Molnupiravir

Molnupiravir
Clinical data
Pronunciation/ˌmɔːlnuˈpɪərəvɪər/ MAWL-noo-PEER-ə-veer
Trade namesLagevrio
Other namesMK-4482, EIDD-2801
AHFS/Drugs.comMonograph
MedlinePlusa622027
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
  • N-Hydroxy-5'-O-isobutyryl-3,4-dihydrocytidine
    [(2R,3S,4R,5R)-3,4-Dihydroxy-5-[4-(hydroxyamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methyl 2-methylpropanoate (PIN)
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC13H19N3O7
Molar mass329.309 g·mol−1
3D model (JSmol)
  • CC(C)C(=O)OC[C@H]1O[C@@H](n2ccc(NO)nc2=O)[C@H](O)[C@@H]1O
  • InChI=1S/C13H19N3O7/c1-6(2)12(19)22-5-7-9(17)10(18)11(23-7)16-4-3-8(15-21)14-13(16)20/h3-4,6-7,9-11,17-18,21H,5H2,1-2H3,(H,14,15,20)/t7-,9-,10-,11-/m1/s1 checkY
  • Key:HTNPEHXGEKVIHG-QCNRFFRDSA-N checkY

Molnupiravir, sold under the brand name Lagevrio, is an antiviral medication that inhibits the replication of certain RNA viruses.[7] It is used to treat COVID‑19 in those infected by SARS-CoV-2.[7] It is taken by mouth.[7]

Molnupiravir is a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine and exerts its antiviral action by introducing copying errors during viral RNA replication.[13][14]

Molnupiravir was originally developed to treat influenza at Emory University by the university's drug innovation company, Drug Innovation Ventures at Emory (DRIVE), but was reportedly abandoned for mutagenicity concerns.[15][16] It was then acquired by the Miami-based company Ridgeback Biotherapeutics, which later partnered with Merck & Co. to develop the drug further.[17]

Based on positive results in placebo-controlled double-blind randomized clinical trials,[18][19] molnupiravir was approved for medical use in the United Kingdom in November 2021.[7][20][21][22] In December 2021, the US Food and Drug Administration (FDA) granted an emergency use authorization (EUA) to molnupiravir for use in certain populations where other treatments are not feasible.[10] The emergency use authorization was only narrowly approved (13–10) because of questions about efficacy and concerns that molnupiravir's mutagenic effects could create new variants that evade immunity and prolong the COVID‑19 pandemic.[23][24][25] In September 2023, molnupiravir's vial mutagenicity was confirmed to contribute to circulating SARS-CoV-2 genomic variation in a study of global SARS CoV 2 isolates after 2022: molnupiravir-specific genomic changes were more common, especially where molnupiravir had been used.[26]

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  2. ^ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Archived from the original on 3 April 2022. Retrieved 13 May 2022.
  3. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  4. ^ "TGA eBS - Product and Consumer Medicine Information Licence". Archived from the original on 5 February 2022. Retrieved 5 February 2022.
  5. ^ "AusPAR: Molnupiravir". Therapeutic Goods Administration (TGA). 8 February 2022. Archived from the original on 24 March 2022. Retrieved 23 March 2022.
  6. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control]. Diário Oficial da União (in Brazilian Portuguese) (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  7. ^ a b c d e "Summary of Product Characteristics for Lagevrio". Medicines and Healthcare products Regulatory Agency (MHRA). 4 November 2021. Archived from the original on 4 November 2021. Retrieved 4 November 2021.
  8. ^ "Regulatory approval of Lagevrio (molnupiravir)". Medicines and Healthcare products Regulatory Agency (MHRA). 4 November 2021. Archived from the original on 4 November 2021. Retrieved 4 November 2021.
  9. ^ "Molnupiravir capsule". DailyMed. Archived from the original on 14 January 2024. Retrieved 3 October 2023.
  10. ^ a b "Coronavirus (COVID-19) Update: FDA Authorizes Additional Oral Antiviral for Treatment of COVID-19 in Certain Adults". U.S. Food and Drug Administration (FDA) (Press release). 23 December 2021. Archived from the original on 23 December 2021. Retrieved 23 December 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  11. ^ O'Shaughnessy JA (22 March 2022). "Emergency Use Authorization 108". Letter to Merck Sharp & Dohme Corp. U.S. Food and Drug Administration (FDA).
  12. ^ Cite error: The named reference fda-factsheet was invoked but never defined (see the help page).
  13. ^ Toots M, Yoon JJ, Cox RM, Hart M, Sticher ZM, Makhsous N, et al. (October 2019). "Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia". Science Translational Medicine. 11 (515): eaax5866. doi:10.1126/scitranslmed.aax5866. PMC 6848974. PMID 31645453.
  14. ^ Toots M, Yoon JJ, Hart M, Natchus MG, Painter GR, Plemper RK (April 2020). "Quantitative efficacy paradigms of the influenza clinical drug candidate EIDD-2801 in the ferret model". Translational Research. 218: 16–28. doi:10.1016/j.trsl.2019.12.002. PMC 7568909. PMID 31945316.
  15. ^ Cohen B, Piller C (May 2020). "Emails offer look into whistleblower charges of cronyism behind potential COVID-19 drug". Science. doi:10.1126/science.abc7055.
  16. ^ Cully M (January 2022). "A tale of two antiviral targets - and the COVID-19 drugs that bind them". Nature Reviews. Drug Discovery. 21 (1): 3–5. doi:10.1038/d41573-021-00202-8. PMID 34857884. S2CID 244851870.
  17. ^ Aleccia J (29 September 2021). "Daily pill to treat COVID could be just months away". ABC News. Kaiser Health News. Archived from the original on 29 September 2021. Retrieved 29 September 2021.
  18. ^ Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos Reyes V, et al. (December 2021). "Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients". The New England Journal of Medicine. 386 (6): 509–520. doi:10.1056/NEJMoa2116044. PMC 8693688. PMID 34914868.
  19. ^ Singh AK, Singh A, Singh R, Misra A (November 2021). "Molnupiravir in COVID-19: A systematic review of literature". Diabetes & Metabolic Syndrome. 15 (6): 102329. doi:10.1016/j.dsx.2021.102329. PMC 8556684. PMID 34742052.
  20. ^ "First oral antiviral for COVID-19, Lagevrio (molnupiravir), approved by MHRA" (Press release). Medicines and Healthcare products Regulatory Agency (MHRA). 4 November 2021. Archived from the original on 5 January 2022. Retrieved 4 November 2021.
  21. ^ "Merck and Ridgeback's Molnupiravir, an Oral COVID-19 Antiviral Medicine, Receives First Authorization in the World". Merck & Co. (Press release). 4 November 2021. Archived from the original on 4 November 2021. Retrieved 4 November 2021.
  22. ^ Robbins R, Khan AJ, Specia M (4 November 2021). "Britain Becomes First to Authorize an Antiviral Pill for Covid-19". The New York Times. Archived from the original on 28 November 2021. Retrieved 27 November 2021.
  23. ^ Kimball S (30 November 2021). "FDA advisory panel narrowly endorses Merck's oral Covid treatment pill, despite reduced efficacy and safety questions". CNBC. Archived from the original on 1 January 2022. Retrieved 1 January 2022.
  24. ^ Lin MZ (24 December 2021). "A new drug to treat covid could create a breeding ground for mutant viruses". The Washington Post. Archived from the original on 30 December 2021. Retrieved 1 January 2022.
  25. ^ Service RF (November 2021). "A prominent virologist warns COVID-19 pill could unleash dangerous mutants. Others see little cause for alarm". Science. doi:10.1126/science.acx9591.
  26. ^ Cite error: The named reference nature23 was invoked but never defined (see the help page).