana Y. Study the antiviral activity of some derivatives of tetracycline and nonsteroid anti-inflammatory drugs towards dengue virus. Trop Biomed 2013; 30:681–690.
Rothan HA, Mohamed Z, Paydar M, Rahman NA, Yusof R. Inhibitory effect of doxy cycline against dengue virus replication in vitro. Arch Virol 2014; 159:711–718.
Yang JM, Chen YF, Tu YY, Yen KR, Yang YL. Combinatorial computational approaches to identify tetracycline derivatives as flavi-virus inhibitors. PLoS ONE 2007; 2:e428.
Speer BS, Shoemaker NB, Salyers AA. Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance. Clin Microbiol Rev 1992; 5(4):387–399.
Zakeri B, Wright GD. Chemical biology of tetracycline antibiotics. Biochem Cell Biol 2008; 86:124–136.
Bharadwaja S, Leea KE, Dwivedib VD, Kanga SG. Computational insights into tetracyclines as inhibitors against SARS- CoV-2 Mpro via combinatorial molecular simulation calculations. Life Sci 2020; 257:118080.
Wang J. Fast identification of possible drug treatment of coronavirus disease-19 (COVID-19) through computational drug repurposing study. J Chem Inf Model 2020; 60:3277-3286.
Bhowmik D, Nandi R, Jagadeesan R, Kumar N, Prakash A, Kumar D. Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches. Infect Genet Evol 2020;84:104451.
Ren Y, Shu T, Wu D, Mu J, Wang C, Huang M, Han Y, Zhang XY, Zhou W, Qiu Y, Zhou X. The ORF3a protein of SARSCoV-2 induces apoptosis in cells. Cell Mol Immunol 2020; 18:1–3.
Ahmad I, Alam M, Saadi R, Mahmud S, Saadi E. Doxycycline and Hydroxychloroquine as treatment for high-risk COVID-19 patients: experience from case series of 54 patients in long-term care facilities. medR- xiv 2020; 05:18.20066902.
Roy SK, Kendrick D, Sadowitz BD, Gatto L, Snyder K, Satalin JM, Golub LM, Nieman G. Jack of all trades: pleiotropy and the application of chemically modified tetracycline-3 in sepsis and the acute respiratory distress syndrome (ARDS). Pharmacol Res 2011;64:580–589.
Alam MM, Mahmud S, Rahman MM, Simpson JA, Aggarwal S, Ahmed Z. Clinical outcomes of early treatment with doxycycline for 89 high-risk COVID-19 patients in long-term care facilities in New York. Cureus 2020;12:e9658.
Bonzano C, Borroni D, Lancia A, Bonzano E. Doxycycline: from ocular rosacea to COVID-19 anosmia. New insight into the coronavirus outbreak. Front Med (Lausanne). 2020; 7:200.
Cakir B. A novel approach to managing COVID-19 patients; results of lopinavir plus doxycycline cohort. Eur J Clin Microbiol Infect Dis 2021; 40:663-664.
Cag Y, Icten S, Isik-Goren B, Baysal NB, Bektas B, Selvi E, Ergen P, Aydin O, Ucisik AC, Yilmaz-Karadag F, Caskurlu H, Akarsu-Ayazoglu T, Kocoglu H, Uzman S, Nural-Pamukcu M, Arslan F, Bas G, Kalcioglu MT, Vahaboglu H. A novel approach to managing COVID-19 patients; results of lopinavir plus doxycycline cohort. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol 2021; 40:407-411.
Yates PA, Newman SA, Oshry LJ, Glassman RH, Leone AM, Reichel E. Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease. Ther Adv Respir Dis 2020;14:1753466620951053.
Chowdhury ATMM, Shahbaz M, Karim MR, Islam J, Guo D, He S. A Randomized trial of ivermectin doxycycline and hydroxychloroquine azithromycin therapy on COVID19 patients. Research Square 2020.
Malek AE, Granwehr BP. Doxycycline as an alternative to azithromycin in elderly patients. Int J Antimicrob Agents 2021;57:106168.
Malek AE, Granwehr BP, Kontoyiannis DP. Doxycycline as a potential partner of COVID-19 therapies. IDCases 2020;21: e00864.
Ohe M, Furuya K, Goudarzi H. Tetracycline plus macrolide: A potential therapeutic regimen for COVID-19? BioScience Trends. 2020; 14:467-468.
Byrne JD, Shakur R, Collins JE, Becker S , Young CC, Boyce H, Traverso G. Prophylaxis with tetracyclines in ARDS: potential therapy for COVID-19-induced ARDS?. medRxiv 2020.
Gironi LC, Damiani G, Zavattaro E, Pacifico A, Santus P, Pigatto PDM, Cremona O, Savoia P. Tetracyclines in COVID-19 patients quarantined at home: literature evidence supporting real world data from a multicenter observational study targeting inflammatory and infectious dermatoses. Dermatol Ther 2020;22: e14694.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395:1054–1062.
Rodríguez-Morales AJ, MacGregor K, Kanagarajah S, Patel D, Schlagenhauf P. Going globaltravel and the 2019 novel coronavirus. Travel Med Infect Dis 2020;33:1-5.
Goulden V. Guidelines for the management of acne vulgaris in adolescents. Paediatr Drugs 2003; 5:301–313.
Smilack JD. The tetracyclines. Mayo Clin Proc 1999; 74:727–729.
Macdonald H, Kelly RG, Allen ES, Noble JF, Kanegis LA. Pharmacokinetic studies on minocycline in man. Clin Pharmacol Ther 1973; 14:852–861.
Carney S, Butcher RA, Dawborn JK, Pattison G. Minocycline excretion and distribution in relation to renal function in man. Clin Exp Pharmacol Physiol 1974;1:299–308.
Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol 2007; 6:1045–1053.
Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A. Minocycline treatment in acute stroke: an openlabel, evaluator blinded study. Neurology 2007; 69:1404–1410.
Thomas M, Le WD. Minocycline: neuroprotective mechanisms in Parkinson’s disease. Curr Pharm Des 2004; 10:679–686.
Zabad RK, Metz LM, Todoruk TR, Zhang Y, Mitchell JR, Yeung M. The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study. Mult Scler 2007;13:517–526.
Michalopoulos A. A clinical and laboratory study of doxycycline (‘Vibramycin’): a broad spectrum antibiotic. Curr Med Res Opin 1973; 1:445–455.
Pulverer G. Doxycycline a broad spectrum antibiotic of the tetracycline series. Med Klin 1969; 64:1033–1037.
Krakauer T, Buckley M. Doxycycline is anti-inflammatory and inhibits staphylococcal exotoxin-induced cytokines and chemokines. Antimicrob Agents Chem 2003; 47:3630–3633.
Cazalis J, Bodet C, Gagnon G. Doxycycline reduces lipopolysaccharide induced inflammatory mediator secretion in macrophage and ex vivo human whole blood models. J Periodontol 2008;79:1762–1768.
Joshi NJ, Miller D. Doxycycline revisited. Arch Intern Med 1997;157:1421–1428.
Negrette A. Encefalitis epidémica. Invest Clin 1960; 1:13–34.
Negrette A, Mosquera J. Epidemia de encefalitis de 1959 en Maracaibo (San Francisco), Estado Zulia, Venezuela. Manifestaciones clínicas y terapéutica antibiótica. Invest Clin 1974; 15:11–44.
Negrette A, Maso-Dominguez J, Rollings CL. Mononucleosis Infecciosa epidémica. Invest Clin 1964; 5:49–53.
Negrette A. Encefalitis equina venezolana. Leucocitos vacuolados. Invest Clin 1968; 26:97–107.
Negrette A. Parálisis facial y tetraciclina. Invest Clin 1968b; 26:5–6.
Negrette A. Tetraciclina y virus pequeños Editorial. Invest Clin 1980; 21:235–238.
Negrette A. Tetraciclina y Sida. Invest Clin 1990; 31:117–119.
Negrette A, Hernandez H. Therapeutic effect of tetracycline in the experimental venezuelan encephalitis. Invest Clin 1974; 15:45–51.
Negrette A, Soto Escalona A, Ryder S. Acción de la tetraciclina sobre la encefalitis venezolana experimental. Comunicacion preliminar. Invest Clin 1970; 36:7–11.
Masters PS. The molecular biology of coronaviruses. Adv Virus Res 2006;66:193-292.
de Groot RJ. Structure, function and evolution of the hemagglutinin esterase proteins of corona and toroviruses. Glycoconj J 2006;23:59-72.
Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong JC, Turner AJ. Angiotensincon verting enzyme 2: SARS-CoV-2 receptor and regulator of the renin angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. Circ Res 2020;126: 1456- 1474.
Jothimani D, Venugopal R, Abedin MF, Kaliamoorthy I, Rela M. COVID-19 and the liver. J Hepatol 2020;73:1231-1240.
Mosquera-Sulbaran J, Adriana Pedreañez, Yenddy Carrero, Diana Callejas. Creactive protein as an effector molecule in the COVID-19 pathogenesis. Rev Med Virol 2021; 1-8, e2221.
Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 2020;367:1444-1448.
Shang J, Ye G, Shi K, Wan Y, Luo C, Aihar H, Geng Q, Auerbach A, Li F. Structural basis of receptor recognition by SARS- CoV-2. Nature 2020;581:221-224.
Millet JK, Whittaker GR. Host cell proteases: critical determinants of coronavirus tropism and pathogenesis. Virus Res 2015; 202:120-134.
Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin converting enzyme2 is a functional receptor for the SARS coronavirus. Nature 2003; 426:450-454.
Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 2020;181:281-292.
Wang H, Yang P, Liu K, Guo F, Zhang Y, Zhang G, Jiang C. SARS coronavirus entry into host cells through a novel clathrin and caveolae independent endocytic pathway. Cell Res 2008; 18:290-301.
Santos RA, Simoes e Silva AC, Maric C, Silva DMR, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SVB, Lopes MT, Bader M, Mendes EP, Soares Lemos V, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T. Angiotensin (1-7) is an endogenous ligand for the G protein coupled receptor Mas. Proc Natl Acad Sci USA 2003;100:8258-8263.
Patel VB, Clarke N, Wang Z, Fan D, Parajuli N, Basu R, Putko B, Kassiri Z, Turner AJ, Oudit GY. Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17: a positive feedback mechanism in the RAS. J Mol Cell Cardiol 2014;66:167-176.
Kim JM, Heo HS, Ha YM, Hyeok Ye BH, Lee EK, Choi YJ, Yu BP, Chung HY. Mechanism of Ang II involvement in activation of NF-κB through phosphorylation of p65 during aging. Age (Dordr) 2012; 34:11-25.
Scott AJ, O’Dea KP, O’Callaghan D, Lynn Williams L, Justina O Dokpesi JO, Louise Tatton L, Jonathan M Handy JM, Philip J Hogg PJ, Masao Takata M. Reactive oxygen species and p38 mitogen activated protein kinase mediate tumor necrosis factor α-converting enzyme (TACE/ADAM-17) activation in primary human monocytes. J Biol Chem 2011;286:35466-35476.
Black RA, Rauch CT, Kozlosky CJ, Peschon J J, Slack J L, Wolfson M F, Castner B J, Stocking K L, Reddy P, Srinivasan S, Nelson N, Boiani N, Schooley K A, Gerhart M, Davis R, Fitzner J N, Johnson R S, Paxton R J, March C J, Cerretti D P. A metalloproteinase disintegrin that releases tumour necrosis factor alpha from cells. Nature 1997;385:729-733.
Moss ML, Jin SL, Milla ME, Burkhart W, Carter H L, Chen W J, Clay W C, Didsbury J R, Hassler D, Hoffman C R, Kost T A, Lambert M H, Leesnitzer M A, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton L K, Schoenen F, Seaton T, Su J L, Becherer J D. Cloning of a disintegrin metalloproteinase that processes precursor tumour necrosis factor alpha. Nature 1997; 385:733-736.
Xu J, Sriramula S, Xia H, Moreno-Walton L, Culicchia F, Domenig O, Poglitsch M, Lazartigues E. Clinical relevance and role of neuronal AT1 receptors in ADAM17 mediated ACE2 shedding in neurogenic hypertension. Circ Res 201.7;121:43-55.
Pedreañez A, Mosquera-Sulbaran J, Muñoz N. SARS-CoV-2 infection represents a high risk for the elderly: analysis of pathogenesis. Arch Virol 2021;166:1565-1574.
Hash JH, Wishnick M, Miller PA. On the mode of action of the tetracycline antibiotics in Staphylococcus aureus. J Biol Chem 1964; 239:2070–2078.
Tritton TR. Ribosome tetracycline interactions. Biochemistry 1977;16:4133-4138.
Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev Am Soc Microbiol 2001;65:232–260.
Semenkov YP, Makarov EM, Makhno VI, Kirillov SV. Kinetic aspects of tetracycline action on the acceptor (A) site of Escherichia coli ribosomes. FEBS Lett 1982; 144:125–129.
Rohde LE, Ducharme A, Arroyo LH, Aikawa M, Sukhova GH, Lopez-Anaya A, McClure KF, Mitchell PG, Libby P, Lee RT. Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice. Circulation 1999; 99:3063–3070.
Peterson JT. Matrix metalloproteinase inhibitor development and the remodeling of drug discovery. Heart Fail Rev 2004; 9:63– 79.
Nagase H, Woessner JF. Matrix metalloproteinases. J Biol Chem 1999; 274:21491–21494.
Griffin MO, Fricovsky E, Ceballos G, Villarreal F. Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol 2010; 299:C539–C548.
Park JL, Lucchesi BR. Mechanisms of myocardial reperfusion injury. Ann Thorac Surg 1999; 68:1905–1912.
Kraus RL, Pasieczny R, Lariosa-Willingham K, Turner MS, Jiang A, Trauger JW. Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radicalscavenging activity. J Neurochem 2005; 94:819–827.
Yrjänheikki J, Keinänen R, Pellikka M, Hökfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA 1998; 95:15769-15774.
Sanchez Mejia RO, Ona VO, Li M, Friedlander RM. Minocycline reduces traumatic brain injury mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery 2001; 48:1393–1399.
Du Y, Ma Z, Lin S, Dodel RC, Gao F, Bales KR, Triarhou LC, Chernet E, Perry KW, Nelson DL, Luecke S, Phebus LA, By master FP, Paul SM. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the M.PTP model of Parkinson’s disease. Proc Natl Acad Sci USA 2001; 98:14669-14674.
Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 200l; 6:797-801.
Wang X, Zhu S, Drozda M, Zhang W, Stavrovskaya IG, Cattaneo E, Ferrante RJ, Kristal BS, Friedlander RM. Minocycline inhibits caspase independent and dependent mitochondrial cell death pathways in models of Huntington’s disease. Proc Natl Acad Sci USA 2003; 100:10483–10487.
Pruzanski W, Greenwald RA, Street IO, Laleberte F, Stefanski E, Vadas P. Inhibition of enzymatic activity of phospholipase A2 by minocycline and doxycycline. Biochem Pharmacol 1992; 44:1165–1170.
Esterly NB, Koransky JS, Furey NL, Trevisan M. Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy. Arch Dermatol 1984; 120:1308–1313.
Gable WL, Tsukuda N. The influence of divalent cations and doxycycline on iodoacetamide inhibitable leukocyte adherence. Res Commun Chem Pathol Pharmacol 1991; 74:131–140.
Thong YH, Ferrante A. Inhibition of mitogen induced human lymphocyte proliferative responses by tetracycline analogues. Clin Exp Immunol 1979; 35:443–446.
Ataie-Kachoie P, Badar S, Morris DL, Pourgholami MH. Signal transduction minocycline targets the NF-kB nexus through suppression of TGF-b1-TAK1-IkB signaling in ovarian cancer. Mol Cancer Res 2013; 11:1279–1291.
Sun J, Shigemi H, Tanaka Y, Yamauchi T, Ueda T, Iwasaki H. Tetracyclines down regulate the production of LPS induced cytokines and chemokines in THP-1 cells via ERK, p38, and nuclear factor-κB signaling pathways. Biochem Biophy Rep 2015; 4:397–404.
Mosquera-Sulbaran J, Hernandez-Fonseca H. Tetracycline and viruses: a possible treatment for COVID-19? Arch Virol 2021;166:1-7.
Lemaitre M, Guetard D, Henin Y, Montagnier L, Zerial A. Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells. Res Virol 1990; 141:5–16.
Zink MC, Uhrlaub J, DeWitt J, Voelker T, Bullock B, Mankowski J. Neuroprotective and anti-human immunodeficiency virus activity of minocycline. JAMA 2005; 293:2003–2011.
Follstaedt SC, Barber SA, Zink MC. Mechanisms of minocycline induced suppression of simian immunodeficiency virus encephalitis: inhibition of apoptosis signal regulating kinase 1. J Neurovirol 2008;14:376–388.
Jenwitheesuk E, Samudrala R. Identification of potential HIV-1 targets of minocycline. Bioinformatics 2007; 23:2797–2799.
Michaelis M, Kleinschmidt MC, Doerr HW, Cinat J. Minocycline inhibits West Nile virus replication and apoptosis in human neuronal cells. J Antimicrob Chemother 2007; 60:981–986.
Quick ED, Seitz S, Clarke P, Tyler KL. Minocycline has anti-inflammatory effects and reduces cytotoxicity in an Ex Vivo spinal cord slice culture model of west Nile virus infection. J Virol 2017; 91:e00569-e1517.
Mishra MK, Basu A. Minocycline neuro protects, reduces microglial activation, inhibits caspase 3 induction, and viral replication following Japanese encephalitis. J Neurochem 2008;105:1582–1595.
Lai YC, Chuang YC, Chang CP, Lin YS, Perng GC, Wu HC, Hsieh SL, Yeh TM. Minocycline suppresses dengue virus replication by down regulation of macrophage migration inhibitory factor induced autophagy. Antiviral Res 2018; 155:28–38.
Irani DN, Prow NA. Neuroprotective interventions targeting detrimental host immune responses protect mice from fatal alphavirus encephalitis. J Neuropathol Exp Neurol 2007; 66:533–544.
Valero N, Mosquera J, Alcocer S, Bonilla E, Salazar J, Álvarez- Mon M. Melatonin, minocycline and ascorbic acid reduce oxidative stress and viral titers and increase survival rate in experimental Venezuelan equine encephalitis. Brain Res 2015; 1622:368–376.
Bawage SS, Tiwari PM, Pillai S, Dennis VA, Singh SR. Antibiotic minocycline prevents respiratory syncytial virus infection. Viruses 2019;11:1–10.
Liao YT, Wang SM, Chen SH. Anti-inflammatory and antiviral effects of minocycline in enterovirus 71 infections. Biomed Pharmacother 2019; 118:109271.
Sharifi A, Amanlou A, Moosavi-Movahedi F, Golestanian S, Amanlou M. Tetracyclines as a potential antiviral therapy against Crimean Congo hemorrhagic fever virus: docking and molecular dynamic studies. Comput Biol Chem 2017;70:1–6.
Takaoka A, Hayakawa S, Yanai H. Integration of interferon alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 2003; 424:516–523.
Turpin E, Luke K, Jone J. Influenza virus infection increases p53 activity: role of p53 in cell death and viral replication. J Virol 2005; 79:8802–8811.
Fujioka S, Schmidt C, Sclabas GM, Li Z, Pelicano H, Peng B, Yao A, Niu J, Zhang W, Evans DB, Abbruzzese JL, Huang P, Chiao PJ. Stabilization of p53 is a novel mechanism for proapoptotic function of NF-κB. J Biol Chem 2004; 279:27549–27559.
Wu ZC, Wang X, Wei JC, Li BB, Shao DH, Li YM, Liu K, Shi YY, Zhou B, Qiu YF, Ma ZY. Antiviral activity of doxycycline against vesicular stomatitis virus in vitro. FEMS Microbiol Lett 2015; 362:fnv195.
Li Y, Wu Z, Liu K, Qi P, Xu J, Wei J, Li B, Shao D, Shi Y, Qiu Y, Ma Z. Doxycycline enhances adsorption and inhibits early stage replication of porcine reproductive and respiratory syndrome virus in vitro. FEMS Microbiol Lett 2017; 364:1–6.
Ng HH, Narasaraju T, Phoon MC, Sim MK, Seet JE, Chow VT. Doxycycline treatment attenuates acute lung injury in mice infected with virulent influenza H3N2 virus: involvement of matrix metalloproteinases. Exp Mol Pathol 2012; 92:287–295.
Rothan HA, Bahrani H, Mohamed Z, Teoh TC, Shankar EM, Rahman NA, Yusof R. A combination of doxycycline and ribavirin alleviated chikungunya infection. PLoS ONE 2015;10:e0126360.
Rothan HA, Buckle MJ, Ammar YA, Mohammadjavad P, Shatrah O, Noorsaadah AR, Rohana Y. Study the antiviral activity of some derivatives of tetracycline and nonsteroid anti-inflammatory drugs towards dengue virus. Trop Biomed 2013; 30:681–690.
Rothan HA, Mohamed Z, Paydar M, Rahman NA, Yusof R. Inhibitory effect of doxy cycline against dengue virus replication in vitro. Arch Virol 2014; 159:711–718.
Yang JM, Chen YF, Tu YY, Yen KR, Yang YL. Combinatorial computational approaches to identify tetracycline derivatives as flavi-virus inhibitors. PLoS ONE 2007; 2:e428.
Speer BS, Shoemaker NB, Salyers AA. Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance. Clin Microbiol Rev 1992; 5(4):387–399.
Zakeri B, Wright GD. Chemical biology of tetracycline antibiotics. Biochem Cell Biol 2008; 86:124–136.
Bharadwaja S, Leea KE, Dwivedib VD, Kanga SG. Computational insights into tetracyclines as inhibitors against SARS- CoV-2 Mpro via combinatorial molecular simulation calculations. Life Sci 2020; 257:118080.
Wang J. Fast identification of possible drug treatment of coronavirus disease-19 (COVID-19) through computational drug repurposing study. J Chem Inf Model 2020; 60:3277-3286.
Bhowmik D, Nandi R, Jagadeesan R, Kumar N, Prakash A, Kumar D. Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches. Infect Genet Evol 2020;84:104451.
Ren Y, Shu T, Wu D, Mu J, Wang C, Huang M, Han Y, Zhang XY, Zhou W, Qiu Y, Zhou X. The ORF3a protein of SARSCoV-2 induces apoptosis in cells. Cell Mol Immunol 2020; 18:1–3.
Ahmad I, Alam M, Saadi R, Mahmud S, Saadi E. Doxycycline and Hydroxychloroquine as treatment for high-risk COVID-19 patients: experience from case series of 54 patients in long-term care facilities. medR- xiv 2020; 05:18.20066902.
Roy SK, Kendrick D, Sadowitz BD, Gatto L, Snyder K, Satalin JM, Golub LM, Nieman G. Jack of all trades: pleiotropy and the application of chemically modified tetracycline-3 in sepsis and the acute respiratory distress syndrome (ARDS). Pharmacol Res 2011;64:580–589.
Alam MM, Mahmud S, Rahman MM, Simpson JA, Aggarwal S, Ahmed Z. Clinical outcomes of early treatment with doxycycline for 89 high-risk COVID-19 patients in long-term care facilities in New York. Cureus 2020;12:e9658.
Bonzano C, Borroni D, Lancia A, Bonzano E. Doxycycline: from ocular rosacea to COVID-19 anosmia. New insight into the coronavirus outbreak. Front Med (Lausanne). 2020; 7:200.
Cakir B. A novel approach to managing COVID-19 patients; results of lopinavir plus doxycycline cohort. Eur J Clin Microbiol Infect Dis 2021; 40:663-664.
Cag Y, Icten S, Isik-Goren B, Baysal NB, Bektas B, Selvi E, Ergen P, Aydin O, Ucisik AC, Yilmaz-Karadag F, Caskurlu H, Akarsu-Ayazoglu T, Kocoglu H, Uzman S, Nural-Pamukcu M, Arslan F, Bas G, Kalcioglu MT, Vahaboglu H. A novel approach to managing COVID-19 patients; results of lopinavir plus doxycycline cohort. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol 2021; 40:407-411.
Yates PA, Newman SA, Oshry LJ, Glassman RH, Leone AM, Reichel E. Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease. Ther Adv Respir Dis 2020;14:1753466620951053.
Chowdhury ATMM, Shahbaz M, Karim MR, Islam J, Guo D, He S. A Randomized trial of ivermectin doxycycline and hydroxychloroquine azithromycin therapy on COVID19 patients. Research Square 2020.
Malek AE, Granwehr BP. Doxycycline as an alternative to azithromycin in elderly patients. Int J Antimicrob Agents 2021;57:106168.
Malek AE, Granwehr BP, Kontoyiannis DP. Doxycycline as a potential partner of COVID-19 therapies. IDCases 2020;21: e00864.
Ohe M, Furuya K, Goudarzi H. Tetracycline plus macrolide: A potential therapeutic regimen for COVID-19? BioScience Trends. 2020; 14:467-468.
Byrne JD, Shakur R, Collins JE, Becker S , Young CC, Boyce H, Traverso G. Prophylaxis with tetracyclines in ARDS: potential therapy for COVID-19-induced ARDS?. medRxiv 2020.
Gironi LC, Damiani G, Zavattaro E, Pacifico A, Santus P, Pigatto PDM, Cremona O, Savoia P. Tetracyclines in COVID-19 patients quarantined at home: literature evidence supporting real world data from a multicenter observational study targeting inflammatory and infectious dermatoses. Dermatol Ther 2020;22: e14694.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395:1054–1062.
Publicado
2021-07-31
Cómo citar
Mosquera-Sulbarán, J., Pedreañez, A., Callejas , D., & Carrero, Y. (2021). Tetraciclinas: ¿Antibióticos de uso potencial en la COVID-19? Tetracyclines: antibiotics of potential use in Covid-19?. Investigación Clínica, 62, 69-84. https://doi.org/10.22209/IC.v62s2a06
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