**2.9 Favipiravir**

Favipiravir (FPV) is a purine nucleotide that inhibits viral RNA polymerase. It was initially used against Ebola but later found to have in-vitro activity against other RNA viruses. The EC50 (concentration of a drug that gives half-maximal response) of FPV against SARS-CoV-2 in vitro in Vero E6 cells was found to be 61.88 μM/L [6, 61]. A study investigated the effect of FPV vs. lopinavir/ritonavir on the treatment of COVID-19. FPV was independently associated with faster viral clearance and a higher improvement rate in chest imaging. These findings suggest that FPV has significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance as compared with lopinavir/ritonavir [62]. In an RCT on moderate to severe COVID patients, FPV was compared with umifenovir (Arbidol) by measuring the clinical recovery at 7 days [63]. Results showed no significant differences between the 2 groups. At present, there are no recommendations for the use of FPV in Covid-19 patients. Just like HCQ & lopinavir/ritonavir combination, it also causes QT prolongation [20].

#### **2.10 Ribavirin**

Ribavirin, a guanine analog, inhibits viral RNA dependent RNA polymerase (RdRp). It has demonstrable activity against many coronaviruses, but when used against SARS-CoV it was found to have less effectiveness in vitro requiring higher doses with combination therapy. When used with interferon in the treatment of MERS-CoV, no benefits were observed in terms of clinical outcomes or the rate of virus clearance [64]. Ribavirin also causes dose-dependent hematological toxicity & transaminase elevation when used in SARS patients and being a teratogen, is contraindicated in pregnancy [65, 66]. A recent trial showed ribavirin not being associated with better negative conversion times for the SARS-CoV-2 test and not being associated with improved mortality rates [67]. Due to its lack of demonstrable efficacy against other coronaviruses and high toxicity profile, it has got a limited

role in the treatment of Covid-19. However, its combination with other antivirals is being tried in the SEV trial, the result of which is yet to be published [68].
