COVID-19 Therapeutic Options Under Investigation

Since its emergence in China in December 2019, COVID-19 has quickly spread around the globe causing a pandemic. Vaccination or the development of herd immunity seems the only way to slow down the spread of the virus; however, both are not achievable in the near future. Therefore, effective treatments to mitigate the burden of this pandemic and reduce mortality rates are urgently needed. Preclinical and clinical studies of potential antiviral and immunomodulatory compounds and molecules to identify safe and efficacious therapeutics for COVID-19 are ongoing. Two compounds, remdesivir, and dexamethasone have been so far shown to reduce COVID-19–associated death. Here, we provide a review of the potential therapeutic agents being considered for the treatment and management of COVID-19 patients.

[1]  Shibo Jiang,et al.  Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine , 2020, Cellular & Molecular Immunology.

[2]  T. Singhal.  A Review of Coronavirus Disease-2019 (COVID-19) , 2020, The Indian Journal of Pediatrics.

[3]  J. Hirschmann,et al.  Use of corticosteroids in treating infectious diseases. , 2008, Archives of internal medicine.

[4]  Yanchen Zhou,et al.  Protease inhibitors targeting coronavirus and filovirus entry , 2015, Antiviral Research.

[5]  R. Tiwari,et al.  COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics , 2020, Human vaccines & immunotherapeutics.

[6]  A. Moscona.  Neuraminidase inhibitors for influenza. , 2005, The New England journal of medicine.

[7]  O. Steward,et al.  Sphingosine-1-phosphate receptor antagonism enhances proliferation and migration of engrafted neural progenitor cells in a model of viral-induced demyelination. , 2015, The American journal of pathology.

[8]  Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) , 2020, Frontiers in Immunology.

[9]  M. Shimojima,et al.  Therapeutic effects of favipiravir against severe fever with thrombocytopenia syndrome virus infection in a lethal mouse model: Dose-efficacy studies upon oral administration , 2018, bioRxiv.

[10]  Tao Zhang,et al.  Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak , 2020, Current Biology.

[11]  Jian-Piao Cai,et al.  Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset , 2015, The Journal of infectious diseases.

[12]  L. Saravolatz,et al.  Nitazoxanide: a new thiazolide antiparasitic agent. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  D. Smee,et al.  The Synthetic Antiviral Drug Arbidol Inhibits Globally Prevalent Pathogenic Viruses , 2016, Journal of Virology.

[14]  A. Elfiky,et al.  Anti-HCV, nucleotide inhibitors, repurposing against COVID-19 , 2020, Life Sciences.

[15]  C. A. Koetzner,et al.  A Major Determinant for Membrane Protein Interaction Localizes to the Carboxy-Terminal Domain of the Mouse Coronavirus Nucleocapsid Protein , 2005, Journal of Virology.

[16]  Z. Hong,et al.  Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study , 2020, Journal of Infection.

[17]  Lixia Chen,et al.  Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods , 2020, Acta Pharmaceutica Sinica B.

[18]  P. Garcez,et al.  Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models , 2016, Viruses.

[19]  B. D. da Fonseca,et al.  Antiviral activity of chloroquine against dengue virus type 2 replication in Aotus monkeys. , 2015, Viral immunology.

[20]  R. Gasparini,et al.  Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study. , 2012, Vaccine.

[21]  G. Gao,et al.  A Novel Coronavirus from Patients with Pneumonia in China, 2019 , 2020, The New England journal of medicine.

[22]  Michel Theron,et al.  An interferon‐γ‐related cytokine storm in SARS patients† , 2004, Journal of medical virology.

[23]  Lisa E. Gralinski,et al.  Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses , 2017, Science Translational Medicine.

[24]  S. Harrison,et al.  Structure of SARS Coronavirus Spike Receptor-Binding Domain Complexed with Receptor , 2005, Science.

[25]  E. Ruderman,et al.  Interleukin 6 inhibition - RA and beyond. , 2011, Bulletin of the NYU hospital for joint diseases.

[26]  孝則 池田.  腸管糞線虫症治療薬イベルメクチン（ストロメクトール）の薬理作用 , 2003 .

[27]  Yan Zhao,et al.  Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. , 2020, JAMA.

[28]  Chengyu Jiang,et al.  SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway , 2008, Cell Research.

[29]  R. Schinazi,et al.  Characterization of beta-D-N-4-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus , 2022 .

[30]  R. Altman,et al.  PharmGKB summary: Macrolide antibiotic pathway, pharmacokinetics/pharmacodynamics , 2017, Pharmacogenetics and genomics.

[31]  H. Feldmann,et al.  Use of Favipiravir to Treat Lassa Virus Infection in Macaques , 2018, Emerging infectious diseases.

[32]  Giuliano Rizzardini,et al.  Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study , 2020, Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America.

[33]  Yi Wang,et al.  Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial , 2020, The Lancet.

[34]  Luna Yue Huang,et al.  The effect of large-scale anti-contagion policies on the COVID-19 pandemic , 2020, Nature.

[35]  Kwok-Hung Chan,et al.  Discovery of Seven Novel Mammalian and Avian Coronaviruses in the Genus Deltacoronavirus Supports Bat Coronaviruses as the Gene Source of Alphacoronavirus and Betacoronavirus and Avian Coronaviruses as the Gene Source of Gammacoronavirus and Deltacoronavirus , 2012, Journal of Virology.

[36]  J. R. Scotti,et al.  Available From , 1973 .

[37]  V. Volchkov,et al.  Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication , 2015, Viruses.

[38]  M. Kurusz,et al.  Efficacy and safety , 2021, Perfusion.

[39]  G. Gao,et al.  Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses , 2016, Trends in Microbiology.

[40]  Michelle M. Packard,et al.  Prior Infection and Passive Transfer of Neutralizing Antibody Prevent Replication of Severe Acute Respiratory Syndrome Coronavirus in the Respiratory Tract of Mice , 2004, Journal of Virology.

[41]  D. Earnshaw,et al.  Mode of antiviral action of penciclovir in MRC-5 cells infected with herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus , 1992, Antimicrobial Agents and Chemotherapy.

[42]  V. Kraus,et al.  Colchicine--Update on mechanisms of action and therapeutic uses. , 2015, Seminars in arthritis and rheumatism.

[43]  S. Johnston,et al.  Azithromycin induces anti-viral responses in bronchial epithelial cells , 2010, European Respiratory Journal.

[44]  J. Baillie,et al.  Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury , 2020, The Lancet.

[45]  S. Recalcati.  Cutaneous manifestations in COVID‐19: a first perspective , 2020, Journal of the European Academy of Dermatology and Venereology : JEADV.

[46]  D. Jans,et al.  Inhibitors of nuclear transport. , 2019, Current opinion in cell biology.

[47]  Sandro G. Viveiros Rosa,et al.  Clinical trials on drug repositioning for COVID-19 treatment , 2020, Revista panamericana de salud publica = Pan American journal of public health.

[48]  J. Peiris,et al.  Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003 , 2003, The Lancet.

[49]  M. Trojano,et al.  Gender differences in safety issues during Fingolimod therapy: Evidence from a real‐life Relapsing Multiple Sclerosis cohort , 2017, Brain and behavior.

[50]  D. Tuveson,et al.  Famotidine Use Is Associated With Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study , 2020, Gastroenterology.

[51]  Paul Garner,et al.  SARS: Systematic Review of Treatment Effects , 2006, PLoS medicine.

[52]  Thomas Jaki,et al.  Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report , 2020, The New England journal of medicine.

[53]  Nicholas C. Wu,et al.  A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV , 2020, Science.

[54]  F. Zoulim,et al.  Inhibition of hepatitis C virus replication by semi-synthetic derivatives of glycopeptide antibiotics , 2011, The Journal of antimicrobial chemotherapy.

[55]  Ying Zhu,et al.  Nuclear/nucleolar localization properties of C-terminal nucleocapsid protein of SARS coronavirus , 2005, Virus Research.

[56]  M. Bernardi,et al.  In vitro effect of thymosin‐α1 and interferon‐α on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C , 2001 .

[57]  M. Preobrazhenskaya,et al.  Polycyclic peptide and glycopeptide antibiotics and their derivatives as inhibitors of HIV entry , 2006, Antiviral Research.

[58]  C. Arias,et al.  Glycopeptides (Vancomycin and Teicoplanin), Streptogramins (Quinupristin-Dalfopristin), Lipopeptides (Daptomycin), and Lipoglycopeptides (Telavancin) , 2015 .

[59]  Pibao Li,et al.  Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study , 2020, The American journal of gastroenterology.

[60]  Zhìhóng Hú,et al.  Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro , 2020, Cell Discovery.

[61]  S. M. Raboni,et al.  Human coronavirus and severe acute respiratory infection in Southern Brazil , 2016, Pathogens and global health.

[62]  P. Bhargava,et al.  Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19 , 2020, International Journal of Infectious Diseases.

[63]  Xu Liu,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) , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[64]  Miriam Merad,et al.  Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages , 2020, Nature Reviews Immunology.

[65]  Md. Abdul Alim Al-Bari.  Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases , 2017, Pharmacology research & perspectives.

[66]  M. Seong,et al.  In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses , 2020, The Korean journal of internal medicine.

[67]  D. Tuveson,et al.  Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series , 2020, Gut.

[68]  Jongdae Lee,et al.  Enhancement of the infectivity of SARS-CoV in BALB/c mice by IMP dehydrogenase inhibitors, including ribavirin , 2006, Antiviral Research.

[69]  Marc Van Ranst,et al.  In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine , 2004, Biochemical and Biophysical Research Communications.

[70]  P. Rottier,et al.  Molecular Interactions in the Assembly of Coronaviruses , 2005, Advances in Virus Research.

[71]  F. Hayden,et al.  Influenza virus polymerase inhibitors in clinical development , 2019, Current opinion in infectious diseases.

[72]  Guo‐Jun Zhang,et al.  Factors associated with prolonged viral shedding and impact of lopinavir/ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection , 2020, European Respiratory Journal.

[73]  A. Osterhaus,et al.  Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. , 2012, The New England journal of medicine.

[74]  S. Lofgren,et al.  Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 , 2020, Annals of Internal Medicine.

[75]  L. Leibovici,et al.  Comparative Efficacy and Safety of Vancomycin versus Teicoplanin: Systematic Review and Meta-Analysis , 2009, Antimicrobial Agents and Chemotherapy.

[76]  Hui Guo,et al.  First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab , 2020, Blood Advances.

[77]  B. D. da Fonseca,et al.  Chloroquine Inhibits Dengue Virus Type 2 Replication in Vero Cells but Not in C6/36 Cells , 2013, TheScientificWorldJournal.

[78]  R. Shrestha,et al.  Combined Intravitreal Bevacizumab And Dexamethasone In Bilateral Lupus Retinopathy , 2019, International medical case reports journal.

[79]  D. Jans,et al.  Nuclear trafficking of proteins from RNA viruses: potential target for antivirals? , 2012, Antiviral research.

[80]  M. Sierra Vega,et al.  The Pharmacokinetics and Interactions of Ivermectin in Humans—A Mini-review , 2008, The AAPS journal.

[81]  R. K. Robins,et al.  Broad-Spectrum Antiviral Activity of Virazole: 1-f8- D-Ribofuranosyl- 1,2,4-triazole- 3-carboxamide , 1972, Science.

[82]  Christian Drosten,et al.  Identification of a novel coronavirus in patients with severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[83]  J. Sung,et al.  Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome , 2004, Clinical and experimental immunology.

[84]  P. Mehta,et al.  COVID-19: consider cytokine storm syndromes and immunosuppression , 2020, The Lancet.

[85]  H. Doerr,et al.  Treatment of SARS with human interferons , 2003, The Lancet.

[86]  B. Berkhout,et al.  Inhibition of Human Coronavirus NL63 Infection at Early Stages of the Replication Cycle , 2006, Antimicrobial Agents and Chemotherapy.

[87]  A. Debnath,et al.  Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors , 2004, The Lancet.

[88]  E. Ooi,et al.  In vitro inhibition of human influenza A virus replication by chloroquine , 2006, Virology Journal.

[89]  R. Razonable.  Antiviral Drugs for Viruses Other Than Human Immunodeficiency Virus , 2011, Mayo Clinic Proceedings.

[90]  L. Ren,et al.  Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. , 2020, JAMA.

[91]  Urso FORTE. Urso.  HIGHLIGHTS OF PRESCRIBING INFORMATION , 2007 .

[92]  G. Randall,et al.  Mechanism of action of ribavirin in the treatment of chronic hepatitis C. , 2007, Gastroenterology & hepatology.

[93]  A. Lefor,et al.  Favipiravir: A New Medication for the Ebola Virus Disease Pandemic , 2014, Disaster Medicine and Public Health Preparedness.

[94]  K. Kehn-Hall,et al.  Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce Venezuelan Equine Encephalitis Virus replication. , 2013, Antiviral research.

[95]  M. Lederman,et al.  Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence , 2019, PLoS pathogens.

[96]  E. Chorin,et al.  The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin , 2020, Nature Medicine.

[97]  W. Ma,et al.  Prolonged SARS-CoV-2 Viral Shedding in Patients with COVID-19 was Associated with Delayed Initiation of Arbidol Treatment: a retrospective cohort study , 2020, medRxiv.

[98]  Y. Guan,et al.  Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings , 2004, Thorax.

[99]  M. Müller,et al.  Challenges of Convalescent Plasma Infusion Therapy in Middle East Respiratory Coronavirus Infection: A Single Centre Experience , 2018, Antiviral therapy.

[100]  D. Raoult,et al.  Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial , 2020, International Journal of Antimicrobial Agents.

[101]  A. Cope,et al.  Associations between immune-suppressive and stimulating drugs and novel COVID-19—a systematic review of current evidence , 2020, Ecancermedicalscience.

[102]  A. Nishizono,et al.  Efficacy of Favipiravir (T-705) in Rabies Postexposure Prophylaxis , 2015, The Journal of infectious diseases.

[103]  G. Whittaker,et al.  Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites , 2009, Proceedings of the National Academy of Sciences.

[104]  B. Issac,et al.  Fingolimod induces neuronal-specific gene expression with potential neuroprotective outcomes in maturing neuronal progenitor cells exposed to HIV , 2017, Journal of NeuroVirology.

[105]  S. Bavari,et al.  The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus , 2019, iScience.

[106]  G. Herrler,et al.  SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor , 2020, Cell.

[107]  J. McCullers,et al.  Chloroquine is effective against influenza A virus in vitro but not in vivo , 2007, Influenza and other respiratory viruses.

[108]  A. Ciucci,et al.  Thiazolides, a New Class of Antiviral Agents Effective against Rotavirus Infection, Target Viral Morphogenesis, Inhibiting Viroplasm Formation , 2013, Journal of Virology.

[109]  Jianjun Gao,et al.  Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. , 2020, Bioscience trends.

[110]  M. Otto,et al.  Ribonucleoside Analogue That Blocks Replication of Bovine Viral Diarrhea and Hepatitis C Viruses in Culture , 2003, Antimicrobial Agents and Chemotherapy.

[111]  Kai Zhao,et al.  A pneumonia outbreak associated with a new coronavirus of probable bat origin , 2020, Nature.

[112]  D. Raoult,et al.  Teicoplanin: an alternative drug for the treatment of COVID-19? , 2020, International Journal of Antimicrobial Agents.

[113]  E. Adam,et al.  Severe COVID-19 infection in a patient with multiple sclerosis treated with fingolimod , 2020, Multiple Sclerosis and Related Disorders.

[114]  V. Wong,et al.  Severe acute respiratory syndrome: report of treatment and outcome after a major outbreak , 2004, Thorax.

[115]  Peter B. Madrid,et al.  Evaluation of Ebola Virus Inhibitors for Drug Repurposing. , 2015, ACS infectious diseases.

[116]  F. Romanelli,et al.  Chloroquine and hydroxychloroquine as inhibitors of human immunodeficiency virus (HIV-1) activity. , 2004, Current pharmaceutical design.

[117]  J. Peiris,et al.  The M, E, and N Structural Proteins of the Severe Acute Respiratory Syndrome Coronavirus Are Required for Efficient Assembly, Trafficking, and Release of Virus-Like Particles , 2008, Journal of Virology.

[118]  J. Angulo,et al.  Serum levels of interleukin-6 are linked to the severity of the disease caused by Andes Virus , 2017, PLoS neglected tropical diseases.

[119]  Bo Chen,et al.  Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial , 2020, medRxiv.

[120]  S. Polyak,et al.  The broad-spectrum antiviral drug arbidol inhibits foot-and-mouth disease virus genome replication. , 2019, The Journal of general virology.

[121]  J. Alam.  Buying Behavior Under Coronavirus Disease (COVID-19) Pandemic Situation: A Online Perspective Case in Bangladeshi Shoppers , 2020 .

[122]  H. Shirasawa,et al.  Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: Involvement of p38 MAPK and ERK , 2007, Antiviral Research.

[123]  Bo Zhong,et al.  RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak , 2020, Emerging microbes & infections.

[124]  H. Feldmann,et al.  Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge , 2019, Science Translational Medicine.

[125]  J. Zhao,et al.  Novel Nucleoside Analogue Fnc is Effective against Both Wild-Type and Lamivudine-Resistant HBV Clinical Isolates , 2012, Antiviral therapy.

[126]  R. Baric,et al.  Small-Molecule Antiviral β-d-N4-Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance , 2019, Journal of Virology.

[127]  R. Hilgenfeld.  From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design , 2014, The FEBS journal.

[128]  Xiaohu Zheng,et al.  Effective treatment of severe COVID-19 patients with tocilizumab , 2020, Proceedings of the National Academy of Sciences.

[129]  L. Dodd,et al.  Remdesivir for the Treatment of Covid-19 — Final Report , 2020, The New England journal of medicine.

[130]  Xuming Zhang,et al.  A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs , 2014, Antiviral Research.

[131]  M. Al-Jaghbeer,et al.  Tocilizumab for treatment of patients with severe COVID–19: A retrospective cohort study , 2020, EClinicalMedicine.

[132]  Q. Bassat,et al.  Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial. , 2020, JAMA network open.

[133]  Moon Y. F. Tay,et al.  Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin. , 2013, Antiviral research.

[134]  G. El-Azab,et al.  Two regimens of dexamethasone versus prednisolone for acute exacerbations in asthmatic Egyptian children , 2018, European journal of hospital pharmacy : science and practice.

[135]  A. Testori,et al.  Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[136]  Jianjun Gao,et al.  Discovering drugs to treat coronavirus disease 2019 (COVID-19). , 2020, Drug discoveries & therapeutics.

[137]  M. Otto,et al.  Inhibition of Severe Acute Respiratory Syndrome-Associated Coronavirus (SARSCoV) by Calpain Inhibitors and β-D-N4-Hydroxycytidine , 2004, Antiviral chemistry & chemotherapy.

[138]  B. Korba,et al.  Nitazoxanide, tizoxanide and other thiazolides are potent inhibitors of hepatitis B virus and hepatitis C virus replication. , 2008, Antiviral research.

[139]  Q. Ding,et al.  The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China , 2020, Journal of medical virology.

[140]  V. A. Maksimov,et al.  [Antiviral activity of arbidol and its derivatives against the pathogen of severe acute respiratory syndrome in the cell cultures]. , 2008, Voprosy virusologii.

[141]  A. White Jr..  Nitazoxanide: a new broad spectrum antiparasitic agent , 2004 .

[142]  S. Johnston,et al.  Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells , 2015, European Respiratory Journal.

[143]  Fumihiro Kato,et al.  Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells , 2020, Proceedings of the National Academy of Sciences.

[144]  I. Jelcic,et al.  Reactivation of herpesvirus under fingolimod: A case of severe herpes simplex encephalitis , 2015, Neurology.

[145]  M. Mitrović,et al.  Prophylactic and Therapeutic Activity , 2016 .

[146]  N. Ajami,et al.  Evidence of recombination in coronaviruses implicating pangolin origins of nCoV-2019 , 2020, bioRxiv.

[147]  J. Hardin,et al.  Outcomes of Hydroxychloroquine Usage in United States Veterans Hospitalized with COVID-19 , 2020, Med.

[148]  M. Biselli,et al.  In vitro effect of thymosin-alpha1 and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C. , 2001, Journal of viral hepatitis.

[149]  G. Cheng,et al.  Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice , 2017, EBioMedicine.

[150]  J. Rossignol.  Nitazoxanide: A first-in-class broad-spectrum antiviral agent , 2014, Antiviral Research.

[151]  Anthony S Fauci,et al.  Zika Virus in the Americas--Yet Another Arbovirus Threat. , 2016, The New England journal of medicine.

[152]  G. Cheng,et al.  Azithromycin Protects against Zika Virus Infection by Upregulating Virus-Induced Type I and III Interferon Responses , 2019, Antimicrobial Agents and Chemotherapy.

[153]  Y. Leo,et al.  Severe Acute Respiratory Syndrome (SARS) in Singapore: Clinical Features of Index Patient and Initial Contacts , 2003, Emerging infectious diseases.

[154]  M. Beer,et al.  Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import , 2016, Scientific Reports.

[155]  A. Cassone,et al.  Effects of chloroquine on viral infections: an old drug against today's diseases , 2003, The Lancet Infectious Diseases.

[156]  P. Horby,et al.  A novel coronavirus outbreak of global health concern , 2020, The Lancet.

[157]  T. Phan,et al.  Novel coronavirus: From discovery to clinical diagnostics , 2020, Infection, Genetics and Evolution.

[158]  B. He,et al.  Identification of Diverse Alphacoronaviruses and Genomic Characterization of a Novel Severe Acute Respiratory Syndrome-Like Coronavirus from Bats in China , 2014, Journal of Virology.

[159]  A. Goryaeva,et al.  Prediction of Mechanical Twinning in Magnesium Silicate Post-Perovskite , 2017, Scientific Reports.

[160]  Guo Chen,et al.  The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis , 2019, Critical Care.

[161]  Yi Guan,et al.  Lung pathology of fatal severe acute respiratory syndrome , 2003, The Lancet.

[162]  C. Rayner,et al.  Oseltamivir in seasonal, pandemic, and avian influenza: a comprehensive review of 10-years clinical experience , 2011, Advances in therapy.

[163]  Tatiana Baranovich,et al.  T-705 (Favipiravir) Induces Lethal Mutagenesis in Influenza A H1N1 Viruses In Vitro , 2013, Journal of Virology.

[164]  E. De Clercq,et al.  Inhibition of feline (FIPV) and human (SARS) coronavirus by semisynthetic derivatives of glycopeptide antibiotics , 2006, Antiviral Research.

[165]  Jason M Pogue,et al.  Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options , 2020, Open forum infectious diseases.

[166]  J. Farrar,et al.  A Randomized Controlled Trial of Chloroquine for the Treatment of Dengue in Vietnamese Adults , 2010, PLoS neglected tropical diseases.

[167]  Chen Wang,et al.  Influenza Inactive Virus Vaccine with the Fusion Peptide (rTα1- BP5) Enhances Protection Against Influenza Through Humoral and Cell-Mediated Immunity , 2016 .

[168]  M. Boeckh,et al.  Respiratory Viruses Other than Influenza Virus: Impact and Therapeutic Advances , 2008, Clinical Microbiology Reviews.

[169]  P L Jacobsen,et al.  An effective treatment. , 1987, CDA journal.

[170]  R. Bruno,et al.  Remdesivir for 5 or 10 Days in Patients with Severe Covid-19 , 2020, The New England journal of medicine.

[171]  Xilong Deng,et al.  Efficacy and Safety of Lopinavir/Ritonavir or Arbidol in Adult Patients with Mild/Moderate COVID-19: An Exploratory Randomized Controlled Trial , 2020, Med.

[172]  Arturo Casadevall,et al.  The convalescent sera option for containing COVID-19. , 2020, The Journal of clinical investigation.

[173]  S. Perlman,et al.  Coronaviruses: An Overview of Their Replication and Pathogenesis , 2015, Methods in molecular biology.

[174]  Robert Altenloh.  From a Novel , 1953 .

[175]  Zhiquan Hu,et al.  Effectiveness of Arbidol for COVID-19 Prevention in Health Professionals , 2020, Frontiers in Public Health.

[176]  M. Borca,et al.  The Role of Interleukin 6 During Viral Infections , 2019, Front. Microbiol..

[177]  D. Raoult,et al.  Azithromycin Inhibits the Replication of Zika Virus , 2018 .

[178]  C. Funk,et al.  A Snapshot of the Global Race for Vaccines Targeting SARS-CoV-2 and the COVID-19 Pandemic , 2020, Frontiers in Pharmacology.

[179]  I. Wilson,et al.  A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV , 2020, Science.

[180]  P. Maes,et al.  Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice , 2009, Antimicrobial Agents and Chemotherapy.

[181]  A. Randolph,et al.  Ribavirin for respiratory syncytial virus infection of the lower respiratory tract in infants and young children. , 2004, The Cochrane database of systematic reviews.

[182]  A. Arvey,et al.  GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses , 2017, Scientific Reports.

[183]  B. Gazzard,et al.  Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial. , 2012, JAMA.

[184]  Makoto Takeda,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 , 2016, Antimicrobial Agents and Chemotherapy.

[185]  E. Frolova,et al.  β-d-N4-Hydroxycytidine Is a Potent Anti-alphavirus Compound That Induces a High Level of Mutations in the Viral Genome , 2017, Journal of Virology.

[186]  Dong Liu,et al.  Tocilizumab treatment in COVID‐19: A single center experience , 2020, Journal of medical virology.

[187]  Zhìhóng Hú,et al.  The anti-influenza virus drug, arbidol is an efficient inhibitor of SARS-CoV-2 in vitro , 2020, Cell Discovery.

[188]  V. Egorov,et al.  Triazavirine supramolecular complexes as modifiers of the peptide oligomeric structure , 2017, bioRxiv.

[189]  S. Polyak,et al.  Arbidol as a broad-spectrum antiviral: An update , 2014, Antiviral Research.

[190]  S. W. Long,et al.  Treatment of Coronavirus Disease 2019 (COVID-19) Patients with Convalescent Plasma , 2020, The American Journal of Pathology.

[191]  A. Tahghighi,et al.  Introducing New Antimalarial Analogues of Chloroquine and Amodiaquine: A Narrative Review , 2017, Iranian journal of medical sciences.

[192]  Xiaotao Lu,et al.  Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease , 2018, mBio.

[193]  N. Borg,et al.  The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer. , 2020, Antiviral research.

[194]  Erwan L'Her,et al.  Compassionate Use of Remdesivir for Patients with Severe Covid-19 , 2020, The New England journal of medicine.

[195]  H. Feldmann,et al.  Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin , 2013, Scientific Reports.

[196]  G. Redelman-Sidi,et al.  ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors). , 2018, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[197]  Q. Wang,et al.  FNC, a novel nucleoside analogue inhibits cell proliferation and tumor growth in a variety of human cancer cells. , 2011, Biochemical pharmacology.

[198]  R. Hilgenfeld,et al.  Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors , 2020, Science.

[199]  Martin Stahl,et al.  Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 , 2020, Cell.

[200]  R. Nagatomi,et al.  The serine protease inhibitor camostat inhibits influenza virus replication and cytokine production in primary cultures of human tracheal epithelial cells , 2015, Pulmonary Pharmacology & Therapeutics.

[201]  Thi Huyen Tram Nguyen,et al.  Antiviral efficacy of favipiravir against Ebola virus: A translational study in cynomolgus macaques , 2018, PLoS medicine.

[202]  Rajaa Al-Raddadi,et al.  Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome , 2017, American journal of respiratory and critical care medicine.

[203]  K. Subbarao,et al.  pH-Dependent Entry of Severe Acute Respiratory Syndrome Coronavirus Is Mediated by the Spike Glycoprotein and Enhanced by Dendritic Cell Transfer through DC-SIGN , 2004, Journal of Virology.

[204]  Jing Wu,et al.  Inflammation suppression by dexamethasone via inhibition of CD147-mediated NF-κB pathway in collagen-induced arthritis rats , 2020, Molecular and Cellular Biochemistry.

[205]  Qibo Zhang,et al.  MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile , 2018, Cytokine.

[206]  Y. Guan,et al.  In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds , 2004, Journal of Clinical Virology.

[207]  Z. Memish,et al.  Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study , 2014, International Journal of Infectious Diseases.

[208]  J. Rossignol.  Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus , 2016, Journal of Infection and Public Health.

[209]  R. Holubkov,et al.  A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. , 2007, The New England journal of medicine.

[210]  Hongzhou Lu,et al.  Efficacies of lopinavir/ritonavir and abidol in the treatment of novel coronavirus pneumonia , 2020 .

[211]  Muhammad Yasir,et al.  Corticosteroid Adverse Effects , 2019 .

[212]  Lidia Ruiz,et al.  Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[213]  A. Faizul.  Targeting SARS-CoV-2 Main Protease by Teicoplanin: A Mechanistic Insight by in Silico Studies , 2020 .

[214]  C. Coronelli,et al.  Teichomycins, new antibiotics from Actinoplanes teichomyceticus nov. sp. IV. Separation and characterization of the components of teichomycin (teicoplanin). , 1984, The Journal of antibiotics.

[215]  A. Billich.  Thymosin alpha1. SciClone Pharmaceuticals. , 2002, Current opinion in investigational drugs.

[216]  N. Tordo,et al.  Arbidol (Umifenovir): A Broad-Spectrum Antiviral Drug That Inhibits Medically Important Arthropod-Borne Flaviviruses , 2018, Viruses.

[217]  Guiming Li,et al.  Teicoplanin inhibits Ebola pseudovirus infection in cell culture , 2015, Antiviral Research.

[218]  H. Kung,et al.  Inhibition of human immunodeficiency virus infectivity by chloroquine. , 1990, AIDS research and human retroviruses.

[219]  A. Petherick.  Developing antibody tests for SARS-CoV-2 , 2020, The Lancet.

[220]  D. Raoult,et al.  In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect , 2020, Microbial Pathogenesis.

[221]  Ralph S. Baric,et al.  Severe Acute Respiratory Syndrome Coronavirus ORF6 Antagonizes STAT1 Function by Sequestering Nuclear Import Factors on the Rough Endoplasmic Reticulum/Golgi Membrane , 2007, Journal of Virology.

[222]  Zhengzhao Liu,et al.  Immunoregulation of Thymosin α 1 Treatment of Cytomegalovirus Infection Accompanied With Acute Respiratory Distress Syndrome After Renal Transplantation , 2007 .

[223]  J. Toyota,et al.  The efficacy and safety of thymosin alpha‐1 in Japanese patients with chronic hepatitis B; results from a randomized clinical trial , 2005, Journal of viral hepatitis.

[224]  A. deLemos,et al.  Changing the face of hepatitis C management – the design and development of sofosbuvir , 2015, Drug design, development and therapy.

[225]  Shibo Jiang,et al.  The spike protein of SARS-CoV — a target for vaccine and therapeutic development , 2009, Nature Reviews Microbiology.

[226]  E. De Clercq.  Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. , 2009, International journal of antimicrobial agents.

[227]  M. Massari,et al.  Tocilizumab in patients with severe COVID-19: a retrospective cohort study , 2020, The Lancet Rheumatology.

[228]  A. Elfiky,et al.  Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study , 2020, Life Sciences.

[229]  Christian Drosten,et al.  The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated by TMPRSS2, and Is Targeted by Neutralizing Antibodies , 2013, Journal of Virology.

[230]  J. Stone,et al.  Trial of Tocilizumab in Giant‐Cell Arteritis , 2017, The New England journal of medicine.

[231]  Joy Y. Feng,et al.  Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir , 2019, Viruses.

[232]  H. Feldmann,et al.  Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection , 2020, Proceedings of the National Academy of Sciences.

[233]  Charlotte Harrison,et al.  Coronavirus puts drug repurposing on the fast track , 2020, Nature Biotechnology.

[234]  A. Strongin,et al.  Repurposing of the anti-malaria drug chloroquine for Zika Virus treatment and prophylaxis , 2017, Scientific Reports.

[235]  N. Nomura,et al.  Mechanism of Action of T-705 Ribosyl Triphosphate against Influenza Virus RNA Polymerase , 2013, Antimicrobial Agents and Chemotherapy.

[236]  William A. Lee,et al.  Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys , 2016, Nature.

[237]  T. Bestebroer,et al.  Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture , 2014, Antimicrobial Agents and Chemotherapy.

[238]  R. Plemper,et al.  Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia , 2019, Science Translational Medicine.

[239]  Nicole M. Bouvier,et al.  Convalescent plasma treatment of severe COVID-19: A matched control study , 2020, medRxiv.

[240]  A. Gamarnik,et al.  An Analogue of the Antibiotic Teicoplanin Prevents Flavivirus Entry In Vitro , 2012, PloS one.

[241]  Wu Zhong,et al.  The anti-influenza virus drug, arbidol is an efficient inhibitor of SARS-CoV-2 in vitro , 2020, Cell Discovery.

[242]  Emily G McDonald,et al.  A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 , 2020, The New England journal of medicine.

[243]  R. Crystal,et al.  Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema. , 2000, American journal of respiratory cell and molecular biology.

[244]  Qianyun Liu,et al.  Emerging coronaviruses: Genome structure, replication, and pathogenesis , 2020, Journal of medical virology.

[245]  Xuhui Huang,et al.  Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro , 2020, Antiviral Research.

[246]  B. Lim,et al.  Inhibition of SARS Coronavirus Infection In Vitro with Clinically Approved Antiviral Drugs , 2004, Emerging infectious diseases.

[247]  Jianchao Wei,et al.  Nitazoxanide inhibits the replication of Japanese encephalitis virus in cultured cells and in a mouse model , 2014, Virology Journal.

[248]  T. Pan,et al.  Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) , 2016, The Journal of Biological Chemistry.

[249]  F. Parenti,et al.  Teichomycins, new antibiotics from Actinoplanes teichomyceticus Nov. Sp. I. Description of the producer strain, fermentation studies and biological properties. , 1978, The Journal of antibiotics.

[250]  E. Holmes,et al.  Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding , 2020, The Lancet.

[251]  Wenjing Guo,et al.  Chloroquine inhibits endosomal viral RNA release and autophagy-dependent viral replication and effectively prevents maternal to fetal transmission of Zika virus. , 2019, Antiviral research.

[252]  Xiaotao Lu,et al.  An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice , 2020, Science Translational Medicine.

[253]  Wu Zhong,et al.  Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro , 2020, Cell Research.

[254]  Michael Proschan,et al.  A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. , 2019, The New England journal of medicine.

[255]  Ting Ni,et al.  A bioenergetic shift is required for spermatogonial differentiation , 2020, Cell Discovery.

[256]  A. Goldstein,et al.  Thymosins: structure, function and therapeutic applications. , 1984, Thymus.

[257]  J. Tao,et al.  Emergency management for preventing and controlling nosocomial infection of the 2019 novel coronavirus: implications for the dermatology department , 2020, The British journal of dermatology.

[258]  Xinglong Wang,et al.  Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo , 2018, Antiviral research.

[259]  L. Naesens,et al.  Semisynthetic teicoplanin derivatives as new influenza virus binding inhibitors: synthesis and antiviral studies. , 2014, Bioorganic & medicinal chemistry letters.

[260]  S. Anzick,et al.  Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2 , 2020, Nature.

[261]  Pavel V Baranov,et al.  Programmed ribosomal frameshifting in decoding the SARS-CoV genome , 2005, Virology.

[262]  Wu Zhong,et al.  Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study , 2020, Engineering.

[263]  N. Seidah,et al.  Chloroquine is a potent inhibitor of SARS coronavirus infection and spread , 2005, Virology Journal.

[264]  D. Jans,et al.  The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro , 2020, Antiviral Research.

[265]  T. Pan,et al.  Teicoplanin potently blocks the cell entry of 2019-nCoV , 2020, medRxiv.

[266]  G. Dangas,et al.  Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019 , 2020, JAMA network open.

[267]  R. Baric,et al.  Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV , 2020, Nature Communications.

[268]  S. Ravindran,et al.  A pilot study of the safety and efficacy of thymosin α1 in augmenting immune reconstitution in HIV‐infected patients with low CD4 counts taking highly active antiretroviral therapy , 2003, Clinical and experimental immunology.

[269]  Zhenhong Hu,et al.  Thymosin alpha 1 (Tα1) reduces the mortality of severe COVID-19 by restoration of lymphocytopenia and reversion of exhausted T cells , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[270]  Patrick W. Johnson,et al.  Early safety indicators of COVID-19 convalescent plasma in 5,000 patients. , 2020, The Journal of clinical investigation.

[271]  Md Abdul Alim Al-Bari,et al.  Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases , 2015, The Journal of antimicrobial chemotherapy.

[272]  Yuan Wei,et al.  A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19 , 2020, The New England journal of medicine.

[273]  R. Plemper,et al.  Orally Efficacious Broad-Spectrum Ribonucleoside Analog Inhibitor of Influenza and Respiratory Syncytial Viruses , 2018, Antimicrobial Agents and Chemotherapy.

[274]  M. Matsuoka,et al.  Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. , 2015, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[275]  D. Ye,et al.  Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence , 2020, International Journal of Antimicrobial Agents.

[276]  Wei Zhang,et al.  Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. , 2020, Bioscience trends.

[277]  Hannah R. Meredith,et al.  The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application , 2020, Annals of Internal Medicine.

[278]  A. Millar,et al.  Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): paradox or paradigm? , 2006, Thorax.

[279]  P. Zhao,et al.  Japanese Encephalitis Virus Enters Rat Neuroblastoma Cells via a pH-Dependent, Dynamin and Caveola-Mediated Endocytosis Pathway , 2012, Journal of Virology.

[280]  Wu Zhong,et al.  Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro , 2020, Cell Discovery.

[281]  A. Kolykhalov,et al.  The prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model of intranasal venezuelan equine encephalitis virus infection. , 2019, Antiviral research.

[282]  E. Roilides,et al.  H1N1 influenza A infection. , 2009, Hippokratia.

[283]  A. Pekosz,et al.  Intracellular Localization of the Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein: Absence of Nucleolar Accumulation during Infection and after Expression as a Recombinant Protein in Vero Cells , 2005, Journal of Virology.

[284]  Rui-guang Zhang,et al.  Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[285]  H. Kerschner,et al.  Teicoplanin therapy leading to a significant decrease in viral load in a patient with chronic hepatitis C , 2012, The Journal of antimicrobial chemotherapy.

[286]  Kwok-Hung Chan,et al.  Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial , 2020, The Lancet.

[287]  Alicia M. Hanson,et al.  Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug. , 2012, The Journal of antimicrobial chemotherapy.

[288]  Gideon Koren,et al.  Ribavirin in the treatment of SARS: A new trick for an old drug? , 2003, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[289]  Arthur S Slutsky,et al.  Identification of severe acute respiratory syndrome in Canada. , 2003, The New England journal of medicine.

[290]  Qiurong Ruan,et al.  Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China , 2020, Intensive Care Medicine.

[291]  D. Barnard,et al.  Evaluation of Immunomodulators, Interferons and Known in Vitro SARS-CoV Inhibitors for Inhibition of SARS-Cov Replication in BALB/c Mice , 2006, Antiviral chemistry & chemotherapy.

[292]  D. Harrich,et al.  Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus , 2012, The Biochemical journal.

[293]  R. Ghildyal,et al.  Nucleocytoplasmic transport of nucleocapsid proteins of enveloped RNA viruses , 2015, Front. Microbiol..

[294]  G. Hripcsak,et al.  Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19 , 2020, The New England journal of medicine.

[295]  S. Ōmura,et al.  Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(H1N1)pdm09 virus infection by interfering with virus internalization process , 2019, The Journal of Antibiotics.

[296]  N. Dalbeth,et al.  Mechanism of action of colchicine in the treatment of gout. , 2014, Clinical therapeutics.

[297]  P. Chan,et al.  Use of convalescent plasma therapy in SARS patients in Hong Kong , 2004, European Journal of Clinical Microbiology and Infectious Diseases.

[298]  Jari Saramäki,et al.  Detection of timescales in evolving complex systems , 2016, Scientific Reports.

[299]  X. Mariette,et al.  ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors). , 2018, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.