What Is Molnupiravir?
The USFDA issued the orders to EUA (emergency use authorization) in December 2021 for using the antiviral pill Molnupiravir in the treatment of mild to moderate COVID-19 infections. The order also indicated its use in treating COVID-affected patients, particularly those at high risk for progression to severe infection that is mainly individuals predisposed to the risk of hospitalization and mortality. Molnupiravir is currently one of the three approved drugs for restricted emergency use in India to combat the omicron variant's peaking mutations. Serum Institute of India's Covovax and Biological E. Limited's Corbevax vaccines are the other two granted permission presently for use in certain conditions, taking into account the patient's risk assessment status for developing severe COVID infection.
What Is the Dosage of Molnupiravir?
In collaboration with Ridgeback and Merck, this drug is being developed in bulk to be administered as 200 mg capsules that are to be taken orally for five days every 12 hours. The maximum recommended dosage in mild to moderately affected patients (with hospitalization risks) should not be more than 40 capsules. Also, the number of days should not exceed five days. Molnupiravir is strictly not authorized presently for use longer than five consecutive days.
How Is Molnupiravir Manufactured?
In India, Merck & Co has now signed a voluntary licensing agreement with the well-known Cipla and Dr. Reddy's laboratories, Emcure Pharmaceuticals, Hetrolabs Private Limited, and Sun pharmaceuticals Limited for marketing. This drug's usage is restricted to adult COVID patients only in certain conditions, mainly with an Sp02 of 93% with progressive signs and symptoms that have not subsided.
According to the USFDA, Molnupiravir is not recommended in pregnant women for pre-exposure or post-exposure prophylactic concerns to prevent coronavirus infections because it has the potential to be teratogenic or cause congenital disabilities. Molnupiravir is also not authorized for use in children for safety concerns because it has the potential to interfere with bone growth. This easy sue COVID pill can be taken within five days from the comfort of home as per a healthcare practitioner's or physician's consent and prescription as soon as the symptoms start. These include cough, headache, fever, loss of taste or smell, body aches, fatigue, and also muscle aches in a few individuals.
What Is the Mechanism of Action of Molnupiravir?
Molnupiravir is an isopropyl ester prodrug of the nucleoside analog β-D-N4-hydroxycytidine. The structure of Molnupiravir, as per scientific research and subsequent clinical trials in human and animal models, has also enabled mechanistic studies that can rationalize the molecular processes underlying the antiviral activity of compounds targeting RdRp (RNA dependent RNA polymerase).
Coronaviruses use this RNA-dependent RNA polymerase (RdRp) for the replication and transcription of the RNA genome. RdRp is an essential target for developing antiviral drugs against the coronavirus family and its numerous variants and emerging mutations in its genome. Documented evidence shows that the drug mainly targets RdRp, inhibits SARS-CoV-2 replication in human lung tissue blocks, and simultaneously reduces SARS-CoV-2 RNA in patients.
As the current omicron variant of the novel coronavirus has multiple mutations bound to its S/spike protein part, Molnupiravir is so far deemed to be efficacious against the omicron variant because it does not target the spike protein but the RdRp rather.
In contrast to approved drugs like Remdesivir administered only by infusion, Molnupiravir is in the pill form, which can be taken easily as it is orally administered, in mild to moderate COVID cases, especially those under home isolation and quarantine. Molnupiravir was tested before being recommended for emergency usage in phase I and II trials regarding its efficacy, safety, tolerability, and pharmacokinetics.
Though a detailed systematic biochemical and structural analysis of Molnupiravir induced mutagenesis by viral RNA polymerases is lacking, research models and the recent nod to its emergency usage in mild to moderate COVID infections make this antiviral drug a suitable choice in emergency prevention of mortality and hospitalization risks. Hence its use should strictly be decided, as per the extent of COVID infection determined by the physician.
Molnupiravir mainly increases the frequency of viral RNA mutations and thus impairs SARS-CoV-2 replication, as observed in clinical trials in animal and human models. Phase III trials have thoroughly understood the molecular mechanisms underlying Molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp).
What Are the COVID Vaccines Now in Use?
Newly introduced emergency vaccines that have the vaccine market, as permitted by the central drug standard control organization-CDSCO) are:
- Corbevax vaccine is India's first RBD protein subunit vaccine (Hyderabad-based firm Biological-E) against COVID-19 infection.
- Covovax is the Serum institute of Pune's nanoparticle vaccine developed for emergency isolation use.
These two vaccines were indigenously introduced into the vaccine market along with the already pre-existing authorized and full-fledged COVID-19 vaccines for public use, i.e., Covaxin, ZyCoV-D, Sputnik V, Moderna, Johnson and Johnson, and now the emergency oral antiviral COVID pill. Molnupiravir can boost public immunity both by a standard regimen of vaccine administration and for patients who need an immunity boost against the new variants like delta and omicron.
In Whom Is Molnupiravir Not Recommended?
Due to mutagenicity concerns, fetal teratogenicity, and bone or cartilage toxicity, Molnupiravir is not for children, pregnant women, young adults below 18 years of age, or the lactating population. Hence, considering the current clinical outcomes and efficacy of this drug, the dosage and clinical status still need monitoring by the physician for upto a maximum of five days based on the patient's predisposition, risk, and systemic condition.
Conclusion:
To conclude, Molnupiravir drug is a potent viral RNA inhibitor and thus safe for restricted use as an oral antiviral drug in the treatment of COVID infection, which, indeed, is a novel effort to counteract and limit mortality in an exceeding population affected by the newer variants of the SARS COV-2 Pathogen.
