Immunity Cell Responses to RSV and the Role of Antiviral Inhibitors: A Systematic Review

References

• Lukacs NW, Smit JJ, Mukherjee S, Morris SB, Nunez G, Lindell DM. Respiratory virus-induced TLR7 activation controls IL-17–associated increased mucus via IL-23 regulation. J Immunol. 2010;185(4):2231–2239. doi:10.4049/jimmunol.1000733
   Web of Science ®Google Scholar
• Heminway B, Yu Y, Tanaka Y, et al. Analysis of respiratory syncytial virus F, G, and SH proteins in cell fusion. Virology. 1994;200(2):801–805. doi:10.1006/viro.1994.1245
   PubMed Web of Science ®Google Scholar
• Murawski MR, Bowen GN, Cerny AM, et al. Respiratory syncytial virus activates innate immunity through Toll-like receptor 2. J Virol. 2009;83(3):1492–1500. doi:10.1128/JVI.00671-08
   PubMed Web of Science ®Google Scholar
• Van der Gucht W, Leemans A, De Schryver M, et al. Respiratory syncytial virus (RSV) entry is inhibited by serine protease inhibitor AEBSF when present during an early stage of infection. Virol J. 2017;14(1):1–10. doi:10.1186/s12985-017-0824-3
   Web of Science ®Google Scholar
• Jafri HS, Wu X, Makari D, Henrickson KJ. Distribution of respiratory syncytial virus subtypes A and B among infants presenting to the emergency department with lower respiratory tract infection or apnea. Pediatr Infect Dis J. 2013;32(4):335–340. doi:10.1097/INF.0b013e318282603a
   Web of Science ®Google Scholar
• Zhang L, Peeples ME, Boucher RC, Collins PL, Pickles RJ. Respiratory syncytial virus infection of human airway epithelial cells is polarized, specific to ciliated cells, and without obvious cytopathology. J Virol. 2002;76(11):5654–5666. doi:10.1128/JVI.76.11.5654-5666.2002
   PubMed Web of Science ®Google Scholar
• Chirkova T, Lin S, Oomens AG, et al. CX3CR1 is an important surface molecule for respiratory syncytial virus infection in human airway epithelial cells. J Gen Virol. 2015;96(Pt 9):2543. doi:10.1099/vir.0.000218
   Web of Science ®Google Scholar
• Orumie UC, Bartholomew DC. Respiratory syncytial virus infection in infants: a comparative study using discriminant. Probit Logistic Regression Analysis. 2022;1:654.
   Google Scholar
• Pickles RJ, DeVincenzo JP. Respiratory syncytial virus (RSV) and its propensity for causing bronchiolitis. J Pathol. 2015;235(2):266–276. doi:10.1002/path.4462
   PubMed Web of Science ®Google Scholar
• Siefker D, Vu L, You D, et al. Respiratory syncytial virus disease severity is associated with distinct CD8+ T cell profiles. Am Assoc Immnol. 2019;2:8465.
   Google Scholar
• Domachowske JB, Rosenberg HF. Respiratory syncytial virus infection: immune response, immunopathogenesis, and treatment. Clin Microbiol Rev. 1999;12(2):298–309. doi:10.1128/CMR.12.2.298
   PubMed Web of Science ®Google Scholar
• CDC 24/7: respiratory Syncytial Virus Infection (RSV). Available from: https://www.cdc.gov/rsv/about/symptoms.html. Accessed November 24, 2022.
   Google Scholar
• WHO. Respiratory Syncytial Virus Surveillance. Available from: https://www.who.int/teams/global-influenza-programme/global-respiratory-syncytial-virus-surveillance. Accessed November 24, 2022.
   Google Scholar
• Gagro A, Tominac M, Kršulović-Hrešić V, et al. Increased Toll-like receptor 4 expression in infants with respiratory syncytial virus bronchiolitis. Clin Exp Immunol. 2004;135(2):267–272. doi:10.1111/j.1365-2249.2004.02364.x
   Web of Science ®Google Scholar
• Kurt-Jones EA, Popova L, Kwinn L, et al. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol. 2000;1(5):398–401. doi:10.1038/80833
   PubMed Web of Science ®Google Scholar
• McDermott DS, Weiss KA, Knudson CJ, Varga SM. Central role of dendritic cells in shaping the adaptive immune response during respiratory syncytial virus infection. Future Virol. 2011;6(8):963–973. doi:10.2217/fvl.11.62
   Web of Science ®Google Scholar
• Granot T, Senda T, Carpenter DJ, et al. Dendritic cells display subset and tissue-specific maturation dynamics over human life. Immunity. 2017;46(3):504–515. doi:10.1016/j.immuni.2017.02.019
   PubMed Web of Science ®Google Scholar
• Kerrin A, Fitch P, Errington C, et al. Differential lower airway dendritic cell patterns may reveal distinct endotypes of RSV bronchiolitis. Thorax. 2017;72(7):620–627. doi:10.1136/thoraxjnl-2015-207358
   PubMed Web of Science ®Google Scholar
• Weng K, Zhang J, Mei X, et al. Lower number of plasmacytoid dendritic cells in peripheral blood of children with bronchiolitis following respiratory syncytial virus infection. Influenza Other Respi Viruses. 2014;8(4):469–473. doi:10.1111/irv.12242
   Web of Science ®Google Scholar
• de Graaff PM, de Jong EC, van Capel TM, et al. Respiratory syncytial virus infection of monocyte-derived dendritic cells decreases their capacity to activate CD4 T cells. J Immunol. 2005;175(9):5904–5911. doi:10.4049/jimmunol.175.9.5904
   Web of Science ®Google Scholar
• Gill MA, Long K, Kwon T, et al. Differential recruitment of dendritic cells and monocytes to respiratory mucosal sites in children with influenza virus or respiratory syncytial virus infection. J Infect Dis. 2008;198(11):1667–1676. doi:10.1086/593018
   Web of Science ®Google Scholar
• Schijf MA, Lukens MV, Kruijsen D, et al. Respiratory syncytial virus induced type I IFN production by pDC is regulated by RSV-infected airway epithelial cells, RSV-exposed monocytes and virus specific antibodies. PLoS One. 2013;8(11):e81695. doi:10.1371/journal.pone.0081695
   Web of Science ®Google Scholar
• Kim TH, Lee HK. Differential roles of lung dendritic cell subsets against respiratory virus infection. Immune Netw. 2014;14(3):128–137. doi:10.4110/in.2014.14.3.128
   Google Scholar
• Pribul PK, Harker J, Wang B, et al. Alveolar macrophages are a major determinant of early responses to viral lung infection but do not influence subsequent disease development. J Virol. 2008;82(9):4441–4448. doi:10.1128/JVI.02541-07
   PubMed Web of Science ®Google Scholar
• Makris S, Bajorek M, Culley FJ, Goritzka M, Johansson C. Alveolar macrophages can control respiratory syncytial virus infection in the absence of type I interferons. J Innate Immun. 2016;8(5):452–463. doi:10.1159/000446824
   Web of Science ®Google Scholar
• Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010;32(5):593–604. doi:10.1016/j.immuni.2010.05.007
   PubMed Web of Science ®Google Scholar
• Shirey KA, Pletneva LM, Puche AC, et al. Control of RSV-induced lung injury by alternatively activated macrophages is IL-4Rα-, TLR4-, and IFN-β-dependent. Mucosal Immunol. 2010;3(3):291–300. doi:10.1038/mi.2010.6
   Web of Science ®Google Scholar
• Bhat R, Farrag MA, Almajhdi FN. Double-edged role of natural killer cells during RSV infection. Int Rev Immunol. 2020;39(5):233–244. doi:10.1080/08830185.2020.1770748
   PubMed Web of Science ®Google Scholar
• Zdrenghea M, Telcian AG, Laza-Stanca V, et al. RSV infection modulates IL-15 production and MICA levels in respiratory epithelial cells. Eur Respir J. 2012;39(3):712–720. doi:10.1183/09031936.00099811
   PubMed Web of Science ®Google Scholar
• Li F, Zhu H, Sun R, Wei H, Tian Z. Natural killer cells are involved in acute lung immune injury caused by respiratory syncytial virus infection. J Virol. 2012;86(4):2251–2258. doi:10.1128/JVI.06209-11
   PubMed Web of Science ®Google Scholar
• van Erp EA, Feyaerts D, Duijst M, et al. Respiratory syncytial virus infects primary neonatal and adult natural killer cells and affects their antiviral effector function. J Infect Dis. 2019;219(5):723–733. doi:10.1093/infdis/jiy566
   PubMed Web of Science ®Google Scholar
• Roduit C, Frei R, Ferstl R, et al. Late-Breaking Abstracts Presented At Scientific Sessions AAAAI Annual Meeting March 4-7, 2016. J Allergy Clin Immunol. 2016;137(2):89.
   Google Scholar
• Lee SY, Noh Y, Goo JH, et al. Natural killer T cell sensitization during neonatal respiratory syncytial virus infection induces eosinophilic lung disease in re-infected adult mice. PLoS One. 2017;12(6):e0176940. doi:10.1371/journal.pone.0176940
   PubMed Web of Science ®Google Scholar
• Kirsebom F, Michalaki C, Agueda-Oyarzabal M, Johansson C. Neutrophils do not impact viral load or the peak of disease severity during RSV infection. Sci Rep. 2020;10(1):1–12. doi:10.1038/s41598-020-57969-w
   Web of Science ®Google Scholar
• Johnson JE, Gonzales RA, Olson SJ, Wright PF, Graham BS. The histopathology of fatal untreated human respiratory syncytial virus infection. Modern Pathology. 2007;20(1):108–119. doi:10.1038/modpathol.3800725
   Web of Science ®Google Scholar
• Cortjens B, De Boer OJ, De Jong R, et al. Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease. J Pathol. 2016;238(3):401–411. doi:10.1002/path.4660
   PubMed Web of Science ®Google Scholar
• Wang S-Z, Smith P, Lovejoy M, Bowden J, Alpers J, Forsyth K. The apoptosis of neutrophils is accelerated in respiratory syncytial virus (RSV)-induced bronchiolitis. Clin Exp Immunol. 1998;114(1):49–54. doi:10.1046/j.1365-2249.1998.00681.x
   Web of Science ®Google Scholar
• Sabbaghi A, Miri SM, Keshavarz M, Mahooti M, Zebardast A, Ghaemi A. Role of γδ T cells in controlling viral infections with a focus on influenza virus: implications for designing novel therapeutic approaches. Virol J. 2020;17(1):1–18. doi:10.1186/s12985-020-01449-0
   Web of Science ®Google Scholar
• Aoyagi M, Shimojo N, Sekine K, Nishimuta T, Kohno Y. Respiratory syncytial virus infection suppresses IFN-γ production of γδ T cells. Clin Exp Immunol. 2003;131(2):312–317. doi:10.1046/j.1365-2249.2003.02062.x
   Web of Science ®Google Scholar
• Stoppelenburg AJ, Salimi V, Hennus M, Plantinga M. Local IL-17A potentiates early neutrophil recruitment to the respiratory tract during severe RSV infection. PLoS One. 2013;8(10):e78461. doi:10.1371/journal.pone.0078461
   PubMed Web of Science ®Google Scholar
• Huang H, Saravia J, You D, Shaw AJ, Cormier SA. Impaired gamma delta T cell‐derived IL‐17A and inflammasome activation during early respiratory syncytial virus infection in infants. Immunol Cell Biol. 2015;93(2):126–135. doi:10.1038/icb.2014.79
   PubMed Web of Science ®Google Scholar
• Démoulins T, Brügger M, Zumkehr B, et al. The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis. PLoS Pathog. 2021;17(4):e1009529. doi:10.1371/journal.ppat.1009529
   PubMed Web of Science ®Google Scholar
• Raiden S, Sananez I, Remes-Lenicov F, et al. Respiratory syncytial virus (RSV) infects CD4+ T cells: frequency of circulating CD4+ RSV+ T cells as a marker of disease severity in young children. J Infect Dis. 2017;215(7):1049–1058. doi:10.1093/infdis/jix070
   Web of Science ®Google Scholar
• Graham B, Bunton L, Wright P, Karzon D. Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice. J Clin Invest. 1991;88(3):1026–1033. doi:10.1172/JCI115362
   PubMed Web of Science ®Google Scholar
• Anderson J, Norden J, Saunders D, Toms G, Scott R. Analysis of the local and systemic immune responses induced in BALB/c mice by experimental respiratory syncytial virus infection. J General Virol. 1990;71(7):1561–1570. doi:10.1099/0022-1317-71-7-1561
   Web of Science ®Google Scholar
• Cherrie AH, Anderson K, Wertz GW, Openshaw P. Human cytotoxic T cells stimulated by antigen on dendritic cells recognize the N, SH, F, M, 22K, and 1b proteins of respiratory syncytial virus. J Virol. 1992;66(4):2102–2110. doi:10.1128/jvi.66.4.2102-2110.1992
   Web of Science ®Google Scholar
• Srikiatkhachorn A, Braciale TJ. Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection. J Exp Med. 1997;186(3):421–432. doi:10.1084/jem.186.3.421
   PubMed Web of Science ®Google Scholar
• Muñoz JL, McCarthy C, Clark M, Hall C. Respiratory syncytial virus infection in C57BL/6 mice: clearance of virus from the lungs with virus-specific cytotoxic T cells. J Virol. 1991;65(8):4494–4497. doi:10.1128/jvi.65.8.4494-4497.1991
   Web of Science ®Google Scholar
• Weiss KA, Christiaansen AF, Fulton RB, Meyerholz DK, Varga SM. Multiple CD4+ T cell subsets produce immunomodulatory IL-10 during respiratory syncytial virus infection. J Immunol. 2011;187(6):3145–3154. doi:10.4049/jimmunol.1100764
   Web of Science ®Google Scholar
• Sun J, Cardani A, Sharma AK, et al. Autocrine regulation of pulmonary inflammation by effector T-cell derived IL-10 during infection with respiratory syncytial virus. PLoS Pathog. 2011;7(8):e1002173. doi:10.1371/journal.ppat.1002173
   Web of Science ®Google Scholar
• Lukens MV, van de Pol AC, Coenjaerts FE, et al. A systemic neutrophil response precedes robust CD8+ T-cell activation during natural respiratory syncytial virus infection in infants. J Virol. 2010;84(5):2374–2383. doi:10.1128/JVI.01807-09
   PubMed Web of Science ®Google Scholar
• Siefker DT, Vu L, You D, et al. Respiratory syncytial virus disease severity is associated with distinct CD8+ T-cell profiles. Am J Respir Crit Care Med. 2020;201(3):325–334. doi:10.1164/rccm.201903-0588OC
   Web of Science ®Google Scholar
• Mukherjee S, Lindell DM, Berlin AA, et al. IL-17–induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease. Am J Pathol. 2011;179(1):248–258. doi:10.1016/j.ajpath.2011.03.003
   PubMed Web of Science ®Google Scholar
• Bermejo-Martin JF, Garcia-Arevalo MC, Lejarazu ROD, et al. Predominance of Th2 cytokines, CXC chemokines and innate immunity mediators at the mucosal level during severe respiratory syncytial virus infection in children. Eur Cytokine Netw. 2007;18(3):163.
   Web of Science ®Google Scholar
• Ye Q, Shao WX, Shang SQ, Pan YX, Shen HQ, Chen XJ. Epidemiological characteristics and immune status of children with Respiratory Syncytial Virus. J Med Virol. 2015;87(2):323–329. doi:10.1002/jmv.24047
   Web of Science ®Google Scholar
• Fernández JA, Roine I, Vasquez A, Cáneo M. Soluble interleukin-2 receptor (sCD25) and interleukin-10 plasma concentrations are associated with severity of primary respiratory syncytial virus (RSV) infection. Eur Cytokine Netw. 2005;16(1):81–90.
   Web of Science ®Google Scholar
• Sung RYT, Hui SHL, Wong CK, Lam CWK, Yin J. A comparison of cytokine responses in respiratory syncytial virus and influenza A infections in infants. Eur J Pediatr. 2001;160(2):117–122. doi:10.1007/s004310000676
   PubMed Web of Science ®Google Scholar
• Roumanes D, Falsey A, Quataert S, et al. T-cell responses in adults during natural respiratory syncytial virus infection. J Infect Dis. 2018;218(3):418–428. doi:10.1093/infdis/jiy016
   PubMed Web of Science ®Google Scholar
• Fulton RB, Meyerholz DK, Varga SM. Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection. J Immunol. 2010;185(4):2382–2392. doi:10.4049/jimmunol.1000423
   PubMed Web of Science ®Google Scholar
• Lee DC, Harker JA, Tregoning JS, et al. CD25+ natural regulatory T cells are critical in limiting innate and adaptive immunity and resolving disease following respiratory syncytial virus infection. J Virol. 2010;84(17):8790–8798. doi:10.1128/JVI.00796-10
   PubMed Web of Science ®Google Scholar
• Durant LR, Makris S, Voorburg CM, Loebbermann J, Johansson C, Openshaw PJ. Regulatory T cells prevent Th2 immune responses and pulmonary eosinophilia during respiratory syncytial virus infection in mice. J Virol. 2013;87(20):10946–10954. doi:10.1128/JVI.01295-13
   PubMed Web of Science ®Google Scholar
• Zhivaki D, Lemoine S, Lim A, et al. Respiratory syncytial virus infects regulatory B cells in human neonates via chemokine receptor CX3CR1 and promotes lung disease severity. Immunity. 2017;46(2):301–314. doi:10.1016/j.immuni.2017.01.010
   Web of Science ®Google Scholar
• Jansen K, Cevhertas L, Ma S, Satitsuksanoa P, Akdis M. Regulatory B cells, A to Z. Allergy. 2021;76(9):2699–2715. doi:10.1111/all.14763
   PubMed Web of Science ®Google Scholar
• Openshaw PJ. RSV takes control of neonatal Breg cells: two hands on the wheel. Immunity. 2017;46(2):171–173. doi:10.1016/j.immuni.2017.01.011
   Web of Science ®Google Scholar
• Lou Z, Sun Y, Rao Z. Current progress in antiviral strategies. Trends Pharmacol Sci. 2014;35(2):86–102. doi:10.1016/j.tips.2013.11.006
   PubMed Web of Science ®Google Scholar
• Olszewska W, Ispas G, Schnoeller C, et al. Antiviral and lung protective activity of a novel respiratory syncytial virus fusion inhibitor in a mouse model. Eur Respir J. 2011;38(2):401–408. doi:10.1183/09031936.00005610
   Web of Science ®Google Scholar
• Roymans D, Alnajjar SS, Battles MB, et al. Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor. Nat Commun. 2017;8(1):1–15. doi:10.1038/s41467-017-00170-x
   Web of Science ®Google Scholar
• Rhodin M, McAllister N, Kim I, et al., EP-023938, A Novel Non-fusion Replication Inhibitor of Respiratory Syncytial Virus (RSV). Poster presented at 10th International Respiratory Syncytial Virus Symposium (RSV 2016), Patagonia, Argentina, 2016.
   Google Scholar
• Razinkov V, Gazumyan A, Nikitenko A, Ellestad G, Krishnamurthy G. RFI-641 inhibits entry of respiratory syncytial virus via interactions with fusion protein. Chem Biol. 2001;8(7):645–659. doi:10.1016/S1074-5521(01)00042-4
   PubMedGoogle Scholar
• Razinkov V, Huntley C, Ellestad G, Krishnamurthy G. RSV entry inhibitors block F-protein mediated fusion with model membranes. Antiviral Res. 2002;55(1):189–200. doi:10.1016/S0166-3542(02)00050-5
   Web of Science ®Google Scholar
• Huntley CC, Weiss WJ, Gazumyan A, et al. RFI-641, a potent respiratory syncytial virus inhibitor. Antimicrob Agents Chemother. 2002;46(3):841–847. doi:10.1128/AAC.46.3.841-847.2002
   PubMed Web of Science ®Google Scholar
• Ispas G, Koul A, Verbeeck J, et al. Antiviral activity of TMC353121, a respiratory syncytial virus (RSV) fusion inhibitor, in a non-human primate model. PLoS One. 2015;10(5):e0126959. doi:10.1371/journal.pone.0126959
   PubMed Web of Science ®Google Scholar
• Kocienski P. Synthesis of Ziresovir. Synfacts. 2019;15(10):1100.
   Google Scholar
• Zheng X, Gao L, Wang L, et al. Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable Respiratory Syncytial Virus Fusion Protein Inhibitor. ACS Publications; 2019.
   Google Scholar
• Esimone C, Eck G, Duong T, Überla K, Proksch P, Grunwald T. Potential anti-respiratory syncytial virus lead compounds from Aglaia species. Int J Pharmaceutical Sci. 2008;63(10):768–773.
   Google Scholar
• Chu HY, Englund JA. Respiratory syncytial virus disease: prevention and treatment. In: Challenges and Opportunities for Respiratory Syncytial Virus Vaccines. Springer; 2013:235–258.
   Google Scholar
• Maggon K, Barik S. New drugs and treatment for respiratory syncytial virus. Rev Med Virol. 2004;14(3):149–168. doi:10.1002/rmv.423
   Web of Science ®Google Scholar
• Krilov LR. Respiratory syncytial virus disease: update on treatment and prevention. Expert Rev Anti Infect Ther. 2011;9(1):27–32. doi:10.1586/eri.10.140
   PubMed Web of Science ®Google Scholar
• Parker WB. Metabolism and antiviral activity of ribavirin. Virus Res. 2005;107(2):165–171. doi:10.1016/j.virusres.2004.11.006
   PubMed Web of Science ®Google Scholar
• Leyssen P, Balzarini J, De Clercq E, Neyts J. The predominant mechanism by which ribavirin exerts its antiviral activity in vitro against flaviviruses and paramyxoviruses is mediated by inhibition of IMP dehydrogenase. J Virol. 2005;79(3):1943–1947. doi:10.1128/JVI.79.3.1943-1947.2005
   PubMed Web of Science ®Google Scholar
• Pollack PF, Groothuis JR, Barbarotto G. Development and use of palivizumab (Synagis): a passive immunoprophylactic agent for RSV. J Infection Chemother. 2002;8(3):201–206. doi:10.1007/s10156-002-0178-6
   Google Scholar
• Narayan O, Bentley A, Mowbray K, et al. Updated cost-effectiveness analysis of palivizumab (Synagis) for the prophylaxis of respiratory syncytial virus in infant populations in the UK. J Med Econ. 2020;23(12):1640–1652. doi:10.1080/13696998.2020.1836923
   PubMed Web of Science ®Google Scholar
• Bont L. Palivizumab (Synagis^®). Handbook of Therapeutic Antibodies; 2014:1825–1854.
   Google Scholar
• Cianci C, Meanwell N, Krystal M. Antiviral activity and molecular mechanism of an orally active respiratory syncytial virus fusion inhibitor. J Antimicrobial Chemother. 2005;55(3):289–292. doi:10.1093/jac/dkh558
   Web of Science ®Google Scholar
• Cianci C, Yu K-L, Combrink K, et al. Orally active fusion inhibitor of respiratory syncytial virus. Antimicrob Agents Chemother. 2004;48(2):413–422. doi:10.1128/AAC.48.2.413-422.2004
   PubMed Web of Science ®Google Scholar
• Feng S, Hong D, Wang B, et al. Discovery of imidazopyridine derivatives as highly potent respiratory syncytial virus fusion inhibitors. ACS Med Chem Lett. 2015;6(3):359–362. doi:10.1021/acsmedchemlett.5b00008
   PubMed Web of Science ®Google Scholar
• Rhodin MH, McAllister NV, Castillo J, et al. EDP-938, a novel nucleoprotein inhibitor of respiratory syncytial virus, demonstrates potent antiviral activities in vitro and in a non-human primate model. PLoS Pathog. 2021;17(3):e1009428. doi:10.1371/journal.ppat.1009428
   PubMed Web of Science ®Google Scholar
• Ahmad A, Eze K, Noulin N, et al. EDP-938, a respiratory syncytial virus inhibitor, in a human virus challenge. N Eng J Med. 2022;386(7):655–666. doi:10.1056/NEJMoa2108903
   Web of Science ®Google Scholar
• Cox RM, Toots M, Yoon -J-J, et al. Development of an allosteric inhibitor class blocking RNA elongation by the respiratory syncytial virus polymerase complex. J Biol Chem. 2018;293(43):16761–16777. doi:10.1074/jbc.RA118.004862
   Web of Science ®Google Scholar
• Coates M, Brookes D, Kim Y-I, et al. Preclinical characterization of PC786, an inhaled small-molecule respiratory syncytial virus L protein polymerase inhibitor. Antimicrob Agents Chemother. 2017;61(9):e00737–17. doi:10.1128/AAC.00737-17
   PubMed Web of Science ®Google Scholar
• Coates M, Brookes D, Allen H, et al. Preclinical characterization of PC786, a potent antiviral inhibitor of respiratory syncytial virus replication. virus. 2016;1:2.
   Google Scholar
• Zhang G-N, Li Q, Zhao J, et al. Design and synthesis of 2-((1H-indol-3-yl) thio)-N-phenyl-acetamides as novel dual inhibitors of respiratory syncytial virus and influenza virus A. Eur J Med Chem. 2020;186:111861. doi:10.1016/j.ejmech.2019.111861
   PubMed Web of Science ®Google Scholar
• Brookes DW, Coates M, Allen H, et al. Late therapeutic intervention with a respiratory syncytial virus L‐protein polymerase inhibitor, PC786, on respiratory syncytial virus infection in human airway epithelium. Br J Pharmacol. 2018;175(12):2520–2534. doi:10.1111/bph.14221
   PubMed Web of Science ®Google Scholar
• Van der Gucht W. Characterization of Clinical Respiratory Syncytial Virus Isolates and the Effect of Protease Inhibitors on Early Viral Entry. University of Antwerp; 2019.
   Google Scholar
• Vendeville S, Tahri A, Hu L, et al. Discovery of 3-({5-Chloro-1-[3-(methylsulfonyl) propyl]-1 H-indol-2-yl} methyl)-1-(2, 2, 2-trifluoroethyl)-1, 3-dihydro-2 H-imidazo [4, 5-c] pyridin-2-one (JNJ-53718678), a Potent and Orally Bioavailable Fusion Inhibitor of Respiratory Syncytial Virus. J Med Chem. 2020;63(15):8046–8058. doi:10.1021/acs.jmedchem.0c00226
   Web of Science ®Google Scholar
• Xing Y, Proesmans M. New therapies for acute RSV infections: where are we? Eur J Pediatr. 2019;178(2):131–138. doi:10.1007/s00431-018-03310-7
   PubMed Web of Science ®Google Scholar
• Tang W, Li M, Liu Y, et al. Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane. FASEB J. 2019;33(3):4287–4299. doi:10.1096/fj.201800579R
   Web of Science ®Google Scholar
• Kim YI, Pareek R, Murphy R, et al. The antiviral effects of RSV fusion inhibitor, MDT‐637, on clinical isolates, vs its achievable concentrations in the human respiratory tract and comparison to ribavirin. Influenza Other Respi Viruses. 2017;11(6):525–530. doi:10.1111/irv.12503
   PubMed Web of Science ®Google Scholar