Favipiravir

High concentrations were required to reduce the viral infection

Favipiravir (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million U twice daily) showed significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance than lopinavir/ritonavir (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million U twice daily).

Favipiravir treatment did not improve clinical recovery rate of day 7 (61.21%) compared to arbidol group (51.67%). However, it did significantly improve the latency to cough relief and decreased the duration of fever.

The drug inhibited SARS-CoV-2 in Vero E6 cells with an EC50 of 204 μM. At 125 mM, ≥2-fold infectious titre reduction was observed (ca. 5-fold in Caco-2 cells). It displayed low toxicity in vitro. High dose favipiravir administration in a hamster model prior or concurrently with a viral challenge led to a significant reduction in infectious titres and lung damage, signs of toxicity were observed, however. Favipiravir induced mutations into the viral genome.

Significantly increases viral clearance in 4 days. in patients with moderate severity of COVID-19. Sample size: 20 (higher dose) + 20 (lower dose) + 20 control. Dosage: Twice daily 1800 mg on the 1st day, 800 mg on days 2-14 (higher dose group); twice daily 1600 mg on the 1st day, 600 mg on days 2-14 (lower dose group). Endpoint (in the trial design):  Elimination of SARS-CoV-2 by day 10 (2 negative PCR tests).

modest reduction in viral load; not effective as prophylaxis

Treatment resulted in recovery after clinical and chest imaging improvement. Sample size: 3. Dosage: 1800 mg twice daily on day 1, 800 mg twice daily on days 2–14.

Treatment in combination with short-course systemic prednisolone. Administration resulted in clinical improvement, PCR negativity and antibody seropositivity against SARS-CoV-2. Sample size: 1. Dosage: Twice IV 1800 mg on day 1 and 800 mg on days 2-9.

Early treatment (in combination with methylprednisolone) in severe COVID-19 may prevent disease progression. Sample size: 11. Dosage: 1.8 g twice daily on day 1; 0.8 g twice daily on days 2-14 (data available only for a single case). 

Clinical improvement and viral load supression below detectiol limit in a diabetic nephropathy patient non-responsive to lopinavir/ritonavir and ciclesonide therapy. Dosage: 3600 mg loading dose; 800 mg twice daily for 2 weeks.

Favipiravir is incorporated into the error-prone SARS-CoV-2 RNA-dependent RNA polymerase’s product and introduced mutations are lethal for the virus.

Rapid SARS-CoV-2 RNA elimination in majority of the patients after favipiravir treatment. Sample size: 8. Dosage: 1600 mg twice on day 1; 600 mg twice daily on days 2–10 or until SARS-CoV-2 RNA negative.

Predicted to bind the SARS-CoV-2 RNA-dependent RNA polymerase active site and the terminus of the replicated RNA.

Favipiravir significantly shortened the length of ICU stay (of the discharged patients) in critically ill COVID-19 patients compared to patients treated with lopinavir/ritonavir (LPV/r). The proportion of discharged patients at the selected time point was higher in the favipiravir group (not significantly). The death rate was (not significantly) increased in favipiravir group, however. Sample size: 65 + 42 LPV/r. Dosage: 1600 mg twice on day 1; 600 mg daily on days 2-5.

Predicted to bind the SARS-CoV-2 spike protein RBD.

Numerical improvement in primary endpoint (although without statistical significance, possibly due to technical limitations), statistically significant reduction of time to clinical cure in the treatment group compared to the control. Sample size: 70 + 68 control (completed). Dosage: 1800 mg twice daily on day 1; 800 mg twice daily on days 2-14. Endpoints: Time to cessation of viral shedding (primary).

Favipiravir treatment was associated with clinical and laboratory improvement in majority of patients. There was no control group, however. Sample size: 40. Dosage: 1600 mg twice on day 1; 600 mg twice a day for 5 to 7 days.

Numerically (but not statistically significant) shorter length of hospital stay and lower need for mechanical ventilation was observed in favipiravir-treated patients compared to the

The favipiravir triphosphate metabolite was shown to be incorporated into nascent replicated viral RNA chain. Unlike in some other nucleoside analogues, favipiravir nucleotides do not terminate polymerization but base-pair both with uracils and cytosines (favipiravir competes with purines during polymerisation). Thus, mutations are introduced into viral progeny.

Favilavir was computationally modelled to bind at the SARS-CoV-2 RNA-dependent RNA polymerase active site. In contrast to remdesivir, it was predicted not to base-pair significantly with the complementary RNA strand.

Favipiravir nucleosides bind mostly non-productively at the SARS-CoV-2 RNA-dependent RNA polymerase catalytic site and thus serve as a poor substrate for RNA primer extension in vitro. However, some of the favipiravir nucleosides are incorporated into the nascent RNA chain. These likely induce mutagenesis lethal for the virus.

The early treatment displayed efficacy in fever alleviation. Sample size: 41 (efficacy analysis) of which 30 in the early treatment group. Dosage: 1,800 mg twice on day 1; 800 mg twice a day for a maximum of 14 days.

The drug was generally safe and shortened the duration of SARS-CoV-2 viral shedding in patients with persistent viral RNA-positivity. Sample size: 36 + 19 control. Dosage: Two doses of 1,600 mg on day 1; 600 mg twice a day on days 2–7 (optionally up until day 14). Primary outcome: Time to two consecutive negative RT-PCR tests.

Among patients treated with favipiravir, shorter time to hospital discharge and slower progression to mechanical ventilation compared to the supportive care only group were observed. No significant difference in mortality was observed, however. Numerical trend toward worse clinical outcome was observed in critically ill patients, too. Sample size: 234 + 223 control. Dosage: 1800 mg or 1600 mg twice daily on day 1, then 800 mg or 600 mg twice daily. Primary outcome: Time to hospital discharge.

When combined with molnupiravir, a reduction in lung viral titres was observed in a hamster model. The combinational treatment also prevented infection transmission among co-housed animals.