Molnupiravir
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Molnupiravir is a new potential drug against the SARS-CoV-2 infectious virus.
To this date, all medications against SARS-CoV-2 are administered only by infusion and only in severe disease cases (e.g., Remdesivir - Gilead and monoclonal antibody - Regeneron). Therefore, the aim is to find a drug administered orally to prevent the severe stage of Covid-19. These conditions could be met by Molnupiravir, which has successfully completed Phase 3 of clinical trials. According to the initial results, Molnupiravir highly reduces hospitalization and also mortality. Therefore, the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) have become interested in Molnupiravir, from which the manufacturer is requesting accelerated approval, as in the case of Remdesivir (Gilead).
Molnupiravir was initially developed by a non-profit company DRIVE (Drug Innovation Ventures at Emory) as a drug for the Venezuelan equine encephalitis virus in Atlanta but was also tested for various coronavirus strains with positive results. DRIVE has licensed Ridgeback Biotherapeutics and Merck to make the medicine available as soon as possible.
One interesting fact, the name of Molnupiravir was inspired by Thor's hammer, Mjölnir.
Molnupiravir is used as a prodrug. It breaks down into a free ribonucleoside derivative inside the cell, and kinases convert the nucleoside into its relative 5‘-O-triphosphate, responsible for antiviral activity. The 5'-O-triphosphate (β-D-N4-4-Hydroxycytidine 5′-triphosphate, EIDD-1931 5′-triphosphate or NHC-TP) is incorporated into the nascent viral RNA by RNA polymerase, causing mutations and the consequent extinction of the virus. This effect is generally called lethal mutagenesis. Molnupiravir can change its structure by tautomerism between a uridine-like form and a cytidine-like form, and thus disguise itself from the virus providing an advantage over other antiviral agents to which some viruses can develop resistance over time.
This tautomerism stands at the basis of Molnupiravir’s antiviral activity: the viral RNA dependent RNA polymerase can incorporate either adenosine or guanosine complementary to the quickly changing forms of Molnupiravir, introducing thus mutations into the RNA.
Due to its mechanism of action, this active substance should have a higher potential for broad-spectrum applications.
Approval of Molnupiravir would improve the availability of drugs for Covid-19 for everyone. In November 2021, Molnupiravir was approved for medical use in the United Kingdom.
Antiviral laboratories are also testing Molnupiravir triphosphate in vitro studies for a deeper understanding of the mechanism of action.
If you would like to know more about Molnupiravir or Molnupiravir triphosphate, or if we can help you with your research, write an email to Krystof Sigut on krystof.sigut@santiago-lab.com or reach him on the phone +420 776 750 591.
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References:
https://www.nature.com/articles/d41586-021-02783-1
https://www.ema.europa.eu/en/news/covid-19-ema-starts-rolling-review-molnupiravir
https://www.medrxiv.org/content/10.1101/2021.06.17.21258639v1.full.pdf
https://en.wikipedia.org/wiki/Molnupiravir
https://www.science.org/content/blog-post/molnupiravir-mutations
https://clinicaltrials.gov/ct2/show/NCT04575597
https://www.bbc.com/news/health-59163899
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