Inhalation efficacy of RFI‐641 in an African green monkey model of RSV infection

Weiss, Jason; Murphy, Timothy D.; Lynch, Maryellen; Frye, Joyce; Buklan, Aron; Gray, Barry M.; Lenoy, E.; Mitelman, S. L.; O’Connell, John F.; Quartuccio, S.; Huntley, Clayton C.

doi:10.1034/j.1600-0684.2003.00014.x

Cited by 38 publications

(18 citation statements)

References 18 publications

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“…As for the other RSV inhibitors, BABIM was reported to have antiviral activity in cotton rats after intraperitoneal administration (63), and R-170591 demonstrated efficacy in vivo after aerosol delivery in rodent models of RSV infection (Andries et al, 40th ICAAC). The efficacy of RFI-641 was shown in three models of RSV infection, but only when it was administered via the intranasal or aerosol route (27,66).…”

Section: Discussionmentioning

confidence: 99%

Orally Active Fusion Inhibitor of Respiratory Syncytial Virus

Cianci

Combrink

et al. 2004

Antimicrob Agents Chemother

128

116

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Respiratory syncytial virus (RSV) belongs to the Pneumovirus genus of the Paramyxovirus virus family. RSV is the leading cause of virus-induced lower respiratory tract disease among infants and children (6,21,26) and is the most common pathogen found in children under 5 years of age admitted to the hospital. Essentially every child develops an RSV infection during the first 2 years of life, and recurrent infections are common (20,24,42,44). RSV is especially serious in premature infants and children with bronchopulmonary dysplasia or congenital heart disease. Additionally, in recent studies, RSV was the most common virus identified in the middle-ear fluid of children suffering from acute otitis media (25,43). RSV infection has also been implicated in the development of childhood asthma and other long-term conditions involving pulmonary dysfunction (54-56).

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Section: Discussionmentioning

confidence: 99%

Orally Active Fusion Inhibitor of Respiratory Syncytial Virus

Cianci

Combrink

et al. 2004

Antimicrob Agents Chemother

128

116

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“…Multiple routes of administration are conceivable for these drug-like molecules, and highly cost-effective production strategies can be easily achieved. Additional conceptual support for this approach comes from the previous identification of small molecules that interfere with respiratory syncytial virus entry in vitro (2) and in vivo (2,35).…”

mentioning

confidence: 99%

Design of a Small-Molecule Entry Inhibitor with Activity against Primary Measles Virus Strains

Plemper

Doyle

Sun

et al. 2005

Antimicrob Agents Chemother

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The incidence of measles virus (MV) infection has been significantly reduced in many nations through extensive vaccination; however, the virus still causes significant morbidity and mortality in developing countries. Measles outbreaks also occur in some developed countries that have failed to maintain high vaccine coverage rates. While vaccination is essential in preventing the spread of measles, case management would greatly benefit from the use of therapeutic agents to lower morbidity. Thus, the development of new therapeutic strategies is desirable. We previously reported the generation of a panel of small-molecule MV entry inhibitors. Here we show that our initial lead compound, although providing proof of concept for our approach, has a short half-life (<16 h) under physiological conditions. In order to combine potent antiviral activity with increased compound stability, a targeted library of candidate molecules designed on the structural basis of the first lead has been synthesized and tested against MV. We have identified an improved lead with low toxicity and high stability (half-life Ͼ Ͼ 16 h) that prevents viral entry and hence infection. This compound shows high MV specificity and strong activity (50% inhibitory concentration ‫؍‬ 0.6 to 3.0 M, depending on the MV genotype) against a panel of wild-type MV strains representative of viruses that are currently endemic in the field.

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“…RFI-641 was shown to inhibit fusion and to interact directly with the RSV F protein (Razinkov et al, 2002). The in vivo potency of RFI-641 was evaluated in different animal model systems Weiss et al, 2003). RFI-641 administered intravenously did not exhibited efficacy in vivo, and therefore, this route of administration was not pursued.…”

Section: Entry Inhibitorsmentioning

confidence: 99%