Molnupiravir

Last updated

Molnupiravir
MK-4482.svg
Clinical data
Trade names Lagevrio
Other namesMK-4482, EIDD-2801
AHFS/Drugs.com Monograph
License data
Pregnancy
category
Routes of
administration
By mouth
ATC code
  • None
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
Chemical and physical data
Formula C13H19N3O7
Molar mass 329.309 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 Yes check.svgY
  • Key:HTNPEHXGEKVIHG-QCNRFFRDSA-N Yes check.svgY

Molnupiravir is an antiviral medication that inhibits the replication of certain RNA viruses. [5] It is used to treat COVID-19 in those infected by SARS-CoV-2. [5]

Contents

Molnupiravir is a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine and exerts its antiviral action through introduction of copying errors during viral RNA replication. [11] [12]

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. [13] [14] It was then acquired by Miami-based company Ridgeback Biotherapeutics, which later partnered with Merck & Co. to develop the drug further. [15]

Based on positive results in placebo-controlled double-blind randomized clinical trials, [16] [17] Molnupiravir was approved for medical use in the United Kingdom in November 2021. [5] [18] [19] [20] In December 2021, the U.S. Food and Drug Administration (FDA) granted an emergency use authorization (EUA) to molnupiravir for use in certain populations where other treatments are not feasible. [8] The emergency use authorization was only narrowly approved (13-10) because of questions regarding efficacy and concerns that molnupiravir's mutagenic effects could create new variants that evade immunity and prolong the COVID-19 pandemic. [21] [22] [23]

Medical uses

Molnupiravir is indicated for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19. [5] [8]

Contraindications

Use in pregnancy is not recommended. [3] There are no human data on use during pregnancy to assess the risk of adverse maternal or fetal outcomes. [3] Based on animal data, the drug may cause fetal harm. [3]

In rats, bone and cartilage toxicity was observed after repeated dosing. [10]

Adverse effects

Adverse reactions observed in the phase III MOVe-OUT study included diarrhea (2%), nausea (1%) and dizziness (1%), all of which were mild or moderate. [10]

Overdose

The effects of overdose are unknown, treatment consists of general supportive measures such as monitoring of clinical status. [10]

Drug interactions

There are no known drug interactions, although based on limited data available. [10]

Mechanism of action

Molnupiravir inhibits viral reproduction by promoting widespread mutations in the replication of viral RNA by RNA-directed RNA polymerase. [24] It is metabolized into a ribonucleoside analog that resembles cytidine, β-D-N4-Hydroxycytidine 5′-triphosphate (also called EIDD-1931 5′-triphosphate or NHC-TP). [25] [26] [27] During replication, the virus's enzyme incorporates NHC-TP into newly made RNA instead of using real cytidine. [27]

Molnupiravir metabolism.svg

Molnupiravir can swap between two forms (tautomers), one of which mimics cytidine (C) and the other of which mimics uridine (U). [28] NHC-TP is not recognized as an error by the virus' proofreading exonuclease enzymes, which can replace mutated nucleotides with corrected versions. [24] 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. [28]

Molnupiravir GC bonding.svg
Molnupiravir AU bonding.svg
Top, a G.molnupiravir base pair with three hydrogen bonds. Bottom, an A.molnupiravir base pair with two hydrogen bonds. Molnupiravir can mimic both C and U. [28] The wiggly lines stand for the connection to the pentose sugar and point in the direction of the minor groove.

Chemistry

The first synthesis of molnupiravir was disclosed in a patent filed by Emory University in 2018. [29]

In the first step, acetone is used as a protecting group to render two of the three hydroxy groups of uridine unreactive to treatment with the acid anhydride of isobutyric acid, which converts the third hydroxy group to its ester. Treatment with 1,2,4-triazole and phosphoryl chloride produces a reactive intermediate in which the triazole portion can be replaced with hydroxylamine. Finally, removal of the protecting group using formic acid converts the material to molnupiravir. [29] :93–95

Molnupiravir synthesis.svg

Alternative patented routes to molnupiravir have been reviewed. [30]

History

Molnupiravir was developed at Emory University by the university's drug innovation company, Drug Innovation Ventures at Emory (DRIVE). [15] In 2014, DRIVE began a screening project funded by the Defense Threat Reduction Agency to find an antiviral drug targeting Venezuelan equine encephalitis virus (VEEV), which led to the discovery of EIDD-1931. [31] [ unreliable medical source? ] When turned into the prodrug EIDD-2801 (molnupiravir), the compound also showed activity against other RNA viruses including influenza, Ebola, chikungunya, and various coronaviruses. [31]

The international nonproprietary name of the drug was inspired by that of Thor's hammer, Mjölnir. The idea is that the drug will strike down the virus, like a mighty blow from the god of thunder. [27]

In 2019, the National Institute of Allergy and Infectious Diseases (NIAID) approved moving molnupiravir into Phase I clinical trials for influenza. [31]

In March 2020, the research team pivoted to studying SARS-CoV-2, and successfully used the drug to treat human cells infected with the novel coronavirus. [31] [ unreliable medical source? ] A study found that molnupiravir is orally active against SARS-CoV-2 in ferrets. [32]

DRIVE then licensed molnupiravir for human clinical studies to Miami-based company Ridgeback Biotherapeutics, who later partnered with Merck & Co. to develop the drug further. [31] [15]

The primary data supporting the U.S. Food and Drug Administration (FDA) emergency use authorization for molnupiravir are from MOVe-OUT, a randomized, double-blind, placebo-controlled clinical trial studying molnupiravir for the treatment of non-hospitalized participants with mild to moderate COVID-19 at high risk for progression to severe COVID-19 and/or hospitalization. [8] [33] Participants were adults 18 years of age and older with a pre-specified chronic medical condition or at increased risk of SARS-CoV-2 infection for other reasons who had not received a COVID-19 vaccine. [8] The main outcome measured in the trial was the percentage of people who were hospitalized or died due to any cause during 29 days of follow-up. [8] Of the 709 people who received molnupiravir, 6.8% were hospitalized or died within this time period compared to 9.7% of the 699 people who received a placebo. [8] Of the people who received molnupiravir one died during the follow-up period compared to nine people who received placebo. [8]

Society and culture

Economics

In September 2021, Merck signed a voluntary licensing agreement with the Medicines Patent Pool (MPP) that allows MPP to sublicense molnupiravir and supply the COVID-19 oral medication to 105 low- and middle-income countries. The cost of the initial purchase made by the US government was about $712 per course of treatment, while treatment with generics in developing countries can cost as little as $20. [34] [35]

Merck submitted an EUA application to the FDA on 11 October 2021, and the FDA's Antimicrobial Drugs Advisory Committee (AMDAC) at the Center for Drug Evaluation and Research met to discuss the EUA application on 30 November 2021. [36] [37] The committee narrowly voted, (13 for and 10 opposed), to recommend authorization for adults with mild to moderate illness who are at high risk of developing severe COVID-19. [38] Concerns were expressed over the low effectiveness of the drug in preventing death, which in the final trial was only 30%, as well as the increased mutation rate caused by the drug, which could theoretically worsen the global pandemic by driving the evolution of more dangerous variants. [38] [14] In December 2021, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for molnupiravir for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate. [8]

In October 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) started a rolling review of molnupiravir. [39]

On 4 November 2021, molnupiravir was approved in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA) for the treatment of established infections of COVID-19. [5] The MHRA issued a conditional marketing authorization applicable in the United Kingdom, and an emergency use authorization for Northern Ireland. [5] [18] [40] [41]

In November 2021, the Bangladesh Directorate General of Drug Administration (DGDA) authorized emergency use of molnupiravir. [42] [43]

Names

Molnupiravir is the international nonproprietary name (INN). [44] [45]

Generic versions are available under the brand names Molulife (Mankind) and Molena (Emcure).[ citation needed ]

Public health concerns

Multiple advisors at the AMDAC meeting on 30 November 2021, raised the concern that molnupiravir could accelerate the emergence of variants of concern. [46] [47] Similar concerns were raised by other scientists both before and after the meeting. [48] [23] [49] [22]

Research

COVID-19 clinical trial

In October 2021, preliminary results from a clinical trial (MOVe-OUT) [50] [51] [ full citation needed ] indicate that treatment with molnupiravir may reduce the risk of hospitalization and death from COVID-19. [52] [53] The final analysis reported a 30% reduction in hospitalizations and deaths. [16] [54]

The efficacy against hospitalization or death in unvaccinated adults with mild or moderate COVID-19 and at least one risk factor for disease progression is about 30% (95% CI, 151%). [10]

As of 2022, the Panoramic trial is testing the effectiveness of molnupiravir. [55] [56]

Related Research Articles

Ritonavir Antiretroviral medication

Ritonavir, a protease inhibitor sold under the brand name Norvir, is an antiretroviral medication used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Often a low dose is used with other protease inhibitors. It may also be used in combination with other medications for hepatitis C. It is taken by mouth. The tablets of ritonavir are not bioequivalent to capsules as tablets may result in higher peak plasma concentrations.

Peramivir Antiviral drug targeting influenza

Peramivir is an antiviral drug developed by BioCryst Pharmaceuticals for the treatment of influenza. Peramivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and thereby preventing new viruses from emerging from infected cells. It is approved for intravenous administration.

An Emergency Use Authorization (EUA) in the United States is an authorization granted to the Food and Drug Administration (FDA) under sections of the Federal Food, Drug, and Cosmetic Act as added to and amended by various Acts of Congress, including by the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA), as codified by 21 U.S.C. § 360bbb-3, to allow the use of a drug prior to approval. It does not constitute approval of the drug in the full statutory meaning of the term, but instead authorizes the FDA to facilitate availability of an unapproved product, or an unapproved use of an approved product, during a declared state of emergency from one of several agencies or of a "material threat" by the Secretary of Homeland Security.

Baricitinib Chemical compound

Baricitinib, sold under the brand name Olumiant among others, is a medication used for the treatment of rheumatoid arthritis and COVID-19. It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2.

Remdesivir Antiviral drug

Remdesivir, sold under the brand name Veklury, is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is administered via injection into a vein. During the COVID‑19 pandemic, remdesivir was approved or authorized for emergency use to treat COVID‑19 in numerous countries.

Moderna COVID-19 vaccine RNA COVID-19 vaccine

The Moderna COVID‑19 vaccine, sold under the brand name Spikevax, is a COVID-19 vaccine developed by American company Moderna, the United States National Institute of Allergy and Infectious Diseases (NIAID), and the Biomedical Advanced Research and Development Authority (BARDA). It is authorized for use in people aged twelve years and older in some jurisdictions and for people eighteen years and older in other jurisdictions to provide protection against COVID-19 which is caused by infection by the SARS-CoV-2 virus. It is designed to be administered as two or three 0.5 mL doses given by intramuscular injection at an interval of at least 28 days apart.

COVID-19 drug repurposing research Drug repurposing research related to COVID-19

Drug repositioning is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed. This is one line of scientific research which is being pursued to develop safe and effective COVID‑19 treatments. Other research directions include the development of a COVID‑19 vaccine and convalescent plasma transfusion.

COVID-19 drug development Preventative and therapeutic medications for COVID-19 infection

COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research, with 419 potential COVID-19 drugs in clinical trials, as of April 2021.

GS-441524

GS-441524 is a nucleoside analogue antiviral drug which was developed by Gilead Sciences. It is the main plasma metabolite of the antiviral prodrug remdesivir, and has a half-life of around 24 hours in human patients. Remdesivir and GS-441524 were both found to be effective in vitro against feline coronavirus strains responsible for feline infectious peritonitis (FIP), a lethal systemic disease affecting domestic cats. Remdesivir was never tested in cats, but GS-441524 has been found to be effective treatment for FIP and is widely used despite no official FDA approval due to Gilead's refusal to license this drug for veterinary use.

There are no specific, effective treatments or cures for coronavirus disease 2019 (COVID‑19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus., but as of April 2022, several medications have been approved in different countries. Patients with mild to moderate symptoms who are in the risk groups can take nirmatrelvir/ritonavir or remdesivir, either of which reduces the risk of serious illness or hospitalization. In the US, the Biden Administration COVID-19 action plan includes the Test to Treat initiative, where people can go to a pharmacy, take a COVID test, and immediately receive free Paxlovid if they test positive.

Casirivimab/imdevimab Antiviral combination medication

Casirivimab/imdevimab, sold under the brand name REGEN-COV among others, is a combination medicine used for the treatment and prevention of COVID-19. It consists of two human monoclonal antibodies, casirivimab and imdevimab that must be mixed together and administered as an infusion or subcutaneous injection. The combination of two antibodies is intended to prevent mutational escape. It is also available as a co-formulated product. It was developed by the American biotechnology company Regeneron Pharmaceuticals.

Bamlanivimab is a monoclonal antibody developed by AbCellera Biologics and Eli Lilly as a treatment for COVID-19. The medication was granted an emergency use authorization (EUA) by the US Food and Drug Administration (FDA) in November 2020, and the EUA was revoked in April 2021.

Janssen COVID-19 vaccine Vaccine against COVID-19

The Janssen COVID-19 vaccine, or Johnson & Johnson COVID-19 vaccine, sold under the brand name Jcovden, is a COVID-19 vaccine that was developed by Janssen Vaccines in Leiden, Netherlands, and its Belgian parent company Janssen Pharmaceuticals, a subsidiary of American company Johnson & Johnson.

Bamlanivimab/etesevimab is a combination of two monoclonal antibodies, bamlanivimab and etesevimab, administered together via intravenous infusion as a treatment for COVID-19. Both types of antibody target the surface spike protein of SARS‑CoV‑2.

Chloroquine and hydroxychloroquine during the COVID-19 pandemic

Chloroquine and hydroxychloroquine are anti-malarial medications also used against some auto-immune diseases. Chloroquine, along with hydroxychloroquine, was an early experimental treatment for COVID-19. Neither drug prevents SARS-CoV-2 infection.

Nirmatrelvir COVID-19 antiviral medication

Nirmatrelvir is an antiviral medication developed by Pfizer which acts as an orally active 3C-like protease inhibitor. It is part of the nirmatrelvir/ritonavir combination used to treat COVID-19. The combination is sold under the brand name Paxlovid.

Sotrovimab, sold under the brand name Xevudy, is a human neutralizing monoclonal antibody with activity against severe acute respiratory syndrome coronavirus 2, known as SARS-CoV-2. It is under development by GlaxoSmithKline and Vir Biotechnology, Inc. Sotrovimab is designed to attach to the spike protein of SARS-CoV-2.

Ridgeback Biotherapeutics is a Miami based biotechnology company, primarily known for their involvement in developing a successful COVID-19 medication.

Nirmatrelvir/ritonavir Antiviral combination medication

Nirmatrelvir/ritonavir, sold under the brand name Paxlovid, is a co-packaged oral medication used as a treatment for COVID-19. It contains the antiviral medications nirmatrelvir and ritonavir.

Bebtelovimab is a monoclonal antibody developed by AbCellera and Eli Lilly as a treatment for COVID-19.

References

  1. 1 2 3 "Lagevrio APMDS". Therapeutic Goods Administration (TGA). 21 January 2022. Retrieved 5 February 2022.
  2. "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Retrieved 13 May 2022.
  3. 1 2 3 4 "TGA eBS - Product and Consumer Medicine Information Licence".
  4. "AusPAR: Molnupiravir". Therapeutic Goods Administration (TGA). 8 February 2022. Retrieved 23 March 2022.
  5. 1 2 3 4 5 6 7 "Summary of Product Characteristics for Lagevrio". Medicines and Healthcare products Regulatory Agency (MHRA). 4 November 2021. Retrieved 4 November 2021.
  6. "Regulatory approval of Lagevrio (molnupiravir)". Medicines and Healthcare products Regulatory Agency (MHRA). 4 November 2021. Retrieved 4 November 2021.
  7. "Molnupiravir capsule". DailyMed. Retrieved 4 January 2022.
  8. 1 2 3 4 5 6 7 8 9 "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. Retrieved 23 December 2021.PD-icon.svgThis article incorporates text from this source, which is in the public domain .
  9. O'Shaughnessy JA (22 March 2022). "Emergency Use Authorization 108". Letter to Merck Sharp & Dohme Corp. U.S. Food and Drug Administration (FDA).
  10. 1 2 3 4 5 6 "Fact sheet for healthcare providers: Emergency Use Authorization for molnupiravir" (PDF). Merck & Co., Inc. 23 December 2021. Archived from the original on 24 December 2021.
  11. 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.
  12. 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.
  13. 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 .
  14. 1 2 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.
  15. 1 2 3 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.
  16. 1 2 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.
  17. 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.
  18. 1 2 "First oral antiviral for COVID-19, Lagevrio (molnupiravir), approved by MHRA" (Press release). Medicines and Healthcare products Regulatory Agency (MHRA). 4 November 2021.
  19. "Merck and Ridgeback's Molnupiravir, an Oral COVID-19 Antiviral Medicine, Receives First Authorization in the World". Merck (Press release). 4 November 2021. Retrieved 4 November 2021.
  20. Robbins R, Khan AJ, Specia M (4 November 2021). "Britain Becomes First to Authorize an Antiviral Pill for Covid-19" . The New York Times . Retrieved 27 November 2021.{{cite news}}: CS1 maint: url-status (link)
  21. Kimball S (30 November 2021). "FDA advisory panel narrowly endorses Merck's oral Covid treatment pill, despite reduced efficacy and safety questions". CNBC. Retrieved 1 January 2022.
  22. 1 2 Lin MZ (24 December 2021). "A new drug to treat covid could create a breeding ground for mutant viruses". The Washington Post .
  23. 1 2 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 .
  24. 1 2 Lowe D (13 October 2021). "Molnupiravir mutations". Science (blog).
  25. Painter WP, Holman W, Bush JA, Almazedi F, Malik H, Eraut NC, et al. (March 2021). "Human safety, tolerability, and pharmacokinetics of molnupiravir, a novel broad-spectrum oral antiviral agent with activity against SARS-CoV-2". Antimicrobial Agents and Chemotherapy. 65 (5). doi:10.1128/AAC.02428-20. PMC   8092915 . PMID   33649113.
  26. Amara A, Penchala SD, Else L, Hale C, FitzGerald R, Walker L, et al. (September 2021). "The development and validation of a novel LC-MS/MS method for the simultaneous quantification of Molnupiravir and its metabolite ß-d-N4-hydroxycytidine in human plasma and saliva". Journal of Pharmaceutical and Biomedical Analysis. 206: 114356. doi:10.1016/j.jpba.2021.114356. PMC   7611757 . PMID   34509661. S2CID   237493842.
  27. 1 2 3 Mole B (October 2021). "Meet molnupiravir, Merck's Thor-inspired pill that hammers COVID". Ars Technica . Retrieved 2 October 2021.
  28. 1 2 3 Malone B, Campbell EA (September 2021). "Molnupiravir: coding for catastrophe". Nature Structural & Molecular Biology. 28 (9): 706–708. doi: 10.1038/s41594-021-00657-8 . PMID   34518697. S2CID   237507937.
  29. 1 2 USapplication 20200276219,Painter GR, Bluemling GR, Natchus MG, Guthrie D,"N4-hydroxycytidine and derivatives and anti-viral uses related thereto",published 2020-09-03, assigned to Emory University
  30. Wruhs O (1986). "[Comparative study of stability following the nailing of fractures of the femur shaft. An experimental study with cadaver bones]". Wiener Klinische Wochenschrift. Supplementum (in German). 169: 3–16. PMID   3464133.
  31. 1 2 3 4 5 Halford B. "An emerging antiviral takes aim at COVID-19". C&EN. Retrieved 2 October 2021.
  32. Cox RM, Wolf JD, Plemper RK (January 2021). "Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets". Nature Microbiology. 6 (1): 11–18. doi: 10.1038/s41564-020-00835-2 . PMC   7755744 . PMID   33273742.
  33. CDER Scientific Review Supporting EUA (PDF) (Report). Center for Drug Evaluation and Research.
  34. "The Medicines Patent Pool (MPP) and Merck Enter Into License Agreement for Molnupiravir, an Investigational Oral Antiviral COVID-19 Medicine, to Increase Broad Access in Low- and Middle-Income Countries". Merck (Press release). Retrieved 28 October 2021.
  35. "Merck Will Share Formula for Its Covid Pill With Poor Countries" . The New York Times . 27 October 2021. Retrieved 27 November 2021.{{cite web}}: CS1 maint: url-status (link)
  36. "Merck and Ridgeback Announce Submission of Emergency Use Authorization Application to the U.S. FDA for Molnupiravir, an Investigational Oral Antiviral Medicine, for the Treatment of Mild-to-Moderate COVID-19 in At Risk Adults". Merck (Press release). Retrieved 17 October 2021.
  37. "FDA to Hold Advisory Committee Meeting to Discuss Merck and Ridgeback's EUA Application for COVID-19 Oral Treatment". U.S. Food and Drug Administration (FDA) (Press release). 18 October 2021. Retrieved 19 October 2021.
  38. 1 2 Hensley, Scott (30 November 2021). "An FDA panel supports Merck COVID drug in mixed vote". NPR.
  39. "COVID-19: EMA starts rolling review of molnupiravir". European Medicines Agency (EMA). 25 October 2021. Retrieved 6 November 2021.
  40. Reed J (4 November 2021). "First pill to treat Covid gets approval in UK". BBC News Online . Retrieved 4 November 2021.
  41. Whipple T (4 November 2021). "UK first to approve 'game-changing' antiviral Covid pill" . The Times. Retrieved 5 November 2021.
  42. "Oral medicine for Covid-19 now available in Bangladesh". The Business Standard. 9 November 2021. Retrieved 10 November 2021.
  43. "Eskayef's Covid pill hits market". The Daily Star. 10 November 2021. Retrieved 10 November 2021.
  44. World Health Organization (2021). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 85" (PDF). WHO Drug Information. 35 (1).
  45. World Health Organization (2022). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 87" (PDF). WHO Drug Information. 36 (1).
  46. Kimball S (30 November 2021). "FDA advisory panel narrowly endorses Merck's oral Covid treatment pill, despite reduced efficacy and safety questions". CNBC. Retrieved 4 January 2022.
  47. Walker M (30 November 2021). "FDA Panel Narrowly Backs Merck's COVID Pill". MedPage Today. Retrieved 4 January 2022.
  48. Nelson CW, Otto SP (29 November 2021). "Mutagenic antivirals: the evolutionary risk of low doses". Virological. Retrieved 4 January 2022.
  49. Lovett S (11 December 2021). "Scientists' caution over use of new antiviral pill in immunosuppressed". The Independent. Retrieved 4 January 2022.
  50. "Merck and Ridgeback Biotherapeutics Provide Update on Progress of Clinical Development Program for Molnupiravir, an Investigational Oral Therapeutic for the Treatment of Mild-to-Moderate COVID-19". Merck (Press release). 15 April 2021. Retrieved 28 November 2021.
  51. Clinical trial number NCT04575597 for "Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adult Participants With COVID-19 (MK-4482-002)" at ClinicalTrials.gov
  52. "Merck and Ridgeback's Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study". Merck (Press release). 1 October 2021. Retrieved 28 November 2021.
  53. Herper M (1 October 2021). "Merck's antiviral pill reduces hospitalization of Covid patients, a possible game-changer for treatment". Stat . Retrieved 2 October 2021.
  54. Mishra M, Erman M (26 November 2021). "Merck's COVID-19 pill significantly less effective in new analysis". Reuters. Retrieved 2 December 2021.
  55. "NIHR funds community COVID-19 antiviral trial". NIHR. Retrieved 16 March 2022.
  56. "Thousands needed to try a new Covid antiviral treatment". BBC News. 25 January 2022. Retrieved 16 March 2022.

Further reading