JAK-STAT Pathway Inhibition and their Implications in COVID-19 Therapy

References

• Seif F, Aazami H, Khoshmirsafa M, et al. JAK inhibition as a new treatment strategy for patients with COVID-19. Int Arch Allergy Immunol. 2020;181:467–475.
   PubMed Web of Science ®Google Scholar
• Banerjee S, Biehl A, Gadina M, et al. JAK–STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs. 2017;77:521–546.
   PubMed Web of Science ®Google Scholar
• Billing U, Jetka T, Nortmann L, et al. Robustness and information transfer within IL-6-induced JAK/STAT signalling. Commun Biol. 2019;2:27.
   PubMed Web of Science ®Google Scholar
• Zhang J-M, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007;45:27–37.
   PubMedGoogle Scholar
• Ragab D, Eldin SH, Taeimah M, et al. The COVID-19 cytokine storm; what we know so far. Front Immunol. 2020;11:1446.
   PubMed Web of Science ®Google Scholar
• Lacy P, Stow JL. Cytokine release from innate immune cells: association with diverse membrane trafficking pathways. Blood. 2011;118:9–18.
   PubMed Web of Science ®Google Scholar
• Wang J, Jiang M, Chen X, et al. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol. 2020;108:17–41.
   PubMed Web of Science ®Google Scholar
• Chen L, Deng H, Cui H, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018;9:7204–7218.
   PubMedGoogle Scholar
• Hojyo S, Uchida M, Tanaka K, et al. How COVID-19 induces cytokine storm with high mortality. Inflamm Regen. 2020;40. DOI:10.1186/s41232-020-00146-3.
   PubMed Web of Science ®Google Scholar
• Thevarajan I, Buising KL, Cowie BC. Clinical presentation and management of COVID-19. Med J Aust. 2020;213:134–139.
   PubMed Web of Science ®Google Scholar
• Zhao M. Cytokine storm and immunomodulatory therapy in COVID-19: role of chloroquine and anti-IL-6 monoclonal antibodies. Int J Antimicrob Agents. 2020;55:91–98.
   Web of Science ®Google Scholar
• Bhaskar S, Sinha A, Banach M, et al. Cytokine storm in COVID-19—immunopathological mechanisms, clinical considerations, and therapeutic approaches: the REPROGRAM consortium position paper. Front Immunol. 2020;11:1648.
   PubMed Web of Science ®Google Scholar
• Satarker S, Nampoothiri M. Structural proteins in severe acute respiratory syndrome Coronavirus-2. Arch Med Res. 2020;51:482–491.
   PubMed Web of Science ®Google Scholar
• Castelli V, Cimini A, Ferri C. Cytokine storm in COVID-19: “when you come out of the storm, you won’t be the same person who walked in”. Front Immunol. 2020;11:2132.
   PubMed Web of Science ®Google Scholar
• Zeng F, Huang Y, Guo Y, et al. Association of inflammatory markers with the severity of COVID-19: a meta-analysis. Int J Infect Dis. 2020;96:467–474.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Fu B, Zheng X, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. Natl. Sci. Rev. 2020;7:998-1002.
   Google Scholar
• Kong M, Zhang H, Cao X, et al. Higher level of neutrophil-to-lymphocyte is associated with severe COVID-19. Epidemiol Infect. 2020;148:1–6.
   Web of Science ®Google Scholar
• Yan X, Li F, Wang X, et al. Neutrophil to lymphocyte ratio as prognostic and predictive factor in patients with coronavirus disease 2019: a retrospective cross‐sectional study. J Med Virol. 2020;92:2573–2581.
   PubMed Web of Science ®Google Scholar
• Pimentel GD, Dela Vega MCM, Laviano A. High neutrophil to lymphocyte ratio as a prognostic marker in COVID-19 patients. Clin Nutr ESPEN. 2020;84:106504.
   Google Scholar
• Feng X, Li S, Sun Q, et al. Immune-inflammatory parameters in COVID-19 cases: a systematic review and meta-analysis. Front Med. 2020;7:301.
   Web of Science ®Google Scholar
• Satarker S, Nampoothiri M. Involvement of the nervous system in COVID-19: the bell should toll in the brain. Life Sci. 2020;262:118568.
   PubMed Web of Science ®Google Scholar
• Abdin SM, Elgendy SM, Alyammahi SK, et al. Tackling the cytokine storm in COVID-19, challenges and hopes. Life Sci. 2020;257:118054.
   PubMed Web of Science ®Google Scholar
• Domingo P, Mur I, Pomar V, et al. The four horsemen of a viral Apocalypse: the pathogenesis of SARS-CoV-2 infection (COVID-19). EBioMedicine. 2020;58:102887.
   PubMed Web of Science ®Google Scholar
• Rockx B, Kuiken T, Herfst S, et al. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science. 2020;368:1012–1015.
   PubMed Web of Science ®Google Scholar
• Kao KC, Hu HC, Chang CH, et al. Diffuse alveolar damage associated mortality in selected acute respiratory distress syndrome patients with open lung biopsy. Crit Care. 2015;19:228.
   PubMed Web of Science ®Google Scholar
• Tian S, Hu W, Niu L, et al. Pulmonary pathology of early-phase 2019 Novel Coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thorac Oncol. 2020;15:700–704.
   PubMed Web of Science ®Google Scholar
• Borczuk AC, Salvatore SP, Seshan SV, et al. COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Italy and New York City. Mod Pathol. 2020. DOI:10.1038/s41379-020-00661-1.
   PubMed Web of Science ®Google Scholar
• Jeffers SA, Tusell SM, Gillim-Ross L, et al. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc Natl Acad Sci. 2004;101:15748–15753.
   PubMed Web of Science ®Google Scholar
• Chen Y, Chan VSF, Zheng B, et al. A novel subset of putative stem/progenitor CD34+ Oct-4 + cells is the major target for SARS coronavirus in human lung. J Exp Med. 2007;204:2529–2536.
   PubMed Web of Science ®Google Scholar
• Yu F, Jia R, Tang Y, et al. SARS-CoV-2 infection and stem cells: interaction and intervention. Stem Cell Res. 2020;46:101859.
   PubMed Web of Science ®Google Scholar
• Shin D, Mukherjee R, Grewe D, et al. Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature. 2020;587:657–662.
   PubMed Web of Science ®Google Scholar
• Mondal R, Lahiri D, Deb S, et al. COVID-19: are we dealing with a multisystem vasculopathy in disguise of a viral infection? J Thromb Thrombolysis. 2020;50:567–579.
   PubMed Web of Science ®Google Scholar
• Emameh RZ, Nosrati H, Eftekhari M, et al. Expansion of single cell transcriptomics data of SARS-CoV infection in human bronchial epithelial cells to COVID-19. Biol Proced Online. 2020;22:16.
   PubMed Web of Science ®Google Scholar
• Gao Y‐M, Xu G, Wang B, et al. Cytokine storm syndrome in coronavirus disease 2019: a narrative review. J Intern Med. 2020. DOI:10.1111/joim.13144.
   PubMed Web of Science ®Google Scholar
• Ziegler CGK, Allon SJ, Nyquist SK, et al. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell. 2020;181:1016–1035.
   PubMed Web of Science ®Google Scholar
• Jafarzadeh A, Chauhan P, Saha B, et al. Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: lessons from SARS and MERS, and potential therapeutic interventions. Life Sci. 2020;257:118102.
   PubMed Web of Science ®Google Scholar
• McCray PB, Pewe L, Wohlford-Lenane C, et al. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol. 2007;81:813–821.
   PubMed Web of Science ®Google Scholar
• Bao L, Deng W, Huang B, et al. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature. 2020;583:830–833.
   PubMed Web of Science ®Google Scholar
• Jiang R-D, Liu M-Q, Chen Y, et al. Pathogenesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme 2. Cell. 2020;182:50–58.
   PubMed Web of Science ®Google Scholar
• Winkler ES, Bailey AL, Kafai NM, et al. SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function. Nat Immunol. 2020;21:1327-1335.
   Web of Science ®Google Scholar
• Park MD. Macrophages: a Trojan horse in COVID-19? Nat Rev Immunol. 2020;20:351.
   PubMedGoogle Scholar
• Thomas G, Frederick E, Hausburg M, et al. The novel immunomodulatory biologic LMWF5A for pharmacological attenuation of the “cytokine storm” in COVID-19 patients: a hypothesis. Patient Saf Surg. 2020;14:21.
   PubMed Web of Science ®Google Scholar
• Rael LT, Bar-Or R, Banton KL, et al. The anti-inflammatory effect of LMWF5A and N-acetyl kynurenine on macrophages: involvement of aryl hydrocarbon receptor in mechanism of action. Biochem Biophys Reports. 2018;15:61–67.
   PubMedGoogle Scholar
• Market M, Angka L, Martel AB, et al. Flattening the COVID-19 curve with natural killer cell based immunotherapies. Front Immunol. 2020;11:1512.
   PubMed Web of Science ®Google Scholar
• Guillon A, Hiemstra PS, Si-Tahar M. Pulmonary immune responses against SARS-CoV-2 infection: harmful or not? Intensive Care Med. 2020;46:1897–1900.
   PubMed Web of Science ®Google Scholar
• Popov D. Treatment of Covid-19 infection. A rationale for current and future pharmacological approach. Ec Pulmonol Respir Med. 2020;9:38–58.
   Google Scholar
• Mathew D, Giles JR, Baxter AE, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science. 2020;1209:eabc8511.
   Web of Science ®Google Scholar
• Iqbal H. The importance of cell-mediated immunity in COVID-19 – an opinion. Med Hypotheses. 2020;143:110152.
   PubMed Web of Science ®Google Scholar
• Polycarpou A, Howard M, Farrar CA, et al. Rationale for targeting complement in COVID‐19. EMBO Mol Med. 2020;12:e12642.
   PubMed Web of Science ®Google Scholar
• Kuchipudi SV. The complex role of STAT3 in viral infections. J Immunol Res. 2015;2015:272359.
   PubMed Web of Science ®Google Scholar
• Wen W, Su W, Tang H, et al. Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing. Cell Discov. 2020;6:31.
   PubMed Web of Science ®Google Scholar
• Orr MT, Lanier LL. Natural killer cell education and tolerance. Cell. 2010;142:847–856.
   PubMed Web of Science ®Google Scholar
• Pérez GTL, Sandoval M de LPR, Altamiranoew MST. Evaluation of immune response, comorbidities and immunomodulation in SARS-CoV2 pandemic. EC Paediatr. 2020;9:70–90.
   Google Scholar
• Yang D, Chu H, Hou Y, et al. Attenuated interferon and proinflammatory response in SARS-CoV-2-infected human dendritic cells is associated with viral antagonism of STAT1 phosphorylation. J Infect Dis. 2020;222:734–745.
   PubMed Web of Science ®Google Scholar
• Gotthardt D, Trifinopoulos J, Sexl V, et al. JAK/STAT cytokine signaling at the crossroad of NK cell development and maturation. Front Immunol. 2019;10:2590.
   PubMed Web of Science ®Google Scholar
• O’Shea JJ, Plenge R. JAKs and STATs in immunoregulation and immune-mediated disease. Immunity. 2013;36:542–550.
   Web of Science ®Google Scholar
• Meletiadis J, Tsiodras S, Tsirigotis P. Interleukin-6 blocking vs. JAK-STAT inhibition for prevention of lung injury in patients with COVID-19. Infect Dis Ther. 2020;9:707–713.
   PubMed Web of Science ®Google Scholar
• Bouwman W, Verhaegh W, Holtzer L, et al. Measurement of cellular immune response to viral infection and vaccination. Front Immunol. 2020;11:1–13.
   PubMed Web of Science ®Google Scholar
• Rojas P, Sarmiento M. JAK/STAT pathway inhibition may be a promising therapy for COVID-19-related hyperinflammation in hematologic patients. Acta Haematol. 2020; [cited 2020 Nov 18]:1-5. DOI:10.1159/000510179
   PubMed Web of Science ®Google Scholar
• Claverie J-M. A putative role of de-mono-ADP-ribosylation of STAT1 by the SARS-CoV-2 Nsp3 protein in the cytokine storm syndrome of COVID-19. Viruses. 2020;12:646.
   PubMed Web of Science ®Google Scholar
• Khan SA, Zia K, Ashraf S, et al. Identification of chymotrypsin-like protease inhibitors of SARS-CoV-2 via integrated computational approach. J Biomol Struct Dyn. 2020;[cited 2020 May 29]:1–10. DOI:10.1080/07391102.2020.1751298
   Web of Science ®Google Scholar
• Prasad S, Potdar V, Cherian S, et al. Transmission electron microscopy imaging of SARS-CoV-2. Indian J Med Res. 2020;151:241–243.
   PubMed Web of Science ®Google Scholar
• Satarker S, Ahuja T, Banerjee M, et al. Hydroxychloroquine in COVID-19: potential mechanism of action against SARS-CoV-2. Curr Pharmacol Rep. 2020;6:203–211.
   PubMedGoogle Scholar
• Xu J, Lazartigues E. Expression of ACE2 in human neurons supports the neuro-invasive potential of COVID-19 virus. Cell Mol Neurobiol. 2020;[cited 2020 Aug 13]:1–5. DOI:10.1007/s10571-020-00915-1
   PubMed Web of Science ®Google Scholar
• Vollono C, Rollo E, Romozzi M, et al. Focal status epilepticus as unique clinical feature of COVID-19: a case report. Seizure Eur J Epilepsy. 2020;78:109–112.
   PubMed Web of Science ®Google Scholar
• Catanzaro M, Fagiani F, Racchi M, et al. Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal Transduct Target Ther. 2020;5:84.
   PubMed Web of Science ®Google Scholar
• Wang N, Shang J, Jiang S, et al. Subunit vaccines against emerging pathogenic human coronaviruses. Front Microbiol. 2020;11:298.
   PubMed Web of Science ®Google Scholar
• Guo Y-R, Cao Q-D, Hong Z-S, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Mil Med Res. 2020;7:11.
   PubMed Web of Science ®Google Scholar
• Klemm T, Ebert G, Calleja DJ, et al. Mechanism and inhibition of the papain‐like protease, PLpro, of SARS‐CoV‐2. Embo J. 2020;39:1–17.
   Web of Science ®Google Scholar
• Silva-lópez RE. The main protease of SARS-CoV-2 as therapeutic target to development specific drugs to treat COVID-19. J. Appl.Biotechnol.Bioeng.Rev. 2020;7:185-189.
   Google Scholar
• Stancioiu F, Papadakis G, Kteniadakis S, et al. A dissection of SARS‑CoV2 with clinical implications (Review). Int J Mol Med. 2020;46:489–508.
   PubMed Web of Science ®Google Scholar
• Xia H, Cao Z, Xie X, et al. Evasion of Type I Interferon by SARS-CoV-2. Cell Rep. 2020;33:108234.
   PubMed Web of Science ®Google Scholar
• Astuti IY. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2): an overview of viral structure and host response. Diabetes Metab Syndr Clin Res Rev. 2020;14:407–412.
   PubMed Web of Science ®Google Scholar
• Wu Y, Ma L, Zhuang Z, et al. Main protease of SARS-CoV-2 serves as a bifunctional molecule in restricting type I interferon antiviral signaling.Vol. 5. Signal Transduct Target Ther. 2020;5:221.
   PubMed Web of Science ®Google Scholar
• Prescott L. SARS-CoV-2 3CLpro whole human proteome cleavage prediction and enrichment/depletion analysis. bioRxiv Prepr. 2020;[cited 2020 Nov 17]. DOI:10.1101/2020.08.24.265645.
   Google Scholar
• Mu J, Fang Y, Yang Q, et al. SARS-CoV-2 N protein antagonizes type I interferon signaling by suppressing phosphorylation and nuclear translocation of STAT1 and STAT2. Cell Discov. 2020;6:65.
   PubMed Web of Science ®Google Scholar
• Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020;20:355–362.
   PubMed Web of Science ®Google Scholar
• Alhammad YMO, Fehr AR. The viral macrodomain counters host antiviral ADP-ribosylation. Viruses. 2020;12:384.
   PubMed Web of Science ®Google Scholar
• Scarno G, Pietropaolo G, Di Censo C, et al. Transcriptional, epigenetic and pharmacological control of JAK/STAT pathway in NK cells. Front Immunol. 2019;10:2456.
   PubMed Web of Science ®Google Scholar
• Hong Y, Xin C, Zheng H, et al. miR-365a-3p regulates ADAM10-JAK-STAT signaling to suppress the growth and metastasis of colorectal cancer cells. J Cancer. 2020;11:3634–3644.
   PubMed Web of Science ®Google Scholar
• Alunno A, Padjen I, Fanouriakis A, et al. Pathogenic and therapeutic relevance of JAK/STAT signaling in systemic lupus erythematosus: integration of distinct inflammatory pathways and the prospect of their inhibition with an oral agent. Cells. 2019;8:898.
   PubMed Web of Science ®Google Scholar
• Hammarén HM, Virtanen AT, Raivola J, et al. The regulation of JAKs in cytokine signaling and its breakdown in disease. Cytokine. 2019;118:48–63.
   PubMed Web of Science ®Google Scholar
• Croker BA, Kiu H, Nicholson SE. SOCS regulation of the JAK/STAT signalling pathway. Semin Cell Dev Biol. 2008;19:414–422.
   PubMed Web of Science ®Google Scholar
• Owen KL, Brockwell NK, Parker BS. JAK-STAT signaling: a double-edged sword of immune regulation and cancer progression. Cancers (Basel). 2019;11:2002.
   PubMed Web of Science ®Google Scholar
• Bousoik E, Montazeri Aliabadi H. “Do We Know Jack” about JAK? A closer look at JAK/STAT signaling pathway. Front Oncol. 2018;8:287.
   PubMed Web of Science ®Google Scholar
• Luo W, Li Y-X, Jiang L-J, et al. Targeting JAK-STAT signaling to control cytokine release syndrome in COVID-19. Trends Pharmacol Sci. 2020;41:531–543.
   PubMed Web of Science ®Google Scholar
• Wu D, Yang XO. TH17 responses in cytokine storm of COVID-19: an emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect. 2020;53:368–370.
   PubMedGoogle Scholar
• Bettelli E, Korn T, Oukka M, et al. Induction and effector functions of TH17 cells. Nature. 2008;453:1051–1057.
   PubMed Web of Science ®Google Scholar
• von Essen M, Søndergaard H, Petersen E, et al. IL-6, IL-12, and IL-23 STAT-pathway genetic risk and responsiveness of lymphocytes in patients with multiple sclerosis. Cells. 2019;8:285.
   PubMed Web of Science ®Google Scholar
• Duncan SA, Baganizi DR, Sahu R, et al. SOCS proteins as regulators of inflammatory responses induced by bacterial infections: a review. Front Microbiol. 2017;8:2431.
   PubMed Web of Science ®Google Scholar
• Liau NPD, Laktyushin A, Lucet IS, et al. The molecular basis of JAK/STAT inhibition by SOCS1. Nat Commun. 2018;9:1558.
   PubMed Web of Science ®Google Scholar
• Niu G-J, Xu J-D, Yuan W-J, et al. Protein inhibitor of activated STAT (PIAS) negatively regulates the JAK/STAT pathway by inhibiting STAT phosphorylation and translocation. Front Immunol. 2018;9:2392.
   PubMed Web of Science ®Google Scholar
• Shuai K. Regulation of cytokine signaling pathways by PIAS proteins. Cell Res. 2006;16:196–202.
   PubMed Web of Science ®Google Scholar
• Nakahira M, Tanaka T, Robson BE, et al. Regulation of signal transducer and activator of transcription signaling by the tyrosine phosphatase PTP-BL. Immunity. 2007;26:163–176.
   PubMed Web of Science ®Google Scholar
• Nian Q, Berthelet J, Zhang W, et al. T-cell protein tyrosine phosphatase is irreversibly inhibited by etoposide-quinone, a reactive metabolite of the chemotherapy drug etoposide. Mol Pharmacol. 2019;96:297–306.
   PubMed Web of Science ®Google Scholar
• Pike KA, Hutchins AP, Vinette V, et al. Protein tyrosine phosphatase 1B is a regulator of the interleukin-10-induced transcriptional program in macrophages. Sci Signal. 2014;7:ra43.
   PubMed Web of Science ®Google Scholar
• La Rosée F, Bremer HC, Gehrke I, et al. The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation. Leukemia. 2020;34:1805–1815.
   PubMed Web of Science ®Google Scholar
• Verstovsek S. Ruxolitinib: an oral janus kinase 1 and janus kinase 2 inhibitor in the management of myelofibrosis. Postgrad Med. 2013;125:128–135.
   PubMed Web of Science ®Google Scholar
• Capochiani E, Frediani B, Iervasi G, et al. Ruxolitinib rapidly reduces acute respiratory distress syndrome in COVID-19 disease. analysis of data collection from RESPIRE protocol. Front Med. 2020;7:466.
   Web of Science ®Google Scholar
• Cao Y, Wei J, Zou L, et al. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): a multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol. 2020;146:137–146.e3.
   PubMed Web of Science ®Google Scholar
• Zhang X, Zhang Y, Qiao W, et al. Baricitinib, a drug with potential effect to prevent SARS-COV-2 from entering target cells and control cytokine storm induced by COVID-19. Int Immunopharmacol. 2020;86:106749.
   PubMed Web of Science ®Google Scholar
• Cantini F, Niccoli L, Matarrese D, et al. Baricitinib therapy in COVID-19: a pilot study on safety and clinical impact. J Infect. 2020;81:318–356.
   PubMed Web of Science ®Google Scholar
• Tang JW, Young S, May S, et al. Comparing hospitalised, community and staff COVID-19 infection rates during the early phase of the evolving COVID-19 epidemic. J Infect. 2020;81:647–679.
   Web of Science ®Google Scholar
• Bronte V, Ugel S, Tinazzi E, et al. Baricitinib restrains the immune dysregulation in severe COVID-19 patients. J Clin Invest. 2020. DOI:10.1172/JCI141772.
   PubMed Web of Science ®Google Scholar
• Mehta P, Ciurtin C, Scully M, et al. JAK inhibitors in COVID-19: the need for vigilance regarding increased inherent thrombotic risk. Eur Respir J. 2020;56:2001919.
   PubMed Web of Science ®Google Scholar
• Dowty ME, Lin J, Ryder TF, et al. The pharmacokinetics, metabolism, and clearance mechanisms of tofacitinib, a janus kinase inhibitor, in humans. Drug Metab Dispos. 2014;42:759–773.
   PubMed Web of Science ®Google Scholar
• Miklossy G, Hilliard TS, Turkson J. Therapeutic modulators of STAT signalling for human diseases. Nat Rev Drug Discov. 2013;12:611–629.
   PubMed Web of Science ®Google Scholar
• Lau Y-T, Ramaiyer M, Johnson D, et al. Targeting STAT3 in cancer with nucleotide therapeutics. Cancers (Basel). 2019;11:1681.
   PubMed Web of Science ®Google Scholar
• Ni W, Yang X, Yang D, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care. 2020;24:422.
   PubMed Web of Science ®Google Scholar
• Gaspari V, Zengarini C, Greco S, et al. Side effects of ruxolitinib in patients with SARS-CoV-2 infection: two case reports. Int J Antimicrob Agents. 2020;56:106023.
   PubMed Web of Science ®Google Scholar
• Alberio L, Blum S, Martins F. Ruxolitinib in the treatment of polycythemia vera: patient selection and special considerations. J Blood Med. 2016;7:205–215.
   PubMed Web of Science ®Google Scholar
• Jorgensen SCJ, Tse CLY, Burry L, et al. Baricitinib: a review of pharmacology, safety, and emerging clinical experience in COVID‐19. Pharmacother J Hum Pharmacol Drug Ther. 2020;40:843–856.
   Google Scholar
• Harigai M. Growing evidence of the safety of JAK inhibitors in patients with rheumatoid arthritis. Rheumatology. 2019;58:i34–i42.
   PubMed Web of Science ®Google Scholar
• World Health Organization (WHO). WHO Coronavirus disease (COVID-19) dashboard. [cited 2020 Sept 03]. Available from: https://covid19.who.int/
   Google Scholar
• Gorbalenya AE, Baker SC, Baric RS, et al. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5:536–544.
   PubMed Web of Science ®Google Scholar
• World Health Organization (WHO). “Solidarity” clinical trial for COVID-19 treatments, 2020. [cited 2020 Sept 03]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments
   Google Scholar
• Mahalmani VM, Mahendru D, Semwal A, et al. COVID-19 pandemic: a review based on current evidence. Indian J Pharmacol. 2020;52:117–129.
   PubMed Web of Science ®Google Scholar
• Cherian SS, Agrawal M, Basu A, et al. Perspectives for repurposing drugs for the coronavirus disease 2019. Indian J Med Res. 2020;151:160–171.
   PubMed Web of Science ®Google Scholar