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Chapter 14 : Antirespiratory Virus Agents

Authors: Marcus R. Pereira1, Benjamin A. Miko2, Monica Mehta3, Scott M. Hammer4
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Affiliations: 1: Assistant Professor of Medicine, Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, NewYork-Presbyterian Hospital, New York, NY, USA; 2: Assistant Professor of Medicine, Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, NewYork-Presbyterian Hospital, New York, NY, USA; 3: Clinical Pharmacy Manager, Clinical Manager, Infectious Diseases, NewYork-Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA.; 4: Harold C. Neu Professor of Medicine, Chief, Division of Infectious Diseases, Department of Medicine Columbia University Medical Center, NewYork-Presbyterian Hospital, New York, NY, USA.
Content Type: Reference
Publication Year: 2017

Category: Viruses and Viral Pathogenesis

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Abstract:

This chapter reviews antiviral agents that have been, or are being, developed to treat or prevent respiratory viral infections. Detailed information is provided for approved agents and those in more advanced stages of clinical development. Agents in Phase I human studies or promising approaches that are still in preclinical development are described briefly. The reader is referred to the respective pathogen-specific chapters for full discussions of the viral agents and the diseases they cause.

Citation: Pereira M, Miko B, Mehta M, Hammer S. 2017. Antirespiratory Virus Agents, p 271-290. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch14
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Antirespiratory Virus Agents
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Citation: Pereira M, Miko B, Mehta M, Hammer S. 2017. Antirespiratory Virus Agents, p 271-290. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch14
/content/10.1128/9781555819439.ch14.ch14fig1
FIGURE 1

Molecular structures of M2 protein inhibitors amantadine (A) and rimantadine (B).

10.1128/9781555819439/9439ch14fig1_thmb.gif
10.1128/9781555819439/9439ch14fig1.gif
Image of FIGURE 1
FIGURE 1

Molecular structures of M2 protein inhibitors amantadine (A) and rimantadine (B).

Citation: Pereira M, Miko B, Mehta M, Hammer S. 2017. Antirespiratory Virus Agents, p 271-290. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch14
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/content/10.1128/9781555819439.ch14.ch14fig2
FIGURE 2

Replicative cycle of influenza virus. The influenza virus is shown binding to the surface of an airway epithelial cell via the interaction of hemagglutinin (HA) with sialic acid residues. HA is subsequently cleaved by a protease, and the virus is endocytosed. The M2 protein allows hydrogen ions to enter the virion, promoting the dissociation of ribonuclear protein and release of viral nucleic acids into the cytoplasm (uncoating). Viral RNA replication occurs in the nucleus by the viral RNA polymerase (RNAp) complex. Following replication of viral RNA and synthesis of structural/nonstructural proteins, virions are assembled and released. Sites of action of antiviral compounds are shown by a solid line.

10.1128/9781555819439/9439ch14fig2_thmb.gif
10.1128/9781555819439/9439ch14fig2.gif
Image of FIGURE 2
FIGURE 2

Replicative cycle of influenza virus. The influenza virus is shown binding to the surface of an airway epithelial cell via the interaction of hemagglutinin (HA) with sialic acid residues. HA is subsequently cleaved by a protease, and the virus is endocytosed. The M2 protein allows hydrogen ions to enter the virion, promoting the dissociation of ribonuclear protein and release of viral nucleic acids into the cytoplasm (uncoating). Viral RNA replication occurs in the nucleus by the viral RNA polymerase (RNAp) complex. Following replication of viral RNA and synthesis of structural/nonstructural proteins, virions are assembled and released. Sites of action of antiviral compounds are shown by a solid line.

Citation: Pereira M, Miko B, Mehta M, Hammer S. 2017. Antirespiratory Virus Agents, p 271-290. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch14
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FIGURE 3

Schematic representation of the closed-state structure of the M2 protein channel by solid-state nuclear magnetic resonance (NMR) spectroscopy. Tetrameric assembly is shown from the side (A) and top (B). (Source: Nishimura K et al., 2002;13170–13177.) This image is cited as being in the public domain.

10.1128/9781555819439/9439ch14fig3_thmb.gif
10.1128/9781555819439/9439ch14fig3.gif
Image of FIGURE 3
FIGURE 3

Schematic representation of the closed-state structure of the M2 protein channel by solid-state nuclear magnetic resonance (NMR) spectroscopy. Tetrameric assembly is shown from the side (A) and top (B). (Source: Nishimura K et al., 2002;13170–13177.) This image is cited as being in the public domain.

Citation: Pereira M, Miko B, Mehta M, Hammer S. 2017. Antirespiratory Virus Agents, p 271-290. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch14
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FIGURE 4

Molecular structures of the neuraminidase inhibitors oseltamivir (A), zanamivir (B), and peramivir (C).

10.1128/9781555819439/9439ch14fig4_thmb.gif
10.1128/9781555819439/9439ch14fig4.gif
Image of FIGURE 4
FIGURE 4

Molecular structures of the neuraminidase inhibitors oseltamivir (A), zanamivir (B), and peramivir (C).

Citation: Pereira M, Miko B, Mehta M, Hammer S. 2017. Antirespiratory Virus Agents, p 271-290. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch14
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FIGURE 5

Molecular structure of ribavirin.

10.1128/9781555819439/9439ch14fig5_thmb.gif
10.1128/9781555819439/9439ch14fig5.gif
Image of FIGURE 5
FIGURE 5

Molecular structure of ribavirin.

Citation: Pereira M, Miko B, Mehta M, Hammer S. 2017. Antirespiratory Virus Agents, p 271-290. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch14
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References

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1. Koff WC, Elm JL Jr, Halstead SB . 1980. Inhibition of dengue virus replication by amantadine hydrochloride. Antimicrob Agents Chemother 18 : 125– 129.[PubMed]
2. Jing X, Ma C, Ohigashi Y, Oliveira FA, Jardetzky TS, Pinto LH, Lamb RA . 2008. Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel. Proc Natl Acad Sci USA 105 : 10967– 10972.[PubMed]
3. Ilyushina NA, Govorkova EA, Russell CJ, Hoffmann E, Webster RG . 2007. Contribution of H7 haemagglutinin to amantadine resistance and infectivity of influenza virus. J Gen Virol 88 : 1266– 1274.[PubMed]
4. Hayden FG, Aoki FY . 1998. Amantadine, Rimandatine and related agents, p 1344– 1365. In Antimocrobial Therapy and Vaccines, 2nd ed, vol II, Williams & Wilkins, Baltimore, MD.
5. Aoki FY, Sitar DS . 1988. Clinical pharmacokinetics of amantadine hydrochloride. Clin Pharmacokinet 14 : 35– 51.[PubMed]
6. Pandit PB, Chitayat D, Jefferies AL, Landes A, Qamar IU, Koren G . 1994. Tibial hemimelia and tetralogy of Fallot associated with first trimester exposure to amantadine. Reprod Toxicol 8 : 89– 92.[PubMed]
7. Oxford JS, Galbraith A . 1980. Antiviral activity of amantadine: a review of laboratory and clinical data. Pharmacol Ther 11 : 181– 262.[PubMed]
8. Belshe RB, Smith MH, Hall CB, Betts R, Hay AJ . 1988. Genetic basis of resistance to rimantadine emerging during treatment of influenza virus infection. J Virol 62 : 1508– 1512.[PubMed]
9. Hayden FG, Belshe RB, Clover RD, Hay AJ, Oakes MG, Soo W . 1989. Emergence and apparent transmission of rimantadine-resistant influenza A virus in families. N Engl J Med 321 : 1696– 1702.[PubMed]
10. Hayden FG, Pavia AT . 2006. Antiviral management of seasonal and pandemic influenza. J Infect Dis 194( Suppl 2) : S119– S126.[PubMed]
11. Saito R, Li D, Suzuki Y, Sato I, Masaki H, Nishimura H, Kawashima T, Shirahige Y, Shimomura C, Asoh N, Degawa S, Ishikawa H, Sato M, Shobugawa Y, Suzuki H . 2007. High prevalence of amantadine-resistance influenza a (H3N2) in six prefectures, Japan, in the 2005–2006 season. J Med Virol 79 : 1569– 1576.[PubMed]
12. Fiore AE, Fry A, Shay D, Gubareva L, Bresee JS, Uyeki TM Centers for Disease Control and Prevention (CDC) . 2011. Antiviral agents for the treatment and chemoprophylaxis of influenza—recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 60 : 1– 24.[PubMed]
13. CDC . 2016. Influenza Antiviral Medications: Summary for Clinicians. http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm. Accessed 4/22/2016.
14. Nguyen JT, Smee DF, Barnard DL, Julander JG, Gross M, de Jong MD, Went GT . 2012. Efficacy of combined therapy with amantadine, oseltamivir, and ribavirin in vivo against susceptible and amantadine-resistant influenza A viruses. PLoS One 7 : e31006.[PubMed]
15. Douglas RG Jr . 1990. Prophylaxis and treatment of influenza. N Engl J Med 322 : 443– 450.[PubMed]
16. Jefferson T, Demicheli V, Di Pietrantonj C, Rivetti D . 2006. Amantadine and rimantadine for influenza A in adults. Cochrane Database Syst Rev ( 2) : CD001169.[PubMed]
17. Anonymous . 1994. Rimantadine approved for treatment, prophylaxis of influenza A. Am J Hosp Pharm 51 : 16.[PubMed]
18. Valette M, Allard JP, Aymard M, Millet V . 1993. Susceptibilities to rimantadine of influenza A/H1N1 and A/H3N2 viruses isolated during the epidemics of 1988 to 1989 and 1989 to 1990. Antimicrob Agents Chemother 37 : 2239– 2240.[PubMed]
19. Koff WC, Elm JL Jr, Halstead SB . 1981. Suppression of dengue virus replication in vitro by rimantadine hydrochloride. Am J Trop Med Hyg 30 : 184– 189.[PubMed]
20. Wills RJ, Belshe R, Tomlinsin D, De Grazia F, Lin A, Wells S, Milazzo J, Berry C . 1987. Pharmacokinetics of rimantadine hydrochloride in patients with chronic liver disease. Clin Pharmacol Ther 42 : 449– 454.[PubMed]
21. Tominack RL, Wills RJ, Gustavson LE, Hayden FG . 1988. Multiple-dose pharmacokinetics of rimantadine in elderly adults. Antimicrob Agents Chemother 32 : 1813– 1819.[PubMed]
22. Wintermeyer SM, Nahata MC . 1995. Rimantadine: a clinical perspective. Ann Pharmacother 29 : 299– 310.[PubMed]
23. McKimm-Breschkin J, Trivedi T, Hampson A, Hay A, Klimov A, Tashiro M, Hayden F, Zambon M . 2003. Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir. Antimicrob Agents Chemother 47 : 2264– 2272.[PubMed]
24. Burnham AJ, Baranovich T, Govorkova EA . 2013. Neuraminidase inhibitors for influenza B virus infection: efficacy and resistance. Antiviral Res 100 : 520– 534.[PubMed]
25. Kim CU, Chen X, Mendel DB . 1999. Neuraminidase inhibitors as anti-influenza virus agents. Antivir Chem Chemother 10 : 141– 154.[PubMed]
26. Cass LM, Brown J, Pickford M, Fayinka S, Newman SP, Johansson CJ, Bye A . 1999. Pharmacoscintigraphic evaluation of lung deposition of inhaled zanamivir in healthy volunteers. Clin Pharmacokinet 36( Suppl 1) : 21– 31.[PubMed]
27. Peng AW, Milleri S, Stein DS . 2000. Direct measurement of the anti-influenza agent zanamivir in the respiratory tract following inhalation. Antimicrob Agents Chemother 44 : 1974– 1976.[PubMed]
28. Cass LM, Gunawardena KA, Macmahon MM, Bye A . 2000. Pulmonary function and airway responsiveness in mild to moderate asthmatics given repeated inhaled doses of zanamivir. Respir Med 94 : 166– 173.[PubMed]
29. Kiatboonsri S, Kiatboonsri C, Theerawit P . 2010. Fatal respiratory events caused by zanamivir nebulization. Clin Infect Dis 50 : 620.[PubMed]
30. Rasmussen SA, Jamieson DJ, Macfarlane K, Cragan JD, Williams J, Henderson Z . 2009. Pandemic influenza and pregnant women: summary of a meeting of experts. Am J Public Health 99( Suppl 2) : S248– S254.[PubMed]
31. Tanaka T, Nakajima K, Murashima A, Garcia-Bournissen F, Koren G, Ito S . 2009. Safety of neuraminidase inhibitors against novel influenza A (H1N1) in pregnant and breastfeeding women. CMAJ 181 : 55– 58.[PubMed]
32. Greer LG, Sheffield JS, Rogers VL, Roberts SW, McIntire DD, Wendel GD Jr . 2010. Maternal and neonatal outcomes after antepartum treatment of influenza with antiviral medications. Obstet Gynecol 115 : 711– 716.[PubMed]
33. Dunstan HJ, Mill AC, Stephens S, Yates LM, Thomas SH . 2014. Pregnancy outcome following maternal use of zanamivir or oseltamivir during the 2009 influenza A/H1N1 pandemic: a national prospective surveillance study. BJOG 121 : 901– 906.[PubMed]
34. Yen HL, Ilyushina NA, Salomon R, Hoffmann E, Webster RG, Govorkova EA . 2007. Neuraminidase inhibitor resistant recombinant A/Vietnam/1203/04 (H5N1) influenza viruses retain their replication efficiency and pathogenicity in vitro and in vivo. J Virol 81 : 12418– 12426.
35. Gubareva LV, Matrosovich MN, Brenner MK, Bethell RC, Webster RG . 1998. Evidence for zanamivir resistance in an immunocompromised child infected with influenza B virus. J Infect Dis 178 : 1257– 1262.[PubMed]
36. Ison MG, Gubareva LV, Atmar RL, Treanor J, Hayden FG . 2006. Recovery of drug-resistant influenza virus from immunocompromised patients: a case series. J Infect Dis 193 : 760– 764.[PubMed]
37. Hatakeyama S, Sugaya N, Ito M, Yamazaki M, Ichikawa M, Kimura K, Kiso M, Shimizu H, Kawakami C, Koike K, Mitamura K, Kawaoka Y . 2007. Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. JAMA 297 : 1435– 1442.[PubMed]
38. Monto AS, McKimm-Breschkin JL, Macken C, Hampson AW, Hay A, Klimov A, Tashiro M, Webster RG, Aymard M, Hayden FG, Zambon M . 2006. Detection of influenza viruses resistant to neuraminidase inhibitors in global surveillance during the first 3 years of their use. Antimicrob Agents Chemother 50 : 2395– 2402.[PubMed]
39. Thorlund K, Awad T, Boivin G, Thabane L . 2011. Systematic review of influenza resistance to the neuraminidase inhibitors. BMC Infect Dis 11 : 134.[PubMed]
40. Monto AS, Webster A, Keene O . 1999. Randomized, placebo-controlled studies of inhaled zanamivir in the treatment of influenza A and B: pooled efficacy analysis. J Antimicrob Chemother 44 Suppl B : 23– 29.
41. Hayden FG, Gubareva LV, Monto AS, Klein TC, Elliot MJ, Hammond JM, Sharp SJ, Ossi MJ for the Zanamivir Family Study Group . 2000. Inhaled zanamivir for the prevention of influenza in families. N Engl J Med 343 : 1282– 1289.[PubMed]
42. Lee C, Loeb M, Phillips A, Nesbitt J, Smith K, Fearon M, McArthur MA, Mazzulli T, Li Y, McGeer A . 2000. Zanamivir use during transmission of amantadine-resistant influenza A in a nursing home. Infect Control Hosp Epidemiol 21 : 700– 704.[PubMed]
43. Webster A, Boyce M, Edmundson S, Miller I . 1999. Coadministration of orally inhaled zanamivir with inactivated trivalent influenza vaccine does not adversely affect the production of antihaemagglutinin antibodies in the serum of healthy volunteers. Clin Pharmacokinet 36( Suppl 1) : 51– 58.[PubMed]
44. Ison MG, Gnann JW Jr, Nagy-Agren S, Treannor J, Paya C, Steigbigel R, Elliott M, Weiss HL, Hayden FG NIAID Collaborative Antiviral Study Group . 2003. Safety and efficacy of nebulized zanamivir in hospitalized patients with serious influenza. Antivir Ther 8 : 183– 190.[PubMed]
45. Da Dalt L, Calistri A, Chillemi C, Cusinato R, Franchin E, Salata C, Sgarabotto D, Toscano G, Gambino A, Palù G . 2010. Oseltamivir-resistant pandemic (H1N1) 2009 treated with nebulized zanamivir. Emerg Infect Dis 16 : 1813– 1815.[PubMed]
46. Schünemann HJ, Hill SR, Kakad M, Bellamy R, Uyeki TM, Hayden FG, Yazdanpanah Y, Beigel J, Chotpitayasunondh T, Del Mar C, Farrar J, Hein TT, Özbay B, Sugaya N, Fukuda K, Shindo N, Stockman L, Vist GE, Croisier A, Nagjdaliyev A, Roth C, Thomson G, Zucker H, Oxman AD for the WHO Rapid Advice Guideline Panel on Avian Influenza . 2007. WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus. Lancet Infect Dis 7 : 21– 31.[PubMed]
47. Marty FM, Man CY, van der Horst C, Francois B, Garot D, Mánez R, Thamlikitkul V, Lorente JA, Alvarez-Lerma F, Brealey D, Zhao HH, Weller S, Yates PJ, Peppercorn AF . 2014. Safety and pharmacokinetics of intravenous zanamivir treatment in hospitalized adults with influenza: an open-label, multicenter, single-arm, phase II study. J Infect Dis 209 : 542– 550.[PubMed]
48. GSK . 2016. Clinical Trial Register. http://www.gsk-clinicalstudyregister.com/study/114373#ps. Accessed 4/22/2016.
49. Anonymous . Personal communication with Genentech, Inc. April 2016 ed.
50. Boivin G, Goyette N . 2002. Susceptibility of recent Canadian influenza A and B virus isolates to different neuraminidase inhibitors. Antiviral Res 54 : 143– 147.[PubMed]
51. Gubareva LV, Webster RG, Hayden FG . 2001. Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants. Antimicrob Agents Chemother 45 : 3403– 3408.[PubMed]
52. Heinonen S, Silvennoinen H, Lehtinen P, Vainionpää R, Vahlberg T, Ziegler T, Ikonen N, Puhakka T, Heikkinen T . 2010. Early oseltamivir treatment of influenza in children 1–3 years of age: a randomized controlled trial. Clin Infect Dis 51 : 887– 894.[PubMed]
53. Moore ML, Chi MH, Zhou W, Goleniewska K, O'Neal JF, Higginbotham JN, Peebles RS Jr . 2007. Cutting edge: Oseltamivir decreases T cell GM1 expression and inhibits clearance of respiratory syncytial virus: potential role of endogenous sialidase in antiviral immunity. J Immunol 178 : 2651– 2654.[PubMed]
54. McCullers JA, Bartmess KC . 2003. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J Infect Dis 187 : 1000– 1009.[PubMed]
55. Eisenberg EJ, Bidgood A, Cundy KC . 1997. Penetration of GS4071, a novel influenza neuraminidase inhibitor, into rat bronchoalveolar lining fluid following oral administration of the prodrug GS4104. Antimicrob Agents Chemother 41 : 1949– 1952.[PubMed]
56. Jhee SS, Yen M, Ereshefsky L, Leibowitz M, Schulte M, Kaeser B, Boak L, Patel A, Hoffmann G, Prinssen EP, Rayner CR . 2008. Low penetration of oseltamivir and its carboxylate into cerebrospinal fluid in healthy Japanese and Caucasian volunteers. Antimicrob Agents Chemother 52 : 3687– 3693.[PubMed]
57. He G, Massarella J, Ward P . 1999. Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802. Clin Pharmacokinet 37 : 471– 484.[PubMed]
58. Snell P, Dave N, Wilson K, Rowell L, Weil A, Galitz L, Robson R . 2005. Lack of effect of moderate hepatic impairment on the pharmacokinetics of oral oseltamivir and its metabolite oseltamivir carboxylate. Br J Clin Pharmacol 59 : 598– 601. [Corrected in “ Br J Clin Pharmacol. 2005 Jul;60(1):115. Note: Dosage error in article text.][PubMed]
59. Smith JR, Rayner CR, Donner B, Wollenhaupt M, Klumpp K, Dutkowski R . 2011. Oseltamivir in seasonal, pandemic, and avian influenza: a comprehensive review of 10-years clinical experience. Adv Ther 28 : 927– 959.[PubMed]
60. Moscona A . 2005. Neuraminidase inhibitors for influenza. N Engl J Med 353 : 1363– 1373.[PubMed]
61. American Academy of Pediatrics Committee on Infectious Diseases . 2007. Antiviral therapy and prophylaxis for influenza in children. Pediatrics 119 : 852– 860.[PubMed]
62. Xie HY, Yasseen AS 3rd, Xie RH, Fell DB, Sprague AE, Liu N, Smith GN, Walker MC, Wen SW . 2013. Infant outcomes among pregnant women who used oseltamivir for treatment of influenza during the H1N1 epidemic. Am J Obstet Gynecol 208 : 293.e1– 293.e7.
63. Beau AB, Hurault-Delarue C, Vial T, Montastruc JL, Damase-Michel C, Lacroix I . 2014. Safety of oseltamivir during pregnancy: a comparative study using the EFEMERIS database. BJOG 121 : 895– 900.[PubMed]
64. Svensson T, Granath F, Stephansson O, Kieler H . 2011. Birth outcomes among women exposed to neuraminidase inhibitors during pregnancy. Pharmacoepidemiol Drug Saf 20 : 1030– 1034.[PubMed]
65. Greer LG, Leff RD, Rogers VL, Roberts SW, McCracken GH Jr, ., Wendel GD Jr., Sheffield JS . 2011. Pharmacokinetics of oseltamivir in breast milk and maternal plasma. Am J Obstet Gynecol 204 : 524-e1.
66. Shi D, Yang J, Yang D, LeCluyse EL, Black C, You L, Akhlaghi F, Yan B . 2006. Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. J Pharmacol Exp Ther 319 : 1477– 1484.[PubMed]
67. Reece PA . 2007. Neuraminidase inhibitor resistance in influenza viruses. J Med Virol 79 : 1577– 1586.[PubMed]
68. Rameix-Welti MA, Enouf V, Cuvelier F, Jeannin P, van der Werf S . 2008. Enzymatic properties of the neuraminidase of seasonal H1N1 influenza viruses provide insights for the emergence of natural resistance to oseltamivir. PLoS Pathog 4 : e1000103.[PubMed]
69. Bloom JD, Gong LI, Baltimore D . 2010. Permissive secondary mutations enable the evolution of influenza oseltamivir resistance. Science 328 : 1272– 1275.[PubMed]
70. Okomo-Adhiambo M, Fry AM, Su S, Nguyen HT, Elal AA, Negron E, Hand J, Garten RJ, Barnes J, Xiyan X, Villanueva JM, Gubareva LV 2013–14 US Influenza Antiviral Working Group . 2015. Oseltamivir-resistant influenza A(H1N1)pdm09 viruses, United States, 2013–14. Emerg Infect Dis 21 : 136– 141.[PubMed]
71. Hurt AC, Hardie K, Wilson NJ, Deng YM, Osbourn M, Leang SK, Lee RT, Iannello P, Gehrig N, Shaw R, Wark P, Caldwell N, Givney RC, Xue L, Maurer-Stroh S, Dwyer DE, Wang B, Smith DW, Levy A, Booy R, Dixit R, Merritt T, Kelso A, Dalton C, Durrheim D, Barr IG . 2012. Characteristics of a widespread community cluster of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza in Australia. J Infect Dis 206 : 148– 157.[PubMed]
72. Meijer A, Jonges M, van Beek P, Swaan CM, Osterhaus AD, Daniels RS, Hurt AC, Koopmans MP . 2012. Oseltamivir-resistant influenza A(H1N1)pdm09 virus in Dutch travellers returning from Spain, August 2012. Euro Surveill 17 : 20266.[PubMed]
73. Butler J, Hooper KA, Petrie S, Lee R, Maurer-Stroh S, Reh L, Guarnaccia T, Baas C, Xue L, Vitesnik S, Leang SK, McVernon J, Kelso A, Barr IG, McCaw JM, Bloom JD, Hurt AC . 2014. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1)pdm09 influenza viruses. PLoS Pathog 10 : e1004065.[PubMed]
74. Whitley RJ, Boucher CA, Lina B, Nguyen-Van-Tam JS, Osterhaus A, Schutten M, Monto AS . 2013. Global assessment of resistance to neuraminidase inhibitors, 2008–2011: the Influenza Resistance Information Study (IRIS). Clin Infect Dis 56 : 1197– 1205.[PubMed]
75. Boivin G . 2013. Detection and management of antiviral resistance for influenza viruses. Influenza Other Respi Viruses 7( Suppl 3) : 18– 23.[PubMed]
76. de Jong MD, Thanh TT, Khanh TH, Hien VM, Smith GJD, Chau NV, Cam BV, Qui PT, Ha DQ, Guan Y, Peiris JSM, Hien TT, Farrar J . 2005. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 353 : 2667– 2672.[PubMed]
77. Hu Y, Lu S, Song Z, Wang W, Hao P, Li J, Zhang X, Yen HL, Shi B, Li T, Guan W, Xu L, Liu Y, Wang S, Zhang X, Tian D, Zhu Z, He J, Huang K, Chen H, Zheng L, Li X, Ping J, Kang B, Xi X, Zha L, Li Y, Zhang Z, Peiris M, Yuan Z . 2013. Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet 381 : 2273– 2279.[PubMed]
78. Fry AM, Goswami D, Nahar K, Sharmin AT, Rahman M, Gubareva L, Azim T, Bresee J, Luby SP, Brooks WA . 2014. Efficacy of oseltamivir treatment started within 5 days of symptom onset to reduce influenza illness duration and virus shedding in an urban setting in Bangladesh: a randomised placebo-controlled trial. Lancet Infect Dis 14 : 109– 118.[PubMed]
79. Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D, Mills RG, Ward P . 2001. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 20 : 127– 133.[PubMed]
80. Muthuri SG, Myles PR, Venkatesan S, Leonardi-Bee J, Nguyen-Van-Tam JS . 2013. Impact of neuraminidase inhibitor treatment on outcomes of public health importance during the 2009–2010 influenza A(H1N1) pandemic: a systematic review and meta-analysis in hospitalized patients. J Infect Dis 207 : 553– 563.[PubMed]
81. Muthuri SG . , et al PRIDE Consortium Investigators . 2014. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med 2 : 395– 404.[PubMed]
82. Louie JK, Yang S, Samuel MC, Uyeki TM, Schechter R . 2013. Neuraminidase inhibitors for critically ill children with influenza. Pediatrics 132 : e1539– e1545.
83. Li IW, Hung IF, To KK, Chan KH, Wong SS, Chan JF, Cheng VC, Tsang OT, Lai ST, Lau YL, Yuen KY . 2010. The natural viral load profile of patients with pandemic 2009 influenza A(H1N1) and the effect of oseltamivir treatment. Chest 137 : 759– 768.[PubMed]
84. Cao B, Li XW, Mao Y, Wang J, Lu HZ, Chen YS, Liang ZA, Liang L, Zhang SJ, Zhang B, Gu L, Lu LH, Wang DY, Wang C National Influenza A Pandemic (H1N1) 2009 Clinical Investigation Group of China . 2009. Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China. N Engl J Med 361 : 2507– 2517.[PubMed]
85. Ling LM, Chow AL, Lye DC, Tan AS, Krishnan P, Cui L, Win NN, Chan M, Lim PL, Lee CC, Leo YS . 2010. Effects of early oseltamivir therapy on viral shedding in 2009 pandemic influenza A (H1N1) virus infection. Clin Infect Dis 50 : 963– 969.[PubMed]
86. Lee N, Hui DS, Zuo Z, Ngai KL, Lui GC, Wo SK, Tam WW, Chan MC, Wong BC, Wong RY, Choi KW, Sin WW, Lee EL, Tomlinson B, Hayden FG, Chan PK . 2013. A prospective intervention study on higher-dose oseltamivir treatment in adults hospitalized with influenza a and B infections. Clin Infect Dis 57 : 1511– 1519.[PubMed]
87. Abdel-Ghafar AN, Chotpitayasunondh T, Gao Z, Hayden FG, Nguyen DH, de Jong MD, Naghdaliyev A, Peiris JS, Shindo N, Soeroso S, Uyeki TM Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus . 2008. Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med 358 : 261– 273.[PubMed]
88. Welliver R, Monto AS, Carewicz O, Schatteman E, Hassman M, Hedrick J, Jackson HC, Huson L, Ward P, Oxford JS . 2001. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. JAMA 285 : 748– 54.
89. Peters PH Jr, Gravenstein S, Norwood P, De Bock V, Van Couter A, Gibbens M, von Planta TA, Ward P . 2001. Long-term use of oseltamivir for the prophylaxis of influenza in a vaccinated frail older population. J Am Geriatr Soc 49 : 1025– 1031.[PubMed]
90. Hayden FG, Atmar RL, Schilling M, Johnson C, Poretz D, Paar D, Huson L, Ward P, Mills RG . 1999. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med 341 : 1336– 1343.[PubMed]
91. Birnkrant D, Cox E . 2009. The Emergency Use Authorization of peramivir for treatment of 2009 H1N1 influenza. N Engl J Med 361 : 2204– 2207.[PubMed]
92. Yu Y, Garg S, Yu PA, Kim HJ, Patel A, Merlin T, Redd S, Uyeki TM . 2012. Peramivir use for treatment of hospitalized patients with influenza A(H1N1)pdm09 under emergency use authorization, October 2009-June 2010. Clin Infect Dis 55 : 8– 15.[PubMed]
93. Louie JK, Yang S, Yen C, Acosta M, Schechter R, Uyeki TM . 2012. Use of intravenous peramivir for treatment of severe influenza A(H1N1)pdm09. PLoS One 7 : e40261.[PubMed]
94. de Jong MD, Ison MG, Monto AS, Metev H, Clark C, O'Neil B, Elder J, McCullough A, Collis P, Sheridan WP . 2014. Evaluation of intravenous peramivir for treatment of influenza in hospitalized patients. Clin Infect Dis 59 : e172– e185.[PubMed]
95. Anonymous . Rapivab®. [package insert] Durham, NC: BioCryst Pharmaceuticals Inc; 2014.
96. Kohno S, Kida H, Mizuguchi M, Shimada J for the S-021812 Clinical Study Group . 2010. Efficacy and safety of intravenous peramivir for treatment of seasonal influenza virus infection. Antimicrob Agents Chemother 54 : 4568– 4574.[PubMed]
97. Matsuo Y, Ishibashi T, Hollister AS, Wajima T . 2015. Population pharmacokinetics of peramivir in healthy volunteers and influenza patients. Antimicrob Agents Chemother 59 : 6755– 6762.[PubMed]
98. Chairat K, Tarning J, White NJ, Lindegardh N . 2013. Pharmacokinetic properties of anti-influenza neuraminidase inhibitors. J Clin Pharmacol 53 : 119– 139.[PubMed]
99. Harada-Shirado K, Ikeda K, Furukawa M, Sukegawa M, Takahashi H, Shichishima-Nakamura A, Ohkawara H, Noji H, Kawabata K, Saito S, Ohto H, Ogawa K, Takeishi Y . 2014. Severe immune thrombocytopenia possibly elicited by the anti-influenza viral agent peramivir. Intern Med 53 : 2369– 2371.[PubMed]
100. Hayashi K, Iwasa K, Morinaga A, Ono K, Yamada M . 2015. Exacerbation of myasthenia gravis by intravenous peramivir. Muscle Nerve 51 : 935– 936.[PubMed]
101. Takashita E, Ejima M, Itoh R, Miura M, Ohnishi A, Nishimura H, Odagiri T, Tashiro M . 2014. A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance to oseltamivir and peramivir in Japan, November to December 2013. Euro Surveill 19 : 20666.[PubMed]
102. Renaud C, Pergam SA, Polyak C, Jain R, Kuypers J, Englund JA, Corey L, Boeckh MJ . 2010. Early emergence of an H275Y mutation in a hematopoietic cell transplant recipient treated with intravenous peramivir. Transpl Infect Dis 12 : 513– 517.[PubMed]
103. Whitley R, Laughlin A, Carson S, Mitha E, Tellier G, Stich M, Elder J, Alexander WJ, Dobo S, Collis P, Sheridan WP . 2015. Single dose peramivir for the treatment of acute seasonal influenza: integrated analysis of efficacy and safety from two placebo-controlled trials. Antivir Ther 20 : 709– 719.[PubMed]
104. Pharmaceuticals B . A Phase II, Multicenter, Randomized, Placebo-Controlled, Study to Evaluate the Efficacy and Safety of Intramuscular Peramivir 600 mg in Subjects With Uncomplicated Acute Influenza. https://clinicaltrials.gov/ct2/show/NCT00705406?term=NCT00705406&rank=1. Accessed on 4/22/2016
105. Alame MM, Massaad E, Zaraket H . 2016. Peramivir: a novel intravenous neuraminidase inhibitor for treatment of acute influenza infections. Front Microbiol 7 : 450.[PubMed]
106. Kohno S, Yen MY, Cheong HJ, Hirotsu N, Ishida T, Kadota J, Mizuguchi M, Kida H, Shimada J for the S-021812 Clinical Study Group . 2011. Phase III randomized, double-blind study comparing single-dose intravenous peramivir with oral oseltamivir in patients with seasonal influenza virus infection. Antimicrob Agents Chemother 55 : 5267– 5276.[PubMed]
107. Ison MG, Hui DS, Clezy K, O'Neil BJ, Flynt A, Collis PJ, Simon TJ, Alexander WJ . 2013. A clinical trial of intravenous peramivir compared with oral oseltamivir for the treatment of seasonal influenza in hospitalized adults. Antivir Ther 18 : 651– 661.[PubMed]
108. The IMpact-RSV Study Group . 1998. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 102 : 531– 537.
109. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM, Johnson DW, Light MJ, Maraqa NF, Mendonca EA, Phelan KJ. 2014. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics 134: e1474– e1502. Pediatrics 136 : 782.[PubMed]
110. Chen JJ, Chan P, Paes B, Mitchell I, Li A, Lanctôt KL CARESS Investigators . 2015. Serious adverse events in the Canadian Registry of children receiving palivizumab (CARESS) for respiratory syncytial virus prevention. PLoS One 10 : e0134711.[PubMed]
111. Krilov LR . 2002. Safety issues related to the administration of ribavirin. Pediatr Infect Dis J 21 : 479– 481.[PubMed]
112. Kilham L, Ferm VH . 1977. Congenital anomalies induced in hamster embryos with ribavirin. Science 195 : 413– 414.[PubMed]
113. Carmack MA, Prober CG, . 1995. Respiratory syncytial virus: antiviral therapy, p 357– 390. In Jeffries DJ, DeClerq E (ed), Antiviral Chemotherapy. John Wiley & Sons, Ltd, Chichester, United Kingdom.
114. Chemaly RF, Shah DP, Boeckh MJ . 2014. Management of respiratory viral infections in hematopoietic cell transplant recipients and patients with hematologic malignancies. Clin Infect Dis 59( Suppl 5) : S344– S351.[PubMed]
115. Casey J, Morris K, Narayana M, Nakagaki M, Kennedy GA . 2013. Oral ribavirin for treatment of respiratory syncitial virus and parainfluenza 3 virus infections post allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant 48 : 1558– 1561.[PubMed]
116. Kim WY, Young Suh G, Huh JW, Kim SH, Kim MJ, Kim YS, Kim HR, Ryu YJ, Han MS, Ko YG, Chon GR, Lee KH, Choi SH, Hong SB Korean Society of Critical Care Medicine H1N1 Collaborative . 2011. Triple-combination antiviral drug for pandemic H1N1 influenza virus infection in critically ill patients on mechanical ventilation. Antimicrob Agents Chemother 55 : 5703– 5709.[PubMed]
117. Seo S, Englund JA, Nguyen JT, Pukrittayakamee S, Lindegardh N, Tarning J, Tambyah PA, Renaud C, Went GT, de Jong MD, Boeckh MJ . 2013. Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: safety and pharmacokinetics. Antivir Ther 18 : 377– 386.[PubMed]
118. Raza K, Ismailjee SB, Crespo M, Studer SM, Sanghavi S, Paterson DL, Kwak EJ, Rinaldo CR Jr, Pilewski JM, McCurry KR, Husain S . 2007. Successful outcome of human metapneumovirus (hMPV) pneumonia in a lung transplant recipient treated with intravenous ribavirin. J Heart Lung Transplant 26 : 862– 864.[PubMed]
119. Stockman LJ, Bellamy R, Garner P . 2006. SARS: systematic review of treatment effects. PLoS Med 3 : e343.[PubMed]
120. Barnard DL, Day CW, Bailey K, Heiner M, Montgomery R, Lauridsen L, Winslow S, Hoopes J, Li JK, Lee J, Carson DA, Cottam HB, Sidwell RW . 2006. Enhancement of the infectivity of SARS-CoV in BALB/c mice by IMP dehydrogenase inhibitors, including ribavirin. Antiviral Res 71 : 53– 63.[PubMed]
121. Al-Tawfiq JA, Momattin H, Dib J, Memish ZA . 2014. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study. Int J Infect Dis 20 : 42– 46.[PubMed]
122. Omrani AS, Saad MM, Baig K, Bahloul A, Abdul-Matin M, Alaidaroos AY, Almakhlafi GA, Albarrak MM, Memish ZA, Albarrak AM . 2014. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis 14 : 1090– 1095.[PubMed]
123. Shalhoub S, Farahat F, Al-Jiffri A, Simhairi R, Shamma O, Siddiqi N, Mushtaq A . 2015. IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother 70 : 2129– 2132.[PubMed]
124. Boltz DA, Aldridge JR Jr, Webster RG, Govorkova EA . 2010. Drugs in development for influenza. Drugs 70 : 1349– 1362.[PubMed]
125. Furuta Y, Takahashi K, Kuno-Maekawa M, Sangawa H, Uehara S, Kozaki K, Nomura N, Egawa H, Shiraki K . 2005. Mechanism of action of T-705 against influenza virus. Antimicrob Agents Chemother 49 : 981– 986.[PubMed]
126. McKimm-Breschkin JL, Fry AM . 2016. Meeting report: 4th ISIRV antiviral group conference: novel antiviral therapies for influenza and other respiratory viruses. Antiviral Res 129 : 21– 38.[PubMed]
127. Byrn RA, Jones SM, Bennett HB, Bral C, Clark MP, Jacobs MD, Kwong AD, Ledeboer MW, Leeman JR, McNeil CF, Murcko MA, Nezami A, Perola E, Rijnbrand R, Saxena K, Tsai AW, Zhou Y, Charifson PS . 2015. Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit. Antimicrob Agents Chemother 59 : 1569– 1582.[PubMed]
128. Watanabe A, Chang SC, Kim MJ, Chu DW, Ohashi Y MARVEL Study Group . 2010. Long-acting neuraminidase inhibitor laninamivir octanoate versus oseltamivir for treatment of influenza: a double-blind, randomized, noninferiority clinical trial. Clin Infect Dis 51 : 1167– 1175.[PubMed]
129. Anonymous . 2014. Biota reports reports top-line line data from its Phase 2 “IGLOO” trial of laninamivir octanoate. http://investors.aviragentherapeutics.com/releasedetail.cfm?releaseid=863626. Accessed 4/21/2016.
130. Haffizulla J, Hartman A, Hoppers M, Resnick H, Samudrala S, Ginocchio C, Bardin M, Rossignol JF US Nitazoxanide Influenza Clinical Study Group . 2014. Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial. Lancet Infect Dis 14 : 609– 618.[PubMed]
131. Belardo G, Cenciarelli O, La Frazia S, Rossignol JF, Santoro MG . 2015. Synergistic effect of nitazoxanide with neuraminidase inhibitors against influenza A viruses in vitro. Antimicrob Agents Chemother 59 : 1061– 1069.[PubMed]
132. Rossignol JF . 2014. Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral Res 110 : 94– 103.[PubMed]
133. DeVincenzo JP, Whitley RJ, Mackman RL, Scaglioni-Weinlich C, Harrison L, Farrell E, McBride S, Lambkin-Williams R, Jordan R, Xin Y, Ramanathan S, O'Riordan T, Lewis SA, Li X, Toback SL, Lin SL, Chien JW . 2014. Oral GS-5806 activity in a respiratory syncytial virus challenge study. N Engl J Med 371 : 711– 722.[PubMed]
134. Patel K, Kirkpatrick C, Nieforth K, Chanda S, Zhang Q, Mcclure M, Fry J, Symons J, Blatt L, Beigelman L, Smith P . Population PK/PD modeling of human respiratory syncytial virus infection and the antiviral effect of AL-8176 - Poster 807, presented in IDWeek 2015 San Diego, CA.
135. Hong J,, Liu H, Taylor J, Mcclure M, Chanda S, Fry J, Beigelman L, Blatt L, Symons J . The anti-respiratory syncytial virus (RSV) nucleoside analog, AL-8112, and its orally bioavailable prodrug, AL-8176, exhibit a high barrier to the emergence of viral resistance—Poster 1188, presented in IDWeek 2015, San Diego, CA.
136. DeVincenzo JP, McClure MW, Symons JA, Fathi H, Westland C, Chanda S, Lambkin-Williams R, Smith P, Zhang Q, Beigelman L, Blatt LM, Fry J . 2015. Activity of oral ALS-008176 in a respiratory syncytial virus challenge study. N Engl J Med 373 : 2048– 2058.[PubMed]
137. Zenilman JM, Fuchs EJ, Hendrix CW, Radebaugh C, Jurao R, Nayak SU, Hamilton RG, McLeod Griffiss J . 2015. Phase 1 clinical trials of DAS181, an inhaled sialidase, in healthy adults. Antiviral Res 123 : 114– 119.[PubMed]
138. Waghmare A, Wagner T, Andrews R, Smith S, Kuypers J, Boeckh M, Moss R, Englund JA . 2015. Successful treatment of parainfluenza virus respiratory tract infection with DAS181 in 4 immunocompromised children. J Pediatric Infect Dis Soc 4 : 114– 118.[PubMed]
139. Florescu DF, Pergam SA, Neely MN, Qiu F, Johnston C, Way S, Sande J, Lewinsohn DA, Guzman-Cottrill JA, Graham ML, Papanicolaou G, Kurtzberg J, Rigdon J, Painter W, Mommeja-Marin H, Lanier R, Anderson M, van der Horst C . 2012. Safety and efficacy of CMX001 as salvage therapy for severe adenovirus infections in immunocompromised patients. Biol Blood Marrow Transplant 18 : 731– 738.[PubMed]
140. Anonymous . 2015. Biota Commences Dosing in Vapendavir SPIRITUS Phase 2b Trial. http://investors.aviragentherapeutics.com/releasedetail.cfm?ReleaseID=899451. Accessed 4/21/2016.
141. Djukanović R, Harrison T, Johnston SL, Gabbay F, Wark P, Thomson NC, Niven R, Singh D, Reddel HK, Davies DE, Marsden R, Boxall C, Dudley S, Plagnol V, Holgate ST, Monk P INTERCIA Study Group . 2014. The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. A randomized trial. Am J Respir Crit Care Med 190 : 145– 154.[PubMed]
142. Gottlieb J, Zamora MR, Hodges T, Musk AW, Sommerwerk U, Dilling D, Arcasoy S, DeVincenzo J, Karsten V, Shah S, Bettencourt BR, Cehelsky J, Nochur S, Gollob J, Vaishnaw A, Simon AR, Glanville AR . 2016. ALN-RSV01 for prevention of bronchiolitis obliterans syndrome after respiratory syncytial virus infection in lung transplant recipients. J Heart Lung Transplant 35 : 213– 221.[PubMed]
143. DeVincenzo J, Lambkin-Williams R, Wilkinson T, Cehelsky J, Nochur S, Walsh E, Meyers R, Gollob J, Vaishnaw A . 2010. A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus. Proc Natl Acad Sci USA 107 : 8800– 8805.[PubMed]
144. Warren TK . , et al . 2016. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature 531 : 381– 385.[PubMed]
145. Baranovich T, Jones JC, Russier M, Vogel P, Szretter KJ, Sloan SE, Seiler P, Trevejo JM, Webby RJ, Govorkova EA . 2016. The hemagglutinin stem-binding monoclonal antibody VIS410 controls influenza virus-induced acute respiratory distress syndrome. Antimicrob Agents Chemother 60 : 2118– 2131.[PubMed]
146. Tharakaraman K, Subramanian V, Viswanathan K, Sloan S, Yen HL, Barnard DL, Leung YH, Szretter KJ, Koch TJ, Delaney JC, Babcock GJ, Wogan GN, Sasisekharan R, Shriver Z . 2015. A broadly neutralizing human monoclonal antibody is effective against H7N9. Proc Natl Acad Sci USA 112 : 10890– 10895.[PubMed]
147. Wollacott AM, Boni MF, Szretter KJ, Sloan SE, Yousofshahi M, Viswanathan K, Bedard S, Hay CA, Smith PF, Shriver Z, Trevejo JM . 2016. Safety and upper respiratory pharmacokinetics of the hemagglutinin stalk-binding antibody VIS410 support treatment and prophylaxis based on population modeling of seasonal influenza A outbreaks. EBioMedicine 5 : 147– 155.[PubMed]
148. Gupta P, Kamath AV, Park S, Chiu H, Lutman J, Maia M, Tan MW, Xu M, Swem L, Deng R . 2016. Preclinical pharmacokinetics of MHAA4549A, a human monoclonal antibody to influenza A virus, and the prediction of its efficacious clinical dose for the treatment of patients hospitalized with influenza A. MAbs 1– 7.[PubMed]
149. Griffin MP, Khan AA, Jensen M, Takas TF, Dubovsky F, Robbie GJ . A passive vaccine Approach to RSV Prophylaxis for All Infants: Results of a Phase 1 Study in Healthy Adult Volunteers—Poster 549, presented in IDWeek 2015, San Diego, CA.
150. Sivapalasingam S, Caballero-Perez D, Houghton M, Yang F, Davis J, Gao B, Geba G . A phase 1 study evaluating safety, tolerability, pharmacokinetics and immunogenicity of REGN2222 in healthy adults: a new human monoclonal RSV- F antibody for RSV prevention—Poster 912, presented in IDWeek 2015, San Diego, CA.
151. Luke T, Wu H, Zhao J, Channappanavar R, Coleman CM, Jiao JA, Matsushita H, Liu Y, Postnikova EN, Ork BL, Glenn G, Flyer D, Defang G, Raviprakash K, Kochel T, Wang J, Nie W, Smith G, Hensley LE, Olinger GG, Kuhn JH, Holbrook MR, Johnson RF, Perlman S, Sullivan E, Frieman MB . 2016. Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. Sci Transl Med 8 : 326ra21.[PubMed]
152. Sui J, Deming M,