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.