Virology and Safety profile of Molnupiravir at three different doses: A
systematic review and Meta-analysis
Abstract
Molnupiravir (also known as EIDD-2801/MK-4482), which is used as an
antiviral drug has its mechanism of action by incorporating into the
viral genome increasing errors, mismatching, and misdirecting the viral
polymerase, leading to the accumulation of deleterious errors and
halting viral RNA replication of SARS-CoV-2 and other RNA viruses. Our
meta-analysis aims to evaluate virology profile, and adverse effects
associated with the use of molnupiravir on a large patient population.
Following PRISMA guidelines performed a thorough literature search of
electronic and medical databases (MEDLINE and Cochrane CENTRAL) from
their establishment to January 2023 without any limitations on time,
language, or sample size. The random effects model was utilized to
calculate the weighted mean difference (WMD) and its associated 95%
confidence intervals (CIs) to pool continuous outcomes of interest.
Using a random effects model, odds ratio, and accompanying 95%
confidence intervals (CIs). Molnupiravir 800 mg at day 5 is significant
in creating viral RNA error rate (WMD: 4.91; 95% CI; [1.19, 8.63]
p=0.01; I 2=0%). (P-value for subgroup differences =
0.05). A significant outcome was reported with 400mg molnupiravir (WMD:
2.27; 95% CI; 2.27 [0.50, 4.65] p=0.02; I 2=0%).
Significant outcome for mean change in SARS-COV-2 RNA viral load from
baseline in nasopharyngeal sample at 800 mg molnupiravir on day 3 (WMD:
-0.22; 95% CI; [-0.35,-0.08] p=0.002; I 2=0%),
day 5 (WMD: -0.32; 95% CI; [-0.53,-0.11] p=0.003; I
2=24%) and overall pooled analysis (WMD: -0.17; 95%
CI; [-0.29, 0.33] p=0.003; I 2=32%). Similarly
for 400 mg at DAY 5 and overall analysis comparing the molnupiravir
group to the placebo group, a significant reduction in viral RNA load
was seen from baseline. (WMD: -0.46; 95% CI; [-0.77,-0.15] p=0.004;
I 2=0%), (WMD: -0.28; 95% CI; [-0.49,-0.07]
p=0.009; I 2=0%). Molnupiravir 400mg significantly
reduced the incidence of death as compared to the placebo group. (RR:
0.17; 95% CI; [0.07, 0.43] p=0.0002; I 2=0%). In
our meta-analysis, we conclude that molnupiravir is effective in
treating SARS-COV-2 patients with respect to eliminating the virus from
the host through their mechanism of action. Thereby, widely used and
appropriate to treat SARS-COV-2.