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Review

Experimental Antiviral Therapeutic Studies for Human Rhinovirus Infections

ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 645-659 | Published online: 09 Jul 2021

References

  • Price WH. The isolation of a new virus associated with respiratory clinical disease in humans. Proc Natl Acad Sci USA. 1956;42(12):892–896. doi:10.1073/pnas.42.12.892
  • Johnston SL, Pattemore PK, Sanderson G, et al. Community study of role of viral infections in exacerbations of asthma in 9–11 year old children. BMJ. 1995;310(6989):1225–1229. doi:10.1136/bmj.310.6989.1225
  • Seemungal T, Harper-Owen R, Bhowmik A, et al. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;164(9):1618–1623. doi:10.1164/ajrccm.164.9.2105011
  • Aponte FE, Taboada B, Espinoza MA, et al. Rhinovirus is an important pathogen in upper and lower respiratory tract infections in Mexican children. Virol J. 2015;12:31. doi:10.1186/s12985-015-0262-z
  • Redlberger-Fritz M, Kundi M, Aberle SW, Puchhammer-Stöckl E. Significant impact of nationwide SARS-CoV-2 lockdown measures on the circulation of other respiratory virus infections in Austria. J Clin Virol. 2021;137:104795. doi:10.1016/j.jcv.2021.104795
  • Weston S, Frieman MB. Respiratory Viruses. Reference Module in Biomedical Sciences. Elsevier; 2018.
  • Cafferkey J, Coultas JA, Mallia P. Human rhinovirus infection and COPD: role in exacerbations and potential for therapeutic targets. Expert Rev Respir Med. 2020;14(8):777–789. doi:10.1080/17476348.2020.1764354
  • Jacobs SE, Lamson DM, St George K, Walsh TJ. Human rhinoviruses. Clin Microbiol Rev. 2013;26(1):135–162.
  • McIntyre CL, Knowles NJ, Simmonds P. Proposals for the classification of human rhinovirus species A, B and C into genotypically assigned types. J Gen Virol. 2013;94(Pt 8):1791–1806. doi:10.1099/vir.0.053686-0
  • Lamson D, Renwick N, Kapoor V, et al. MassTag polymerase-chain-reaction detection of respiratory pathogens, including a new rhinovirus genotype, that caused influenza-like illness in New York State during 2004–2005. J Infect Dis. 2006;194(10):1398–1402. doi:10.1086/508551
  • Lau SKP, Yip CCY, Woo PCY, Yuen KY. Human rhinovirus C: a newly discovered human rhinovirus species. Emerg Health Threats J. 2010;4(3):e2.
  • Palmenberg AC, Rathe JA, Liggett SB. Analysis of the complete genome sequences of human rhinovirus. J Allergy Clin Immunol. 2010;125(6):1190–1199. doi:10.1016/j.jaci.2010.04.010
  • Spickler C, Lippens J, Laberge M-K, et al. Phosphatidylinositol 4-kinase III beta is essential for replication of human rhinovirus and its inhibition causes a lethal phenotype in vivo. Antimicrob Agents Chemother. 2013;57(7):3358–3368. doi:10.1128/AAC.00303-13
  • Ambros V, Baltimore D. Protein is linked to the 5’ end of poliovirus RNA by a phosphodiester linkage to tyrosine. J Biol Chem. 1978;253(15):5263–5266. doi:10.1016/S0021-9258(17)30361-7
  • Sun D, Chen S, Cheng A, Wang M. Roles of the picornaviral 3C proteinase in the viral life cycle and host cells. Viruses. 2016;8(3):82. doi:10.3390/v8030082
  • Appleby TC, Luecke H, Shim JH, et al. Crystal structure of complete rhinovirus RNA polymerase suggests front loading of protein primer. J Virol. 2005;79(1):277–288. doi:10.1128/JVI.79.1.277-288.2005
  • Colonno RJ, Condra JH, Mizutani S, Callahan PL, Davies ME, Murcko MA. Evidence for the direct involvement of the rhinovirus canyon in receptor binding. Proc Natl Acad Sci USA. 1988;85(15):5449–5453. doi:10.1073/pnas.85.15.5449
  • Bella J, Rossmann MG. ICAM-1 receptors and cold viruses. Pharm Acta Helv. 2000;74(2–3):291–297. doi:10.1016/S0031-6865(99)00056-4
  • Liu Y, Hill MG, Klose T, et al. Atomic structure of a rhinovirus C, a virus species linked to severe childhood asthma. Proc Natl Acad Sci USA. 2016;113(32):8997–9002. doi:10.1073/pnas.1606595113
  • Hofer F, Gruenberger M, Kowalski H, et al. Members of the low density lipoprotein receptor family mediate cell entry of a minor-group common cold virus. Proc Natl Acad Sci USA. 1994;91(5):1839–1842. doi:10.1073/pnas.91.5.1839
  • Bochkov YA, Palmenberg AC, Lee WM, et al. Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C. Nat Med. 2011;17(5):627–632. doi:10.1038/nm.2358
  • Everman JL, Sajuthi S, Saef B, et al. Functional genomics of CDHR3 confirms its role in HRV-C infection and childhood asthma exacerbations. J Allergy Clin Immunol. 2019;144(4):962–971. doi:10.1016/j.jaci.2019.01.052
  • Laza-Stanca V, Stanciu LA, Message SD, Edwards MR, Gern JE, Johnston SL. Rhinovirus replication in human macrophages induces NF-kappaB-dependent tumor necrosis factor alpha production. J Virol. 2006;80(16):8248–8258. doi:10.1128/JVI.00162-06
  • Slater L, Bartlett NW, Haas JJ, et al. Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium. PLoS Pathog. 2010;6(11):e1001178. doi:10.1371/journal.ppat.1001178
  • Fensterl V, Chattopadhyay S, Sen GC. No love lost between viruses and interferons. Annu Rev Virol. 2015;2(1):549–572. doi:10.1146/annurev-virology-100114-055249
  • Kennedy JL, Turner RB, Braciale T, Heymann PW, Borish L. Pathogenesis of rhinovirus infection. Curr Opin Virol. 2012;2(3):287–293. doi:10.1016/j.coviro.2012.03.008
  • Kaul P, Biagioli MC, Singh I, Turner RB. Rhinovirus-induced oxidative stress and interleukin-8 elaboration involves p47-phox but is independent of attachment to intercellular adhesion molecule-1 and viral replication. J Infect Dis. 2000;181(6):1885–1890. doi:10.1086/315504
  • Mallia P, Message SD, Kebadze T, Parker HL, Kon OM, Johnston SL. An experimental model of rhinovirus induced chronic obstructive pulmonary disease exacerbations: a pilot study. Respir Res. 2006;7(1):116. doi:10.1186/1465-9921-7-116
  • Mallia P, Message SD, Gielen V, et al. Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation. Am J Respir Crit Care Med. 2011;183(6):734–742. doi:10.1164/rccm.201006-0833OC
  • Footitt J, Mallia P, Durham AL, et al. Oxidative and nitrosative stress and histone deacetylase-2 activity in exacerbations of COPD. Chest. 2016;149(1):62–73. doi:10.1378/chest.14-2637
  • Hilzendeger C, da Silva J, Henket M, et al. Reduced sputum expression of interferon-stimulated genes in severe COPD. Int J Chron Obstruct Pulmon Dis. 2016;Volume 11(11):1485–1494. doi:10.2147/COPD.S105948
  • García-Valero J, Olloquequi J, Montes JF, et al. Deficient pulmonary IFN-β expression in COPD patients. PLoS One. 2019;14(6):e0217803. doi:10.1371/journal.pone.0217803
  • Baines KJ, Hsu ACY, Tooze M, Gunawardhana LP, Gibson PG, Wark PAB. Novel immune genes associated with excessive inflammatory and antiviral responses to rhinovirus in COPD. Respir Res. 2013;14:15. doi:10.1186/1465-9921-14-15
  • Singanayagam A, Loo SL, Calderazzo M, et al. Antiviral immunity is impaired in COPD patients with frequent exacerbations. Am J Physiol Lung Cell Mol Physiol. 2019;317(6):L893–L903. doi:10.1152/ajplung.00253.2019
  • Wark PAB, Johnston SL, Bucchieri F, et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med. 2005;201(6):937–947. doi:10.1084/jem.20041901
  • Contoli M, Message SD, Laza-Stanca V, et al. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med. 2006;12(9):1023–1026. doi:10.1038/nm1462
  • Edwards MR, Regamey N, Vareille M, et al. Impaired innate interferon induction in severe therapy resistant atopic asthmatic children. Mucosal Immunol. 2013;6(4):797–806. doi:10.1038/mi.2012.118
  • Miller EK, Hernandez JZ, Wimmenauer V, et al. A mechanistic role for type III IFN-λ1 in asthma exacerbations mediated by human rhinoviruses. Am J Respir Crit Care Med. 2012;185(5):508–516. doi:10.1164/rccm.201108-1462OC
  • Hansel TT, Tunstall T, Trujillo-Torralbo M-B, et al. A comprehensive evaluation of nasal and bronchial cytokines and chemokines following experimental rhinovirus infection in allergic asthma: increased interferons (IFN-γ and IFN-λ) and type 2 inflammation (IL-5 and IL-13). EBioMedicine. 2017;19:128–138. doi:10.1016/j.ebiom.2017.03.033
  • Kennedy JL, Shaker M, McMeen V, et al. Comparison of viral load in individuals with and without asthma during infections with rhinovirus. Am J Respir Crit Care Med. 2014;189(5):532–539. doi:10.1164/rccm.201310-1767OC
  • Farne HA, Johnston SL. Immune mechanisms of respiratory viral infections in asthma. Curr Opin Immunol. 2017;48:31–37. doi:10.1016/j.coi.2017.07.017
  • Jackson DJ, Makrinioti H, Rana BMJ, et al. IL-33-dependent type 2 inflammation during rhinovirus-induced asthma exacerbations in vivo. Am J Respir Crit Care Med. 2014;190(12):1373–1382. doi:10.1164/rccm.201406-1039OC
  • Tyrrell DA. A view from the common cold unit. Antiviral Res. 1992;18(2):105–125. doi:10.1016/0166-3542(92)90032-Z
  • Andrewes CH. The common cold. Br Med Bull. 1953;9(3):206–207. doi:10.1093/oxfordjournals.bmb.a074357
  • Rosenbaum JR, Sepkowitz KA. Infectious disease experimentation involving human volunteers. Clin Infect Dis. 2002;34(7):963–971. doi:10.1086/339328
  • Sperber SJ, Hunger SB, Schwartz B, Pestka S. Anti-rhinoviral activity of recombinant and hybrid species of interferon alpha. Antiviral Res. 1993;22(2–3):121–129. doi:10.1016/0166-3542(93)90090-6
  • Al-Nakib W, Higgins PG, Barrow I, Tyrrell DA, Lenox-Smith I, Ishitsuka H. Intranasal chalcone, Ro 09-0410, as prophylaxis against rhinovirus infection in human volunteers. J Antimicrob Chemother. 1987;20(6):887–892. doi:10.1093/jac/20.6.887
  • al-Nakib W, Higgins PG, Barrow GI, et al. Suppression of colds in human volunteers challenged with rhinovirus by a new synthetic drug (R61837). Antimicrob Agents Chemother. 1989;33(4):522–525. doi:10.1128/AAC.33.4.522
  • Lemanske RF, Dick EC, Swenson CA, Vrtis RF, Busse WW. Rhinovirus upper respiratory infection increases airway hyperreactivity and late asthmatic reactions. J Clin Invest. 1989;83(1):1–10. doi:10.1172/JCI113843
  • Bardin PG, Fraenkel DJ, Sanderson G, et al. Amplified rhinovirus colds in atopic subjects. Clin Exp Allergy. 1994;24(5):457–464. doi:10.1111/j.1365-2222.1994.tb00934.x
  • de Gouw HW, Grünberg K, Schot R, Kroes AC, Dick EC, Sterk PJ. Relationship between exhaled nitric oxide and airway hyperresponsiveness following experimental rhinovirus infection in asthmatic subjects. Eur Respir J. 1998;11(1):126–132. doi:10.1183/09031936.98.11010126
  • Heymann PW, Tae PM, Woodfolk JA, et al. Understanding the asthmatic response to an experimental rhinovirus infection: exploring the effects of blocking IgE. J Allergy Clin Immunol. 2020;146(3):545–554. doi:10.1016/j.jaci.2020.01.035
  • Zambrano JC, Carper HT, Rakes GP, et al. Experimental rhinovirus challenges in adults with mild asthma: response to infection in relation to IgE. J Allergy Clin Immunol. 2003;111(5):1008–1016. doi:10.1067/mai.2003.1396
  • Togo Y, Schwartz AR, Hornick RB. Antiviral effect of 3, 4-dihydro-1-isoquinolineacetamide hydrochloride in experimental human rhinovirus infection. Antimicrob Agents Chemother. 1973;4(6):612–616. doi:10.1128/AAC.4.6.612
  • Turner RB, Riker DK, Gangemi JD. Ineffectiveness of echinacea for prevention of experimental rhinovirus colds. Antimicrob Agents Chemother. 2000;44(6):1708–1709. doi:10.1128/AAC.44.6.1708-1709.2000
  • Gaffey MJ, Gwaltney JM, Sastre A, Dressler WE, Sorrentino JV, Hayden FG. Intranasally and orally administered antihistamine treatment of experimental rhinovirus colds. Am Rev Respir Dis. 1987;136(3):556–560. doi:10.1164/ajrccm/136.3.556
  • Winther B, Buchert D, Turner RB, Hendley JO, Tschaikin M. Decreased rhinovirus shedding after intranasal oxymetazoline application in adults with induced colds compared with intranasal saline. Am J Rhinol Allergy. 2010;24(5):374–377. doi:10.2500/ajra.2010.24.3491
  • Togo Y, Durr FE, Laurenzana DA. Clinical evaluation of prophylactic intranasal 1-phenyl-3-(4-phenyl-2-thiazolyl) guanidine (CL 88,277) medication against rhinovirus 44 challenge. Med Microbiol Immunol. 1977;163(1):37–44. doi:10.1007/BF02126707
  • Sperber SJ, Sorrentino JV, Riker DK, Hayden FG. Evaluation of an alpha agonist alone and in combination with a nonsteroidal antiinflammatory agent in the treatment of experimental rhinovirus colds. Bull N Y Acad Med. 1989;65(1):145–160.
  • Higgins PG, al-Nakib W, Barrow GI, Tyrrell DA. Recombinant human interferon-gamma as prophylaxis against rhinovirus colds in volunteers. J Interferon Res. 1988;8(5):591–596. doi:10.1089/jir.1988.8.591
  • Al-Nakib W, Higgins PG, Barrow I, Batstone G, Tyrrell DA. Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges. J Antimicrob Chemother. 1987;20(6):893–901. doi:10.1093/jac/20.6.893
  • The Academy of Medical Sciences. Controlled human infection model studies: summary of a workshop held on 6 February 2018. The Academy of Medical Sciences [Internet]. 2018 [cited December 15, 2020]; Available from: https://acmedsci.ac.uk/file-download/55062331. Accessed June 4, 2021.
  • Johnston SL. Experimental models of rhinovirus-induced exacerbations of asthma. Am J Respir Crit Care Med. 2003;168(10):1145–1146. doi:10.1164/rccm.2309004
  • Girkin J, Maltby S, Singanayagam A, Bartlett N, Mallia P. In vivo experimental models of infection and disease. In: Rhinovirus Infections. Elsevier; 2019:195–238.
  • Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390(10095):659–668. doi:10.1016/S0140-6736(17)31281-3
  • Johnston SL, Szigeti M, Cross M, et al. Azithromycin for acute exacerbations of asthma: the AZALEA randomized clinical trial. JAMA Intern Med. 2016;176(11):1630–1637. doi:10.1001/jamainternmed.2016.5664
  • Djukanović R, Harrison T, Johnston SL, et al. The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. A randomized trial. Am J Respir Crit Care Med. 2014;190(2):145–154. doi:10.1164/rccm.201312-2235OC
  • Hayden FG, Andries K, Janssen PA. Safety and efficacy of intranasal pirodavir (R77975) in experimental rhinovirus infection. Antimicrob Agents Chemother. 1992;36(4):727–732. doi:10.1128/AAC.36.4.727
  • Hayden FG, Hipskind GJ, Woerner DH, et al. Intranasal pirodavir (R77,975) treatment of rhinovirus colds. Antimicrob Agents Chemother. 1995;39(2):290–294. doi:10.1128/AAC.39.2.290
  • Hayden FG, Herrington DT, Coats TL, et al. Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of 2 double-blind, randomized, placebo-controlled trials. Clin Infect Dis. 2003;36(12):1523–1532. doi:10.1086/375069
  • Smee DF, Evans WJ, Nicolaou KC, Tarbet EB, Day CW. Susceptibilities of enterovirus D68, enterovirus 71, and rhinovirus 87 strains to various antiviral compounds. Antiviral Res. 2016;131:61–65. doi:10.1016/j.antiviral.2016.04.003
  • Andersen DO, Murray BK, Robins RK, North JA. In vitro antiviral activity of ribavirin against picornaviruses. Antivir Chem Chemother. 1992;3(6):361–370. doi:10.1177/095632029200300606
  • Ruuskanen O, Waris M, Kainulainen L. Treatment of persistent rhinovirus infection with pegylated interferon α2a and ribavirin in patients with hypogammaglobulinemia. Clin Infect Dis. 2014;58(12):1784–1786. doi:10.1093/cid/ciu169
  • Turner RB, Wecker MT, Pohl G, et al. Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection: a randomized clinical trial. JAMA. 1999;281(19):1797–1804. doi:10.1001/jama.281.19.1797
  • Vapendavir significantly improves upper respiratory symptoms of naturally acquired rhinovirus infection in asthmatic adults: results of a Phase 2 clinical trial | European Respiratory Society [Internet]. [ cited May 15, 2021]. Available from: https://erj.ersjournals.com/content/42/Suppl_57/1493. Accessed June 4, 2021.
  • Jolliffe DA, Camargo CA, Sluyter JD, et al. Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021;9(5):276–292. doi:10.1016/S2213-8587(21)00051-6
  • Beaucourt S, Vignuzzi M. Ribavirin: a drug active against many viruses with multiple effects on virus replication and propagation. Molecular basis of ribavirin resistance. Curr Opin Virol. 2014;8:10–15. doi:10.1016/j.coviro.2014.04.011
  • Ledford RM, Patel NR, Demenczuk TM, et al. VP1 sequencing of all human rhinovirus serotypes: insights into genus phylogeny and susceptibility to antiviral capsid-binding compounds. J Virol. 2004;78(7):3663–3674. doi:10.1128/JVI.78.7.3663-3674.2004
  • Basta HA, Ashraf S, Sgro JY, Bochkov YA, Gern JE, Palmenberg AC. Modeling of the human rhinovirus C capsid suggests possible causes for antiviral drug resistance. Virology. 2014;448:82–90. doi:10.1016/j.virol.2013.10.004
  • Schwitzer G. How the media left the evidence out in the cold. BMJ. 2003;326(7403):1403–1404. doi:10.1136/bmj.326.7403.1403
  • ClinicalTrials.gov. Effects of pleconaril nasal spray on common cold symptoms and asthma exacerbations following rhinovirus exposure (study P04295). ClinicalTrials.gov: ClinicalTrials.gov; 2015.
  • Andries K, Dewindt B, Snoeks J, et al. In vitro activity of pirodavir (R 77975), a substituted phenoxy-pyridazinamine with broad-spectrum antipicornaviral activity. Antimicrob Agents Chemother. 1992;36(1):100–107. doi:10.1128/AAC.36.1.100
  • Biota Pharmaceuticals. A phase 2 study of vapendavir in asthmatic adults with symptomatic human rhinovirus infection (SPIRITUS) [Internet]. ClinicalTrials.gov, editor. ClinicalTrials.gov: ClinicalTrials.gov; 2018 [cited February 28, 2021]. Available from: https://clinicaltrials.gov/ct2/show/NCT02367313. Accessed June 4, 2021.
  • Wald J, Pasin M, Richter M, et al. Cryo-EM structure of pleconaril-resistant rhinovirus-B5 complexed to the antiviral OBR-5-340 reveals unexpected binding site. Proc Natl Acad Sci USA. 2019;116(38):19109–19115. doi:10.1073/pnas.1904732116
  • Makarov VA, Braun H, Richter M, et al. Pyrazolopyrimidines: potent inhibitors targeting the capsid of rhino- and enteroviruses. Chem Med Chem. 2015;10(10):1629–1634. doi:10.1002/cmdc.201500304
  • Lacroix C, Laconi S, Angius F, et al. In vitro characterisation of a pleconaril/pirodavir-like compound with potent activity against rhinoviruses. Virol J. 2015;12:106. doi:10.1186/s12985-015-0330-4
  • Dragovich PS, Prins TJ, Zhou R, et al. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 4. Incorporation of P1 lactam moieties as L-glutamine replacements. J Med Chem. 1999;42(7):1213–1224. doi:10.1021/jm9805384
  • Patick AK, Binford SL, Brothers MA, et al. In vitro antiviral activity of AG7088, a potent inhibitor of human rhinovirus 3C protease. Antimicrob Agents Chemother. 1999;43(10):2444–2450. doi:10.1128/AAC.43.10.2444
  • Kaiser L, Crump CE, Hayden FG. In vitro activity of pleconaril and AG7088 against selected serotypes and clinical isolates of human rhinoviruses. Antiviral Res. 2000;47(3):215–220. doi:10.1016/S0166-3542(00)00106-6
  • Zalman LS, Brothers MA, Dragovich PS, et al. Inhibition of human rhinovirus-induced cytokine production by AG7088, a human rhinovirus 3C protease inhibitor. Antimicrob Agents Chemother. 2000;44(5):1236–1241. doi:10.1128/AAC.44.5.1236-1241.2000
  • Hsyu PH, Yk P, Gersten M, Penning CA, Kerr BM. Pharmacokinetics and safety of an antirhinoviral agent, ruprintrivir, in healthy volunteers. Antimicrob Agents Chemother. 2002;46(2):392–397.
  • Hayden FG, Turner RB, Gwaltney JM, et al. Phase II, randomized, double-blind, placebo-controlled studies of ruprintrivir nasal spray 2-percent suspension for prevention and treatment of experimentally induced rhinovirus colds in healthy volunteers. Antimicrob Agents Chemother. 2003;47(12):3907–3916. doi:10.1128/AAC.47.12.3907-3916.2003
  • Kawatkar SP, Gagnon M, Hoesch V, et al. Design and structure-activity relationships of novel inhibitors of human rhinovirus 3C protease. Bioorg Med Chem Lett. 2016;26(14):3248–3252. doi:10.1016/j.bmcl.2016.05.066
  • Sanders SP, Siekierski ES, Porter JD, Richards SM, Proud D. Nitric oxide inhibits rhinovirus-induced cytokine production and viral replication in a human respiratory epithelial cell line. J Virol. 1998;72(2):934–942. doi:10.1128/JVI.72.2.934-942.1998
  • Yang Z, Bochkov YA, Voelker DR, Foster MW, Que LG. Identification of a novel inhibitor of human rhinovirus replication and inflammation in airway epithelial cells. Am J Respir Cell Mol Biol. 2019;60(1):58–67. doi:10.1165/rcmb.2018-0058OC
  • Shim A, Song JH, Kwon BE, et al. Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model. Sci Rep. 2016;6:23110. doi:10.1038/srep23110
  • Sousa FH, Casanova V, Findlay F, et al. Cathelicidins display conserved direct antiviral activity towards rhinovirus. Peptides. 2017;95:76–83. doi:10.1016/j.peptides.2017.07.013
  • Hansdottir S, Monick MM, Hinde SL, Lovan N, Look DC, Hunninghake GW. Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol. 2008;181(10):7090–7099. doi:10.4049/jimmunol.181.10.7090
  • Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770–1773. doi:10.1126/science.1123933
  • Telcian AG, Zdrenghea MT, Edwards MR, et al. Vitamin D increases the antiviral activity of bronchial epithelial cells in vitro. Antiviral Res. 2017;137:93–101. doi:10.1016/j.antiviral.2016.11.004
  • Schögler A, Muster RJ, Kieninger E, et al. Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37. Eur Respir J. 2016;47(2):520–530. doi:10.1183/13993003.00665-2015
  • Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients. 2015;7(6):4240–4270. doi:10.3390/nu7064240
  • Jolliffe DA, Greiller CL, Mein CA, et al. Vitamin D receptor genotype influences risk of upper respiratory infection. Br J Nutr. 2018;120(8):891–900. doi:10.1017/S000711451800209X
  • Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583
  • Martineau AR, Jolliffe DA, Greenberg L, et al. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol Assess. 2019;23(2):1–44. doi:10.3310/hta23020
  • McCrae C, Olsson M, Gustafson P, et al. INEXAS: a phase 2 randomized trial of on-demand inhaled interferon beta-1a in severe asthmatics. Clin Exp Allergy. 2021;51(2):273–283. doi:10.1111/cea.13765
  • Watson A, Spalluto CM, McCrae C, et al. Dynamics of IFN-β responses during respiratory viral infection. Insights for therapeutic strategies. Am J Respir Crit Care Med. 2020;201(1):83–94. doi:10.1164/rccm.201901-0214OC
  • Monk PD, Marsden RJ, Tear VJ, et al. Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021;9(2):196–206. doi:10.1016/S2213-2600(20)30511-7
  • Gielen V, Johnston SL, Edwards MR. Azithromycin induces anti-viral responses in bronchial epithelial cells. Eur Respir J. 2010;36(3):646–654. doi:10.1183/09031936.00095809
  • Porter JD, Watson J, Roberts LR, et al. Identification of novel macrolides with antibacterial, anti-inflammatory and type I and III IFN-augmenting activity in airway epithelium. J Antimicrob Chemother. 2016;71(10):2767–2781. doi:10.1093/jac/dkw222
  • Menzel M, Akbarshahi H, Bjermer L, Uller L. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients. Sci Rep. 2016;28(6):28698. doi:10.1038/srep28698
  • Mejdrová I, Chalupská D, Plačková P, et al. Rational design of novel highly potent and selective phosphatidylinositol 4-kinase IIIβ (PI4KB) inhibitors as broad-spectrum antiviral agents and tools for chemical biology. J Med Chem. 2017;60(1):100–118. doi:10.1021/acs.jmedchem.6b01465
  • Greninger AL, Knudsen GM, Betegon M, Burlingame AL, Derisi JL. The 3A protein from multiple picornaviruses utilizes the golgi adaptor protein ACBD3 to recruit PI4KIIIβ. J Virol. 2012;86(7):3605–3616. doi:10.1128/JVI.06778-11
  • Arita M, Kojima H, Nagano T, Okabe T, Wakita T, Shimizu H. Oxysterol-binding protein family I is the target of minor enviroxime-like compounds. J Virol. 2013;87(8):4252–4260. doi:10.1128/JVI.03546-12
  • Guedán A, Swieboda D, Charles M, et al. Investigation of the role of protein kinase D in human rhinovirus replication. J Virol. 2017;91(9). doi:10.1128/JVI.00217-17
  • Tóth B, Balla A, Ma H, Knight ZA, Shokat KM, Balla T. Phosphatidylinositol 4-kinase IIIbeta regulates the transport of ceramide between the endoplasmic reticulum and Golgi. J Biol Chem. 2006;281(47):36369–36377. doi:10.1074/jbc.M604935200
  • Mousnier A, Bell AS, Swieboda DP, et al. Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus. Nat Chem. 2018;10(6):599–606. doi:10.1038/s41557-018-0039-2
  • Carey BS, Barclay WS, Russell SM, Tyrrell DA. The specificity of antibodies induced by infection with rhinovirus type 2. J Med Virol. 1992;36(4):251–258. doi:10.1002/jmv.1890360404
  • Hastings GZ, Speller SA, Francis MJ. Neutralizing antibodies to human rhinovirus produced in laboratory animals and humans that recognize a linear sequence from VP2. J Gen Virol. 1990;71(Pt 12)):3055–3059. doi:10.1099/0022-1317-71-12-3055
  • Hayden FG, Gwaltney JM, Colonno RJ. Modification of experimental rhinovirus colds by receptor blockade. Antiviral Res. 1988;9(4):233–247. doi:10.1016/0166-3542(88)90055-1
  • Traub S, Nikonova A, Carruthers A, et al. An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation. PLoS Pathog. 2013;9(8):e1003520. doi:10.1371/journal.ppat.1003520
  • Kim S-R, Song J-H, Ahn J-H, et al. Antiviral and anti-inflammatory activity of budesonide against human rhinovirus infection mediated via autophagy activation. Antiviral Res. 2018;151:87–96. doi:10.1016/j.antiviral.2018.01.012
  • Kang H, Kim C, Kim D, et al. Synergistic antiviral activity of gemcitabine and ribavirin against enteroviruses. Antiviral Res. 2015;124:1–10. doi:10.1016/j.antiviral.2015.10.011
  • Song JH, Kim SR, Heo EY, et al. Antiviral activity of gemcitabine against human rhinovirus in vitro and in vivo. Antiviral Res. 2017;145:6–13. doi:10.1016/j.antiviral.2017.07.003
  • Ganesan S, Faris AN, Comstock AT, et al. Quercetin inhibits rhinovirus replication in vitro and in vivo. Antiviral Res. 2012;94(3):258–271. doi:10.1016/j.antiviral.2012.03.005
  • Farazuddin M, Mishra R, Jing Y, Srivastava V, Comstock AT, Sajjan US. Quercetin prevents rhinovirus-induced progression of lung disease in mice with COPD phenotype. PLoS One. 2018;13(7):e0199612. doi:10.1371/journal.pone.0199612
  • Han MK, Barreto TA, Martinez FJ, Comstock AT, Sajjan US. Randomised clinical trial to determine the safety of quercetin supplementation in patients with chronic obstructive pulmonary disease. BMJ Open Respir Res. 2020;7(1):e000392. doi:10.1136/bmjresp-2018-000392
  • Da Costa L, Scheers E, Coluccia A, et al. Heterocyclic pharmacochemistry of new rhinovirus antiviral agents: a combined computational and experimental study. Eur J Med Chem. 2017;140:528–541. doi:10.1016/j.ejmech.2017.09.036
  • Nguyen A, Guedán A, Mousnier A, et al. Host lipidome analysis during rhinovirus replication in HBECs identifies potential therapeutic targets. J Lipid Res. 2018;59(9):1671–1684. doi:10.1194/jlr.M085910
  • Valbuena A, Rodríguez-Huete A, Mateu MG. Mechanical stiffening of human rhinovirus by cavity-filling antiviral drugs. Nanoscale. 2018;10(3):1440–1452. doi:10.1039/C7NR08704G