GS-441524 is a nucleoside analogue with broad-spectrum antiviral activity against RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and feline coronavirus (FCoV). GS-441524 is the main circulating metabolite following intravenous administration of remdesivir (Veklury®), with a plasma half-life of approximately 24 hours. The safety, tolerability, and pharmacokinetics of GS-441524 was evaluated in a healthy human volunteer (N=1) when administered directly as an oral solution (750 mg) once daily for 7 days (Part 1) and 3 times daily for 3 days (Part 2). In Part 1 of the study, the effect of food on the absorption of GS-441524 was also evaluated. GS-441524 appeared rapidly in plasma, with an average time of maximum concentration of 0.5 hours during once-per-day dosing and exhibited an initial half-life phase of approximately 3.3 hours in the fasted state. Negligible accumulation was observed during part 1 of the multiday study. In Part 2 of the study, GS-441524 was administered 3 times daily, every 3 hours. A 2-4-fold accumulation of GS-441524 was observed approximately 3 hours after the third dose was administered, with a time of maximum concentration of 9 hours and a maximum concentration of 12.01 µM, exceeding the concentration reported to eradicate SARS-CoV-2 in vitro. For the duration of the study, GS-441524 was well-tolerated. There were no treatment-related adverse events and no clinically significant findings in clinical laboratory, vital signs, or electrocardiography. Taken together, these results demonstrate the safety and viability of orally administered GS-441524 for the treatment of COVID-19 and emerging viral infections.
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