Appendix A.docx

Participant questionnaire on (A) confidence in language abilities (done pre and post-participation) and (B) familiarity/interest in iPad use (done only post-participation).<br><br>This figure supports a recent submission to Topics in Stroke Rehabilitatio

Discovery of an Oral Respiratory Syncytial Virus (RSV) Fusion Inhibitor (GS-5806) and Clinical Proof of Concept in a Human RSV Challenge Study

GS-5806 is a novel, orally bioavailable RSV fusion inhibitor discovered following a lead optimization campaign on a screening hit. The oral absorption properties were optimized by converting to the pyrazolo­[1,5-<i>a</i>]-pyrimidine heterocycle, while potency, metabolic, and physicochemical properties were optimized by introducing the <i>para</i>-chloro and aminopyrrolidine groups. A mean EC₅₀ = 0.43 nM was found toward a panel of 75 RSV A and B clinical isolates and dose-dependent antiviral efficacy in the cotton rat model of RSV infection. Oral bioavailability in preclinical species ranged from 46 to 100%, with evidence of efficient penetration into lung tissue. In healthy human volunteers experimentally infected with RSV, a potent antiviral effect was observed with a mean 4.2 log₁₀ reduction in peak viral load and a significant reduction in disease severity compared to placebo. In conclusion, a potent, once daily, oral RSV fusion inhibitor with the potential to treat RSV infection in infants and adults is reported