Other RdRp inhibitors: sofosbuvir, galidesivir

Some other RdRp inhibiting compounds have also been discussed. Sofosbuvir is a polymerase inhibitor which is also used as a direct-acting agent in hepatitis C. It is usually well tolerated. Modelling studies have shown that sofosbuvir could also inhibit RdRp by competing with physiological nucleotides for the RdRp active site (Elfiky 2020). Sofosbuvir could be combined with HCV PIs. The first randomized controlled trial in adult patients hospitalized with COVID-19 in Iran to evaluate the efficacy and safety of the two HCV drugs sofosbuvir and daclatasvir in combination with ribavirin (SDR) compared these drugs with standard of care (Abbaspour Kasgari 2020). Though there were trends in favor of the SDR arm for recovery and lower death rates, the trial was too small to make definite conclusions. In addition, there was an imbalance in the baseline characteristics between the arms.

Galidesivir is a nucleoside RNA polymerase inhibitor with broad-spectrum activity in vitro against more than 20 RNA viruses in nine different families, including coronaviruses and other viral families. A NIAID-funded, randomized, double-blind, placebo-controlled clinical trial to assess the safety, clinical impact and antiviral effects of galidesivir in patients with COVID-19 is underway. Of note, the drug also works against Zika: in the study presented here, galidesivir dosing in rhesus macaques was safe and offered post-exposure protection against Zika virus infection (Lim 2020).

Find the entire treatment chapter at https://covidreference.com/treatment



AcalabrutinibAnticomplement therapiesAzithromycinCamostatChloroquineColchicineConvalescent plasmaCorticosteroidsCytokine blockersFamotidineFavipiravirG-CSFHuman recombinant soluble ACE2HydroxychloroquineIbrutinibIloprostInterferonsJAK inhibitorsLeflunomideLopinavirMonoclonal antibodiesN-acetylcysteineOseltamivir(other) Protease inhibitors(other) RdRp inhibitorsREGN-COV2Umifenovir

Outlook | References

By Christian Hoffmann