By Manoj C. Desai, Nicholas A. Meanwell, David E Thurston, Robin Ganellin, David Fox, Salvatore Guccione, Ana Martinez, David Rotella, Makonen Belema, David Sperandio, Pei-Yong Shi, Robert Jordan, Randall Halcomb, Christopher Roberts, Brian A Johns, Stephen
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Additional resources for Successful Strategies for the Discovery of Antiviral Drugs
A. James, R. Lavoie, O. D. Lopez, A. Martel, N. A. Meanwell, V. N. Nguyen, J. L. Romine, E. H. Ruediger, L. B. Snyder, D. R. St. Laurent, F. Yang, D. R. Langley, G. Wang and L. G. Hamann, Patent Application, WO2009–102568, 2009. 33. H. Guo, D. Kato, T. A. Kirschberg, H. Liu, J. O. Link, M. L. Mitchell, J. P. Parrish, N. Squires, J. Sun, J. Taylor, E. M. Bacon, E. Canales, A. Cho, J. J. Cottell, M. C. Desai, R. L. Halcomb, E. S. Krygowski, S. E. Lazerwith, Q. Liu, R. -J. Pyun, J. H. Saugier, J. D.
Another common preclinical challenge is the availability of relevant animal models to study the eﬀectiveness of RSV inhibitors in vivo. 15–17 These models, however, are not ideal since neither represents clinical disease in humans and, as such, the models are of limited use. 15,18–24 In the latter, bovine RSV is a common ailment of calves and livestock during the winter months. The course of infection in calves is very similar to that of infant disease and, therefore, represents a potential model in late-stage optimization of compounds.
65 For two additional patients, Q30E and Y93N variants were detected at day 14, a double mutant associated with high resistance to the drug. 76 The primary eﬃcacy endpoint focused on an extended virological response (eRVR), which is deﬁned as undetectable levels of viral RNA at both weeks 4 and 12 after initiation of therapy. 1 Chapter 1 Clinical results in a Phase 2a study of daclatasvir (1) combined with PEG-IFN/RBV. Assessmentsa Placebo (n ¼ 12)b 3 mg (n ¼ 12) 10 mg (n ¼ 12) 60 mg (n ¼ 12) RVR eRVR cEVR SVR12 SVR24 Virological failure 1 1 5 3 3 9 5 5 7 5 5 7 11 10 10 11 10 2 10 9 10 10 10 2 (8%) (8%) (42%) (25%) (25%) (75%) (42%) (42%) (58%) (42%) (42%) (58%) (92%) (83%) (83%) (92%) (83%) (17%) (83%) (75%) (83%) (83%) (83%) (17%) a RVR, viral RNA undetectable at 4 weeks; eRVR, viral RNA undetectable at both 4 and 12 weeks; cEVR, RNA undetectable at 12 weeks; SVRx, sustained virological response at x weeks after end of therapy.
Successful Strategies for the Discovery of Antiviral Drugs by Manoj C. Desai, Nicholas A. Meanwell, David E Thurston, Robin Ganellin, David Fox, Salvatore Guccione, Ana Martinez, David Rotella, Makonen Belema, David Sperandio, Pei-Yong Shi, Robert Jordan, Randall Halcomb, Christopher Roberts, Brian A Johns, Stephen