GS-441524, the parent nucleoside of remdesivir, has been proposed to be effective against Covid-19 based on in vitro studies and studies in animals. However, randomized clinical trials of the agent to treat Covid-19 have not been conducted. Here, we evaluated GS-441524 for Covid-19 treatment based on studies reporting pharmacokinetic parameters of the agent in mice, rats, cats, dogs, monkeys, and the single individual in the first-in-human trial supplemented with information about its activity against severe acute respiratory syndrome coronavirus 2 and safety. A dosing interval of 8 h was considered clinically relevant and used to calculate steady-state plasma concentrations of GS-441524. These ranged from 0.27 to 234.41 μM, reflecting differences in species, doses, and administration routes. Fifty percent maximal inhibitory concentrations of GS-441524 against severe acute respiratory syndrome coronavirus 2 ranged from 0.08 μM to above 10 μM with a median of 0.87 μM whereas concentrations required to produce 90% of the maximal inhibition of the virus varied from 0.18 µM to more than 20 µM with a median of 1.42 µM in the collected data. Most of these concentrations were substantially lower than the calculated steady-state plasma concentrations of the agent. Plasma exposures to orally administered GS-441524, calculated after normalization of doses, were larger for dogs, mice, and rats than cynomolgus monkeys and humans, probably reflecting interspecies differences in oral uptake with reported oral bioavailabilities below 8.0% in cynomolgus monkeys and values as high as 92% in dogs. Reported oral bioavailabilities in rodents ranged from 12% to 57%. Using different presumptions, we estimated human oral bioavailability of GS-441524 at 13% and 20%. Importantly, doses of GS-441524 lower than the 13 mg/kg dose used in the first-in-human trial may be effective against Covid-19. Also, GS-441524 appears to be well-tolerated. In conclusion, GS-441524 has potential for oral treatment of Covid-19.