2 In Use

Remdesivir (GS-5734) , a nucleotide analogue, is one of the most promising drugs available against COVID-19. It is the only drug so far that has been approved by the FDA outside the context of a clinical trial albeit in emergency situations only. It has a broad spectrum anti-viral activity and has been used against Ebola as well as the SARS and MERS Corona viruses in the past 23. It has shown in vitro and in vivo activity against SARS-COV-2 4. It is a small molecule inhibitor of viral RNA polymerase. It can also interfere with the Corona Virus nsp12 polymerase activity and can generate active nucleotide triphosphates which incorporate into RNA strands followed by termination of viral RNA replication5.
Several clinical trials are currently underway to further investigate its role as a therapeutic option in COVID-19. Among them was a recent randomized, double-blind, placebo controlled, multi-center trial of 1063 globally dispersed patients. In the treatment group, hospitalized COVID-19 patients were administered an initial intravenous loading dose of 200 mg Remdesivir followed by daily intravenous maintenance dose of 100 mg for 5–9 days. The recovery time in this group was significantly shorter than that observed in the placebo group (median, 11 days vs 15 days). The incidence of adverse events (anemia, acute kidney injury, decreased creatinine clearance, pyrexia, hyperglycemia and increased aminotransferase levels) was not found to be significantly different between the two groups 6.
Lopinavir/ Ritonavir belong to antiretroviral drugs and belong to protease inhibitors class. Ritonavir increases half-life of Lopinavir by inhibiting CYP450. Fixed dose combination (kaletra) has been used for the treatment of AIDS. The combination has been proposed to inhibit the SARS-CoV-2 protease chymotrypsin-like protease (3CLpro) that is necessary for the processing of the viral RNA although there is still some uncertainty as 3CLpro lacks the specific molecular site which is the target for these inhibitors 7.
Lopinavir-Ritonavir have been found effective against COVID-19 when used in combination with other antivirals but not so much on their own. A multi-centered open labeled randomized study was carried out in six major hospitals of Hong Kong. Confirmed COVID-19 positive patients (n=86) above the age of eighteen were randomized to the treatment group who received the triple combination of Lopinavir- Ritonavir (400mg-100mg) every 12 hours, Ribavirin (400mg) every 12 hours, and subcutaneous injection of Interferon Beta-1b, three doses of eight million units on alternate days. They had a shorter median time to testing negative when compared with the control group patients (n=41) treated with Lopinavir-Ritonavir only. All symptoms of the patients of the triple combination group resolved in 4 days vs 8 days in the Lopinavir-Ritonavir group. Standard care was provided to both groups. Common non-serious adverse events such as diarrhoea, nausea, fever and the raised liver enzyme ALT were observed 8.
Recently, the FDA recommended against the use of Lopinavir/Ritonavir unless patients are involved in a clinical trial.
Avifavir (favipiravir) is related to Avigan, an anti-influenzal drug that is used in Japan. It is also a small molecule inhibitor of viral RNA polymerase. The median viral clearance time of patients with COVID-19 who received oral Favipiravir (35 patients) was shorter than patients who received Lopinavir/Ritonavir (45 patients), 4 vs 11days. Both treatment groups were additionally treated with interferon administered by aerosol inhalation. The incidence of adverse effects was also less in the first group. They also showed more significant improvements when comparing chest imaging 9. Russia has granted temporary approval for Avifavir and they will deliver approximately 60,000 courses of Avifavir to Russian hospitals in June.
Arbidol (Umifenovir) is a broad-spectrum antiviral compound. A trial was conducted at a hospital in Changzhou to compare the efficacy of Arbidol to Lopinavir/Ritonavir. Thirty-four COVID-19 patients received Lopinavir/Ritonavir at a dose of 400mg/100mg twice a day for a week while 16 patients received 200mg of Arbidol thrice a day. While there was no significant difference between the duration of fever in both groups the patients of the Arbidol group reached undetectable levels of the RNA by day 14 after admission while this was not the case for 44.1% of the patients in the group receiving Lopanivir/Ritonavir10, suggesting that Arbidol may be a better alternative to Lopinavir/ Ritonavir. However, the small sample size was the major limitation in this study. Favipiravir was found to have better outcomes than Arbidol, although there was no difference in the mechanical ventilation rates in both groups, the fever of the Favipiravir patient group decreased earlier 11.