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Molnupiravir is a preparation of Molnupiravir. It is an antiviral drug which is orally active and is developed for the treatment of influenza. It is a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine, and exerts its antiviral action through introduction of copying errors during viral RI\IA replication including SARS-CoV-2, the causative agent of C0VID-19. Molnupiravir is a shape-shifter, called a tautomer. It assumes two forms, one which closely resembles uracil and the other cytosine. Because it appears in these two different forms, once it is recopied, the replicating polymerase develops transition mutations, where a U nucleotide is converted to a C and a C to U. Copying RNA that contains Molnupiravir results in fatal flaws in the sequence, stopping replication, shortening infection, and limiting transmission. The difference between the structure of an authentic nucleotide and Molnupiravir is apparently too subtle to trigger removal by the exonuclease repair function of the viral polymerase, a function that has bedeviled these of many other nucleoside inhibitors.
Pharmacology
Molnupiravir inhibits viral reproduction by promoting widespread mutations in the replication of viral RNA by RNA-directed RNA polymerase. It is metabolized into a ribonucleoside analog that resembles cytidine, β-D-N 4-Hydroxycytidine 5′-triphosphate (also called EIDD-1931 5′-triphosphate or NHC-TP). During replication, the virus's enzyme incorporates NHC-TP into newly-made RNA instead of using real cytidine.
Molnupiravir can swap between two forms (tautomers), one of which mimics cytidine (C) and the other of which mimics uridine (U). NHC-TP is not recognized as an error by the virus' proofreading exonuclease enzymes, which can replace mutated nucleotides with corrected versions. When the viral RNA polymerase attempts to copy RNA containing molnupiravir, it sometimes interprets it as C and sometimes as U. This causes more mutations in all downstream copies than the virus can survive, an effect called viral error catastrophe or lethal mutagenesis.
Molnupiravir is an antiviral medicine used to treat mild to moderate C0VID-19 (caused by SARS-CoV-2) in adults who are at risk for developing severe illness. Molnupiravir may help people with C0VID-19 stay out of the hospital and feel better. Emergency use authorized oral therapeutic for the treatment of C0VID-19 in Non-hospitalized patients with mild or moderate disease.
Asymptomatic or pre-symptomatic Infection: Individuals who test positive for SARS-CoV-2 by virologic testing using a molecular diagnostic (e.g., polymerase chain reaction) or antigen test, but have no symptoms.
Mild illness: individuals who have any of the various signs and symptoms of COVID-19 (e.g., fever, cough, sore throat, malaise, headache, muscle pain) without shortness of breath, dyspnoea, or abnormal chest imaging.
Moderate illness: Individuals who have evidence of lower respiratory disease by clinical assessment or imaging and saturation of oxygen (Sp02) >94% on room air at sea level.
Severe illness: Individuals who have respiratory frequency >30 breaths per minute, Sp02 <94% on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (Pa02/Fi02) <300 mmHg, or lung infiltrates >50%.
Critical illness: individuals who have respiratory failure, septic shock, and/or multiple organ dysfunction.
The recommended dose of Molnupiravir is four 200 mg capsules (4+0+4), every 12 hours for 5 days. Do not give this medicine to children and adolescents aged less than 18 years. The use of Molnupiravir in persons aged less than 18 years has not yet been studied.
Molnupiravir is contraindicated in patients with known hypersensitivity to Molnupiravir.
Common side effects include diarrhoea, nausea, feeling dizzy, headache.
There are limited clinical data available for Molnupiravir. Serious and unexpected adverse events may occur that have not been previously reported with Molnupiravir use.
Pregnancy & Lactation
Animal studies with molnupiravir have shown harmful effects to the unborn animal. Molnupiravir is not recommended in pregnancy. Molnupiravir has not been studied in pregnancy and it is not known if Molnupiravir will harm your baby while you are pregnant. If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for advice. If you can become pregnant, you should use effective birth control while you are taking Molnupiravir and for 4 days after the last dose of Molnupiravir. If you are breast-feeding or are planning to breastfeed, tell your doctor before taking this medicine. Breast-feeding is not recommended during treatment and for 4 days after the last dose of Molnupiravir. This is because it is not known if Molnupiravir gets into breast milk and will be passed to the baby.