Deciphering the Potential Therapeutic Intervention Points of 2019-nCoV: A Pharmacological Perspective

Asma Khurshid, Rashid Amin, Athar Aziz, Omema Ahmed, Mahmoud E. F. Abdel-Haliem

Abstract


The emerging and re-emergence of viral outbreaks in the history of mankind has always pose severe global intimidation to public health and economy. The debilitating effects of 2019-nCoV (2019 novel coronavirus) outbreak has swiftly spread worldwide due to its highly contagious nature with severe risk of respiratory tract infections and higher mortality rate, necessitating the urgent need for the production of effective vaccine and potential therapeutic agents. The active evolution of SARS-CoV-2 strain in different population and environment strive immense challenge against anti-viral therapeutic development based on viral pathogenicity. The potential FDA drugs are evaluated based on their known safety and efficacy with exceptional pharmacokinetic profiles for the treatment of nCoV-2019. Existing knowledge related to MERS-CoV and SARS-CoV epidemic has provided a better understanding to explore purposeful therapeutics strategies against novel coronavirus disease (COVID-19). To limited extend, the ongoing promising and hopeful treatments includes convalescent plasma therapy, remdesivir, lopinavir/ritonavir, ACE inhibitors, TMPRSS2 inhibitors, hydroxychloroquine, interferon, ribavirin, tocilizumab, and corticosteroids however clinical efficacy of some of them need to be validated in randomized clinical trials (RCTs). The global struggle to make a protected and successful Coronavirus immunization is finally proving to be fruitful. Although challenges such as strain variation resistant, possible side effects, adequate supply of vaccines to all countries and limited availability of second dose still diverting the option of possible efficacious therapeutics strategies to work alongside with vaccine development with improved efficacy and safety profile. This review is focused on the potential advancement in therapeutic approaches with possible repurposing of the available drugs and explores the current status of available vaccines with hope that these strategies found to be cogent in controlling SARS-CoV-2 outbreak.

Keywords: Coronavirus disease 2019 (COVID-19); Remdesivir; Therapeutics; Plasma therapy; Hydroxychloroquine; Anti-viral; Angiotensin-converting enzyme 2; Type II transmembrane serine protease     


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References


University JH (2021) Coronavirus Resource Center.

Wang H, Li X, Li T, Zhang S, Wang L, et al. The genetic sequence, origin, and diagnosis of SARS-CoV-2. Eur J Clin Microbiol Infect Dis, (2020).

Huang C, Wang Y, Li X, Ren L, Zhao J, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, (2020); 395(10223): 497-506.

Jean SS, Lee PI, Hsueh PR. Treatment options for COVID-19: The reality and challenges. J Microbiol Immunol Infect, (2020); 53(3): 436-443.

Zhou F, Yu T, Du R, Fan G, Liu Y, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, (2020); 395(10229): 1054-1062.

Cheng ZJ, Shan J. 2019 Novel coronavirus: where we are and what we know. Infection, (2020); 48(2): 155-163.

Zhao N, Zhou ZL, Wu L, Zhang XD, Han SB, et al. An update on the status of COVID-19: a comprehensive review. Eur Rev Med Pharmacol Sci, (2020); 24(8): 4597-4606.

Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents, (2020); 55(3): 105924.

Park SJ, Yu KM, Kim YI, Kim SM, Kim EH, et al. Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets. mBio, (2020); 11(3).

Epidemiology Working Group for Ncip Epidemic Response CCfDC, Prevention. [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. Zhonghua Liu Xing Bing Xue Za Zhi, (2020); 41(2): 145-151.

Hossein-Khannazer N, Shokoohian B, Shpichka A, Aghdaei HA, Timashev P, et al. Novel therapeutic approaches for treatment of COVID-19. J Mol Med (Berl), (2020); 98(6): 789-803.

Shanmugaraj B, Malla A, Phoolcharoen W. Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development. Pathogens, (2020); 9(2).

Elgamasy S, Kamel MG, Ghozy S, Khalil A, Morra ME, et al. First Case of Focal Epilepsy Associated with SARS-Coronavirus-2. J Med Virol, (2020).

Zeouk I, Bekhti K, Lorenzo-Morales J. From Wuhan to COVID-19 Pandemic: An Up-to-Date Review of Its Pathogenesis, Potential Therapeutics, and Recent Advances. Microorganisms, (2020); 8(6).

Chen N, Zhou M, Dong X, Qu J, Gong F, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, (2020); 395(10223): 507-513.

Gao Y, Yan L, Huang Y, Liu F, Zhao Y, et al. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science, (2020); 368(6492): 779-782.

Seah I, Su X, Lingam G. Revisiting the dangers of the coronavirus in the ophthalmology practice. Eye (Lond), (2020); 34(7): 1155-1157.

Chan JF, Kok KH, Zhu Z, Chu H, To KK, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect, (2020); 9(1): 221-236.

Sawicki SG, Sawicki DL. Coronavirus transcription: a perspective. Curr Top Microbiol Immunol, (2005); 28731-55.

Hussain A, Kaler J, Dubey AK. Emerging Pharmaceutical Treatments of Novel COVID-19: A Review. Cureus, (2020); 12(5): e8260.

Salvi R, Patankar P. Emerging pharmacotherapies for COVID-19. Biomed Pharmacother, (2020); 128110267.

Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, et al. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell, (2020); 181(2): 281-292 e286.

Forster P, Forster L, Renfrew C, Forster M. Phylogenetic network analysis of SARS-CoV-2 genomes. Proc Natl Acad Sci U S A, (2020); 117(17): 9241-9243.

Martinez MA. Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus. Antimicrob Agents Chemother, (2020); 64(5).

Pandey SC, Pande V, Sati D, Upreti S, Samant M. Vaccination strategies to combat novel corona virus SARS-CoV-2. Life Sci, (2020); 256117956.

Graham RL, Donaldson EF, Baric RS. A decade after SARS: strategies for controlling emerging coronaviruses. Nat Rev Microbiol, (2013); 11(12): 836-848.

Elhusseiny KM, Abd-Elshahed Abd-Elhay F, Kamel MG. Possible therapeutic agents for COVID-19: a comprehensive review. Expert Rev Anti Infect Ther, (2020).

Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature, (2016); 531(7594): 381-385.

Lo MK, Jordan R, Arvey A, Sudhamsu J, Shrivastava-Ranjan P, et al. GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses. Sci Rep, (2017); 743395.

Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, et al. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio, (2018); 9(2).

Gordon CJ, Tchesnokov EP, Feng JY, Porter DP, Gotte M. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. J Biol Chem, (2020); 295(15): 4773-4779.

Aditya K. P RS, Timir Tripathi. Rational Design of the Remdesivir Binding Site in the RNA-dependent RNA Polymerase of SARS-CoV-2: Implications for Potential Resistance. bioRxiv, (2020).

Wang M, Cao R, Zhang L, Yang X, Liu J, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res, (2020); 30(3): 269-271.

Choy KT, Wong AY, Kaewpreedee P, Sia SF, Chen D, et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res, (2020); 178104786.

Jonathan Grein MD, Norio Ohmagari MD, Daniel Shin MD, George Diaz MD, Erika Asperges MD, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med, (2020); 3822327-2336.

Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med, (2020); 382(10): 929-936.

Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med, (2017); 9(396).

Mehta N, Mazer-Amirshahi M, Alkindi N, Pourmand A. Pharmacotherapy in COVID-19; A narrative review for emergency providers. Am J Emerg Med, (2020).

Baranovich T, Wong SS, Armstrong J, Marjuki H, Webby RJ, et al. T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J Virol, (2013); 87(7): 3741-3751.

Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci, (2017); 93(7): 449-463.

De Clercq E. New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections. Chem Asian J, (2019); 14(22): 3962-3968.

Sissoko D, Laouenan C, Folkesson E, M'Lebing AB, Beavogui AH, et al. Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea. PLoS Med, (2016); 13(3): e1001967.

Chang Chen YZ, Jianying Huang, Ping Yin, Zhenshun Cheng, Jianyuan Wu, Song Chen, Yongxi Zhang, Bo Chen, Mengxin Lu, Yongwen Luo, Lingao Ju, Jingyi Zhang, Xinghuan Wang. Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial medRxiv (2020).

Shiraki K, Daikoku T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacol Ther, (2020); 209107512.

Bimonte S, Crispo A, Amore A, Celentano E, Cuomo A, et al. Potential Antiviral Drugs for SARS-Cov-2 Treatment: Preclinical Findings and Ongoing Clinical Research. In Vivo, (2020); 34(3 Suppl): 1597-1602.

Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, et al. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med, (2013); 19(10): 1313-1317.

Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci, (2020); 248117477.

Gul MH, Htun ZM, Shaukat N, Imran M, Khan A. Potential specific therapies in COVID-19. Ther Adv Respir Dis, (2020); 141753466620926853.

Elhusseiny KM, Abd-Elhay FA, Kamel MG. Possible therapeutic agents for COVID-19: a comprehensive review. Expert Rev Anti Infect Ther, (2020); 1-15.

Mubareka S, Leung V, Aoki FY, Vinh DC. Famciclovir: a focus on efficacy and safety. Expert Opin Drug Saf, (2010); 9(4): 643-658.

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, (2020); 181(2): 271-280.e278.

Zhou Y, Vedantham P, Lu K, Agudelo J, Carrion R, Jr., et al. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res, (2015); 11676-84.

Glowacka I, Bertram S, Müller MA, Allen P, Soilleux E, et al. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J Virol, (2011); 85(9): 4122-4134.

Aljofan M GA. COVID-19 treatment: the race against time. Electron J Gen Med, (2020); 17.

Yamamoto M, Matsuyama S, Li X, Takeda M, Kawaguchi Y, et al. Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay. Antimicrob Agents Chemother, (2016); 60(11): 6532-6539.

Chan JF, Yao Y, Yeung ML, Deng W, Bao L, et al. Treatment With Lopinavir/Ritonavir or Interferon-beta1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset. J Infect Dis, (2015); 212(12): 1904-1913.

Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses – drug discovery and therapeutic options. Nat Rev Drug Discov, (2016); 15(5): 327-347.

Moyle GJ, Back D. Principles and practice of HIV-protease inhibitor pharmacoenhancement. HIV Med, (2001); 2(2): 105-113.

Arabi YM, Alothman A, Balkhy HH, Al-Dawood A, AlJohani S, et al. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-beta1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials, (2018); 19(1): 81.

Yang X, Yu Y, Xu J, Shu H, Xia J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med, (2020); 8(5): 475-481.

Kuba K, Imai Y, Rao S, Gao H, Guo F, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med, (2005); 11(8): 875-879.

Sun ML, Yang JM, Sun YP, Su GH. [Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi, (2020); 43(0): E014.

Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, et al. Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Cell, (2020); 181(4): 905-913.e907.

Lukassen S, Chua RL, Trefzer T, Kahn NC, Schneider MA, et al. SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. Embo j, (2020); 39(10): e105114.

Z.-X. WEI T-TT, S.-P. JIANG. The antiviral mechanisms, effects, safety and adverse effects of chloroquine. European Review for Medical and Pharmacological Sciences (2020); 247164-7172.

Plantone D, Koudriavtseva T. Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neoplastic, and Neurological Diseases: A Mini-Review. Clin Drug Investig, (2018); 38(8): 653-671.

Andrea Savarino LDT, Isabella Donatelli, Roberto Cauda, Antonio Cassone. New insights into the antiviral effects of chloroquine. Lancet Infect Dis (2006); 6767–69.

Shibata M, Aoki H, Tsurumi T, Sugiura Y, Nishiyama Y, et al. Mechanism of uncoating of influenza B virus in MDCK cells: action of chloroquine. J Gen Virol, (1983); 64(Pt 5): 1149-1156.

Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis, (2005); 24(1): 44-46.

Joshi SR, Butala N, Patwardhan MR, Daver NG, Kelkar D. Low cost anti-retroviral options: chloroquine based ARV regimen combined with hydroxyurea and lamivudine: a new economical triple therapy. J Assoc Physicians India, (2004); 52597-598.

Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis, (2003); 3(11): 722-727.

Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun, (2004); 323(1): 264-268.

Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J, (2005); 269.

Kearney JE. Chloroquine as a Potential Treatment and Prevention Measure for the 2019 Novel Coronavirus: A Review. J Chem Inf, (2020); 531689–1699.

Xue J, Moyer A, Peng B, Wu J, Hannafon BN, et al. Chloroquine is a zinc ionophore. PLoS One, (2014); 9(10): e109180.

Yao X, Ye F, Zhang M, Cui C, Huang B, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis, (2020).

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents, (2020); 105949.

Toumi M, Aballea S. Commentary on "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open label non-randomized clinical trial" by Gautret et al. J Mark Access Health Policy, (2020); 8(1): 1758390.

Juurlink DN. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. CMAJ, (2020); 192(17): E450-E453.

Heidary F, Gharebaghi R. Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. J Antibiot (Tokyo), (2020); 1-10.

Şimşek Yavuz S, Ünal S. Antiviral treatment of COVID-19. Turk J Med Sci, (2020); 50(Si-1): 611-619.

Thompson BT. Glucocorticoids and acute lung injury. Crit Care Med, (2003); 31(4 Suppl): S253-257.

Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant, (2020); 39(5): 405-407.

Yin Wang WJ, , Qi He,, Cheng Wang, , Baoju Liu, , Pan Zhou, , Nianguo Dong, Qiaoxia Tong. Early, low-dose and short-term application of corticosteroid treatment in patients with severe COVID-19 pneumonia: single-center experience from Wuhan, China. medRxiv, (2020).

Roberts M (2020) Coronavirus: Dexamethasone proves first life-saving drug. Health editor, BBC News online: BBC News. pp. June.

Ledford H (2020) Coronavirus breakthrough: dexamethasone is first drug shown to save lives. Nature.

Jarvis LM (2020) Dexamethasone appears to help severe cases of COVID-19. Chemical & Engineering News: Infectious disease

Abdolahi N, Kaheh E, Golsha R, Khodabakhshi B, Norouzi A, et al. Letter to the editor: efficacy of different methods of combination regimen administrations including dexamethasone, intravenous immunoglobulin, and interferon-beta to treat critically ill COVID-19 patients: a structured summary of a study protocol for a randomized controlled trial. Trials, (2020); 21(1): 549.

T C Theoharides 1 2 3 PC. Dexamethasone for COVID-19? Not So Fast J Biol Regul Homeost Agents, , (2020); 34(3).

Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest, (2020); 130(4): 1545-1548.

Duan K, Liu B, Li C, Zhang H, Yu T, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A, (2020); 117(17): 9490-9496.

Zhiqiang Zheng VMM, Sebastian Maurer-Stroh, Chow Wenn Yew, Carol Leong, Nur Khairiah Mohd-Ismail, Suganya Cheyyatraivendran Arularasu, Vincent Tak, Kwong Chow, Raymond Lin Tzer Pin, Ali Mirazimi,, Wanjin Hong, Yee-Joo Tan Monoclonal antibodies for the S2 subunit of spike of SARS-CoV cross-react with the newly-emerged SARS-CoV-2. bioRxiv, (2020).

Shen C, Wang Z, Zhao F, Yang Y, Li J, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA, (2020).

Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med, (2020); 26(6): 845-848.

Casadevall A, Joyner MJ, Pirofski LA. A Randomized Trial of Convalescent Plasma for COVID-19-Potentially Hopeful Signals. Jama, (2020).

Lu CC, Chen MY, Lee WS, Chang YL. Potential therapeutic agents against COVID-19: What we know so far. J Chin Med Assoc, (2020); 83(6): 534-536.

Bakker AB, Marissen WE, Kramer RA, Rice AB, Weldon WC, et al. Novel human monoclonal antibody combination effectively neutralizing natural rabies virus variants and individual in vitro escape mutants. J Virol, (2005); 79(14): 9062-9068.

Zhang B, Liu S, Tan T, Huang W, Dong Y, et al. Treatment With Convalescent Plasma for Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Chest, (2020).

Ahn JY, Sohn Y, Lee SH, Cho Y, Hyun JH, et al. Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea. J Korean Med Sci, (2020); 35(14): e149.

van Griensven J, Edwards T, de Lamballerie X, Semple MG, Gallian P, et al. Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea. N Engl J Med, (2016); 374(1): 33-42.

Shepard HM, Phillips GL, C DT, Feldmann M. Developments in therapy with monoclonal antibodies and related proteins. Clin Med (Lond), (2017); 17(3): 220-232.

Jiang L, Wang N, Zuo T, Shi X, Poon KM, et al. Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein. Sci Transl Med, (2014); 6(234): 234ra259.

Coughlin MM, Prabhakar BS. Neutralizing human monoclonal antibodies to severe acute respiratory syndrome coronavirus: target, mechanism of action, and therapeutic potential. Rev Med Virol, (2012); 22(1): 2-17.

Jia HP, Look DC, Shi L, Hickey M, Pewe L, et al. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J Virol, (2005); 79(23): 14614-14621.

De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med, (2012); 367(25): 2385-2395.

Le RQ, Li L, Yuan W, Shord SS, Nie L, et al. FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome. Oncologist, (2018); 23(8): 943-947.

Abidi E, El Nekidy WS, Alefishat E, Rahman N, Petroianu GA, et al. Tocilizumab and COVID-19: Timing of Administration and Efficacy. Front Pharmacol, (2022); 13825749.

Toniati P, Piva S, Cattalini M, Garrafa E, Regola F, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy. Autoimmun Rev, (2020); 19(7): 102568.

Luo P, Liu Y, Qiu L, Liu X, Liu D, et al. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol, (2020); 92(7): 814-818.

Chan JF, Chan KH, Kao RY, To KK, Zheng BJ, et al. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J Infect, (2013); 67(6): 606-616.

Hart BJ, Dyall J, Postnikova E, Zhou H, Kindrachuk J, et al. Interferon-beta and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays. J Gen Virol, (2014); 95(Pt 3): 571-577.

Saha RK, Takahashi T, Suzuki T. Glucosyl hesperidin prevents influenza a virus replication in vitro by inhibition of viral sialidase. Biol Pharm Bull, (2009); 32(7): 1188-1192.

Li C, Schluesener H. Health-promoting effects of the citrus flavanone hesperidin. Crit Rev Food Sci Nutr, (2017); 57(3): 613-631.

Katherine J. Wu CZaJC (2021) Coronavirus Drug and Treatment Tracker. US: The NewYork Times.

Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol, (2020); 20(6): 363-374.

Czaplewski L, Bax R, Clokie M, Dawson M, Fairhead H, et al. Alternatives to antibiotics-a pipeline portfolio review. Lancet Infect Dis, (2016); 16(2): 239-251.

Lim CC, Woo PCY, Lim TS. Development of a Phage Display Panning Strategy Utilizing Crude Antigens: Isolation of MERS-CoV Nucleoprotein human antibodies. Sci Rep, (2019); 9(1): 6088.

Wojewodzic MW. Bacteriophages Could Be a Potential Game Changer in the Trajectory of Coronavirus Disease (COVID-19). PHAGE: Therapy, Applications, and Research (2020); 160-65.

data Owi (2021) The Our World in Data COVID vaccination data. US: University of Oxford.

TRACKER C-V (2021) COVID-19 VACCINE TRACKER. COVID-19 VACCINE TRACKER.

Koop A (2020) Tracking COVID-19 Vaccines Around the World. Visual Capitalist.

Bloomberg (2021) More Than 359 Million Shots Given: Covid-19 Tracker. Bloomberg.

Bloomberg (2021) More Than 124 Million Shots Given: Covid-19 Tracker. Bloomberg.

Jones A (2021) Moderna Developing Booster Shot for New Virus Variant B.1.351. US: The Scientist.

Carl Zimmer JCaS-LW (2021) Coronavirus Vaccine Tracker. US: The NewYork Times.

Carl Zimmer JCaS-LW (2021) Coronavirus Vaccine Tracker. NewYork.

Cameron Appel DB, Daniel Gavrilov, Charlie Giattino, Joe Hasell, Bobbie Macdonald, Edouard Mathieu, Esteban Ortiz-Ospina, Hannah Ritchie, Lucas Rodés-Guirao, Max Roser (2021) Data on COVID-19 (coronavirus) by Our World in Data. England: Our World in Data.

Maxouris REaC (2021) What we know and don't know about the Omicron variant. UK: CNN Health.

trtworld (2021) Two cases of Omicron variant detected in Britain – latest updates. 27 Nov 21 ed.

Fox M (2021) Coronavirus variants: Here's what we know. 1 Dec 2021 ed. Uk: CNN Health.

Ledford ECH (2021) How bad is Omicron? What scientists know so far. US: Nature.

Rob Picheta C (2021) The first cases of the Omicron variant identified around the world. London: CNN.


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