Molnupiravir

In the UK, molnupiravir is indicated for treatment of mild to moderate COVID{{nbhyph}}19 in adults with a positive SARS-COV-2 diagnostic test and who have at least one risk factor for developing severe illness.

In the US molnupiravir is unapproved but is authorized under an EUA for emergency use for the treatment of adults with mild-to-moderate COVID{{nbhyph}}19 who are at high risk for progression to severe COVID{{nbhyph}}19, including hospitalization or death, and for whom alternative COVID{{nbhyph}}19 treatment options approved or authorized by FDA are not accessible or clinically appropriate.{{cite web |title=Fact sheet for healthcare providers: Emergency Use Authorization for molnupiravir |website=U.S. Food and Drug Administration (FDA) |date=23 October 2023 |url=https://www.fda.gov/media/155054/download |format=PDF |access-date=14 January 2024 |archive-url=https://web.archive.org/web/20240114012408/https://www.fda.gov/media/155054/download |archive-date=14 January 2024 |url-status=live | publisher=Merck & Co., Inc. }}

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

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.

The US FDA prescription label contains a boxed warning.

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

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

Based on limited available data, there are no drug interactions.

Molnupiravir inhibits viral reproduction by promoting widespread mutations in the replication of viral RNA by RNA-directed RNA polymerase.{{cite journal|vauthors=Lowe D|date=13 October 2021|title=Molnupiravir mutations|url=https://www.science.org/content/blog-post/molnupiravir-mutations|journal=Science|type=blog|access-date=13 October 2021|archive-date=21 December 2021|archive-url=https://web.archive.org/web/20211221012428/https://www.science.org/content/blog-post/molnupiravir-mutations|url-status=live}} 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).{{cite journal | vauthors = Painter WP, Holman W, Bush JA, Almazedi F, Malik H, Eraut NC, Morin MJ, Szewczyk LJ, Painter GR | title = Human safety, tolerability, and pharmacokinetics of molnupiravir, a novel broad-spectrum oral antiviral agent with activity against SARS-CoV-2 | journal = Antimicrobial Agents and Chemotherapy | volume = 65 | issue = 5 | date = March 2021 | pmid = 33649113 | pmc = 8092915 | doi = 10.1128/AAC.02428-20 }}{{cite journal | vauthors = Amara A, Penchala SD, Else L, Hale C, FitzGerald R, Walker L, Lyons R, Fletcher T, Khoo S | title = The development and validation of a novel LC-MS/MS method for the simultaneous quantification of Molnupiravir and its metabolite β-d-N4-hydroxycytidine in human plasma and saliva | journal = Journal of Pharmaceutical and Biomedical Analysis | volume = 206 | page = 114356 | date = September 2021 | pmid = 34509661 | pmc = 7611757 | doi = 10.1016/j.jpba.2021.114356 | s2cid = 237493842 }}{{cite web |vauthors=Mole B |title=Meet molnupiravir, Merck's Thor-inspired pill that hammers COVID |url=https://arstechnica.com/science/2021/10/meet-molnupiravir-mercks-thor-inspired-pill-that-hammers-covid/ |website=Ars Technica |date=October 2021 |access-date=2 October 2021 |archive-date=2 October 2021 |archive-url=https://web.archive.org/web/20211002014152/https://arstechnica.com/science/2021/10/meet-molnupiravir-mercks-thor-inspired-pill-that-hammers-covid/ |url-status=live }} During replication, the virus's enzyme incorporates NHC-TP into newly made RNA instead of using real cytidine.

File:Molnupiravir metabolism.svg

Molnupiravir can swap between two forms (tautomers), one of which mimics cytidine (C) and the other uridine (U).{{cite journal | vauthors = Malone B, Campbell EA | title = Molnupiravir: coding for catastrophe | journal = Nature Structural & Molecular Biology | volume = 28 | issue = 9 | pages = 706–708 | date = September 2021 | pmid = 34518697 | doi = 10.1038/s41594-021-00657-8 |doi-access=free | s2cid = 237507937 }} NHC-TP is not recognized as an error by the virus's 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.

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The first synthesis of molnupiravir was disclosed in a patent filed by Emory University in 2018.{{cite patent |country=US |number=20200276219 |status=application |url=https://patents.google.com/patent/US20200276219A1/en?oq=US20200276219 |pubdate=2020-09-03 |fdate=2018-12-07 |pridate=2017-12-07 |inventor=Painter GR, Bluemling GR, Natchus MG, Guthrie D |title=N4-hydroxycytidine and derivatives and anti-viral uses related thereto |assign1=Emory University }} {{Webarchive|url=https://web.archive.org/web/20211005163534/https://patents.google.com/patent/US20200276219A1/en?oq=US20200276219 |date=5 October 2021 }}

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.{{rp|93–95}}

:File:Molnupiravir synthesis.svg

Molnupiravir was developed at Emory University by its drug innovation company, Drug Innovation Ventures at Emory (DRIVE). 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.{{Unreliable medical source|date=April 2022}} When turned into the prodrug EIDD-2801 (molnupiravir), the compound also showed activity against other RNA viruses including influenza, Ebola, chikungunya, and various coronaviruses.{{cite web |vauthors=Halford B |title=An emerging antiviral takes aim at COVID-19 |url=https://cen.acs.org/pharmaceuticals/drug-development/emerging-antiviral-takes-aim-COVID-19/98/web/2020/05 |website=Chemical & Engineering News |access-date=2 October 2021 |archive-date=2 August 2020 |archive-url=https://web.archive.org/web/20200802021321/https://cen.acs.org/pharmaceuticals/drug-development/emerging-antiviral-takes-aim-COVID-19/98/web/2020/05 |url-status=live }}

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.

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

In March 2020, the research team pivoted to studying SARS-CoV-2, and successfully used molnupiravir to treat human cells infected with the novel coronavirus.{{Unreliable medical source|date=April 2022}} A study found that it is orally active against SARS-CoV-2 in ferrets.{{cite journal | vauthors = Cox RM, Wolf JD, Plemper RK | title = Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets | journal = Nature Microbiology | volume = 6 | issue = 1 | pages = 11–18 | date = January 2021 | pmid = 33273742 | pmc = 7755744 | doi = 10.1038/s41564-020-00835-2 | doi-access = free | title-link = doi }}

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

The primary data supporting the US 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{{nbhyph}}19 at high risk for progression to severe COVID{{nbhyph}}19 and/or hospitalization.{{cite report | url=https://www.fda.gov/media/155241/download | format=PDF | title=CDER Scientific Review Supporting EUA | publisher=Center for Drug Evaluation and Research | date= | access-date=16 February 2022 | archive-date=16 February 2022 | archive-url=https://web.archive.org/web/20220216041421/https://www.fda.gov/media/155241/download | url-status=live }} Participants were adults 18 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{{nbhyph}}19 vaccine. 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. Of the 709 people who received molnupiravir, 6.8% were hospitalized or died within this period compared to 9.7% of the 699 people who received a placebo.

In November 2022, the British National Institute for Health and Care Excellence decided molnupiravir should not be routinely used to treat COVID{{nbhyph}}19, as research showed it made no significant difference to hospitalization or death rates and was not cost effective. The drug was added to its "not recommended" list in draft COVID{{nbhyph}}19 treatment guidance for consultation.{{cite news |url=https://www.telegraph.co.uk/news/2023/02/11/almost-1bn-spent-anti-covid-drug-doesnt-work/ |title=Almost £1bn spent on anti-Covid drug that makes 'no significant difference' | vauthors = Donnelly L |newspaper=The Daily Telegraph |url-access=limited |date=11 February 2023 |access-date=13 February 2023}}{{cite web |url=https://www.nice.org.uk/news/article/nice-recommends-3-treatments-for-covid-19-in-draft-guidance |title=NICE recommends 3 treatments for COVID-19 in draft guidance |website=National Institute for Health and Care Excellence (NICE) |date=16 November 2022 |access-date=13 February 2023}}

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{{nbhyph}}19 oral medication to 105 low- and middle-income countries. The cost of the US government's initial purchase was about $712 per course of treatment; treatment with generics in developing countries can cost as little as $20.{{cite press release|title=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|url=https://www.merck.com/news/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-countri/|access-date=28 October 2021|website=Merck & Co.|archive-date=27 October 2021|archive-url=https://web.archive.org/web/20211027235339/https://www.merck.com/news/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-countri/|url-status=live}}{{cite web | title=Merck Will Share Formula for Its Covid Pill With Poor Countries | website=The New York Times | date=27 October 2021 | url=https://www.nytimes.com/2021/10/27/health/covid-pill-access-molnupiravir.html | url-access=limited | access-date=27 November 2021 | url-status=live | archive-date=27 November 2021 | archive-url=https://web.archive.org/web/20211127084355/https://www.nytimes.com/2021/10/27/health/covid-pill-access-molnupiravir.html }}

Sales of molnupiravir were $952 million in the fourth quarter of 2021.{{cite news | vauthors = Erman M |title=Merck sees 2022 sales up nearly 20%, mostly on molnupiravir |url=https://www.reuters.com/business/merck-sees-2022-sales-up-nearly-20-mostly-molnupiravir-2022-02-03/ |access-date=29 October 2022 |work=Reuters |date=3 February 2022 }}

In October 2021, Merck submitted an EUA application to the FDA, and in November 2021, the FDA's Antimicrobial Drugs Advisory Committee (AMDAC) at the Center for Drug Evaluation and Research met to discuss the application.{{cite press release|title=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|url=https://www.merck.com/news/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-c/|access-date=17 October 2021|website=Merck & Co.|archive-date=17 October 2021|archive-url=https://web.archive.org/web/20211017142802/https://www.merck.com/news/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-c/|url-status=live}}{{cite press release|date=18 October 2021|title=FDA to Hold Advisory Committee Meeting to Discuss Merck and Ridgeback's EUA Application for COVID-19 Oral Treatment|url=https://www.fda.gov/news-events/press-announcements/fda-hold-advisory-committee-meeting-discuss-merck-and-ridgebacks-eua-application-covid-19-oral|access-date=19 October 2021|website=U.S. Food and Drug Administration (FDA)|archive-date=18 October 2021|archive-url=https://web.archive.org/web/20211018220538/https://www.fda.gov/news-events/press-announcements/fda-hold-advisory-committee-meeting-discuss-merck-and-ridgebacks-eua-application-covid-19-oral|url-status=live}} 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{{nbhyph}}19.{{cite web|url=https://www.npr.org/sections/health-shots/2021/11/30/1060130774/an-fda-panel-supports-merck-covid-drug-in-mixed-vote|title=An FDA panel supports Merck COVID drug in mixed vote| vauthors = Hensley S |date=30 November 2021|website=NPR|access-date=3 December 2021|archive-date=4 January 2022|archive-url=https://web.archive.org/web/20220104210958/https://www.npr.org/sections/health-shots/2021/11/30/1060130774/an-fda-panel-supports-merck-covid-drug-in-mixed-vote|url-status=live}} Concerns were expressed over the drug's low effectiveness in preventing death, which in the final trial was only 30%, as well as the increased mutation rate the drug causes, which could theoretically worsen the pandemic by driving the evolution of more dangerous variants. In December 2021, the US Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for molnupiravir for the treatment of mild-to-moderate COVID{{nbhyph}}19 in adults with positive results of direct SARS-CoV-2 viral testing who are at high risk for progression to severe COVID{{nbhyph}}19, including hospitalization or death, and for whom alternative COVID{{nbhyph}}19 treatment options authorized by the FDA are not accessible or clinically appropriate.

In October 2021, the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) started a rolling review of molnupiravir.{{cite web | title=COVID-19: EMA starts rolling review of molnupiravir | website=European Medicines Agency (EMA) | date=25 October 2021 | url=https://www.ema.europa.eu/en/news/covid-19-ema-starts-rolling-review-molnupiravir | access-date=6 November 2021 | archive-date=4 November 2021 | archive-url=https://web.archive.org/web/20211104160832/https://www.ema.europa.eu/en/news/covid-19-ema-starts-rolling-review-molnupiravir | url-status=live }} In February 2023, the EMA recommended the refusal of the marketing authorization for molnupiravir.{{Cite web |url=https://www.ema.europa.eu/en/documents/smop-initial/questions-and-answers-refusal-marketing-authorisation-lagevrio-molnupiravir_en.pdf |title=Refusal of the marketing authorisation for Lagevrio (molnupiravir) |access-date=14 January 2024 |archive-date=14 January 2024 |archive-url=https://web.archive.org/web/20240114124232/https://www.ema.europa.eu/en/documents/smop-initial/questions-and-answers-refusal-marketing-authorisation-lagevrio-molnupiravir_en.pdf |url-status=live }} In June 2023, Merck Sharp & Dohme withdrew its application for a marketing authorization of molnupiravir.{{cite web | website=European Medicines Agency (EMA) | title=Lagevrio EPAR | date=21 June 2023 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lagevrio | access-date=14 January 2024 | archive-date=14 January 2024 | archive-url=https://web.archive.org/web/20240114124229/https://www.ema.europa.eu/en/medicines/human/EPAR/lagevrio | url-status=live }}

In 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{{nbhyph}}19. The MHRA issued a conditional marketing authorization applicable in the UK, and an emergency use authorization for Northern Ireland.{{cite web |url=https://www.bbc.co.uk/news/health-59163899 |title=First pill to treat Covid gets approval in UK |date=4 November 2021 |vauthors=Reed J |website=BBC News Online |access-date=4 November 2021 |archive-date=4 November 2021 |archive-url=https://web.archive.org/web/20211104111147/https://www.bbc.co.uk/news/health-59163899 |url-status=live }}{{cite news |vauthors=Whipple T |title=UK first to approve 'game-changing' antiviral Covid pill |url=https://www.thetimes.com/uk/healthcare/article/molnupiravir-antiviral-covid-pill-approved-by-uk-regulator-9n5bgql9d |access-date=5 November 2021 |work=The Times |date=4 November 2021 |url-access=subscription |archive-date=4 November 2021 |archive-url=https://web.archive.org/web/20211104222338/https://www.thetimes.co.uk/article/molnupiravir-antiviral-covid-pill-approved-by-uk-regulator-9n5bgql9d |url-status=live }}

In November 2021, the Bangladesh Directorate General of Drug Administration (DGDA) authorized emergency use of molnupiravir.{{cite news|title=Oral medicine for Covid-19 now available in Bangladesh|url=https://www.tbsnews.net/bangladesh/health/eskayef-square-get-dgda-approval-produce-covid-19-drug-molnupiravir-327271|newspaper=The Business Standard|date=9 November 2021|access-date=10 November 2021|archive-date=10 November 2021|archive-url=https://web.archive.org/web/20211110102039/https://www.tbsnews.net/bangladesh/health/eskayef-square-get-dgda-approval-produce-covid-19-drug-molnupiravir-327271|url-status=live}}{{cite news|title=Eskayef's Covid pill hits market|url=https://www.thedailystar.net/health/disease/coronavirus/news/eskayefs-covid-pill-hits-market-2226206|date=10 November 2021|access-date=10 November 2021|newspaper=The Daily Star|archive-date=9 November 2021|archive-url=https://web.archive.org/web/20211109195714/https://www.thedailystar.net/health/disease/coronavirus/news/eskayefs-covid-pill-hits-market-2226206|url-status=live}}

In January 2022, molnupiravir was approved for medical use in Israel{{cite web|url=https://www.gov.il/en/departments/news/02012022-02|title=The Anti-Viral Drug Lagevrio (Molnupiravir) for the Treatment of COVID-19 Has Been Approved|access-date=30 June 2022|archive-date=4 July 2022|archive-url=https://web.archive.org/web/20220704045603/https://www.gov.il/en/departments/news/02012022-02|url-status=live}} and in February 2022 in Russia.{{cite web | url = https://vademec.ru/news/2022/02/04/zaregistrirovan-peroralnyy-preparat-na-osnove-molnupiravira-ot-promomeda/ | title = | last = Prokhorchuk | first = Sofia | date = 4 February 2022 | website = Vademecum | language = ru | script-title = ru: «Промомед» зарегистрировал пероральный препарат MSD для терапии COVID-19 | trans-title = Promomed has registered an oral MSD drug for COVID-19 therapy | access-date = 22 November 2023 | archive-date = 14 January 2024 | archive-url = https://web.archive.org/web/20240114124301/https://vademec.ru/news/2022/02/04/zaregistrirovan-peroralnyy-preparat-na-osnove-molnupiravira-ot-promomeda/ | url-status = live }}

Molnupiravir is the international nonproprietary name.{{cite journal | vauthors = ((World Health Organization)) | year = 2021 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 85 | journal = WHO Drug Information | volume = 35 | issue = 1 | hdl = 10665/340684 | hdl-access = free | author-link = World Health Organization }}{{cite journal | vauthors = ((World Health Organization)) | year = 2022 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 87 | journal = WHO Drug Information | volume = 36 | issue = 1 | hdl = 10665/352794 | hdl-access = free | author-link = World Health Organization }}

Generic versions are available under the brand names Molulife (Mankind),{{cite web | url = https://economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/mankind-bdr-pharma-join-hands-to-launch-anti-covid-19-pill-molulife/articleshow/88564986.cms | title = Mankind, BDR Pharma join hands to launch anti COVID-19 pill Molulife | date = 29 December 2021 | website = The Economic Times | publisher = | access-date = 23 November 2023 | quote = | archive-date = 14 January 2024 | archive-url = https://web.archive.org/web/20240114124331/https://economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/mankind-bdr-pharma-join-hands-to-launch-anti-covid-19-pill-molulife/articleshow/88564986.cms | url-status = live }} Molena (Emcure),{{cite web | url = https://www.pharmaceutical-technology.com/uncategorized/coronavirus-company-news-summary-emcure-pharma-to-launch-molnupiravir-in-india-ascletis-expands-production-of-ritonavir-oral-pill/ | title = Coronavirus company news summary – Emcure Pharma to launch molnupiravir in India – Ascletis expands production of ritonavir oral pill | last = Priyan | first = Vishnu | date = 3 January 2022 | website = PharmaceuticalTechnology | publisher = | access-date = 23 November 2023 | quote = | archive-date = 14 January 2024 | archive-url = https://web.archive.org/web/20240114124223/https://www.pharmaceutical-technology.com/uncategorized/coronavirus-company-news-summary-emcure-pharma-to-launch-molnupiravir-in-india-ascletis-expands-production-of-ritonavir-oral-pill/ | url-status = live }} and Esplevir (Promomed).

At a November 2021 AMDAC meeting, multiple advisors raised the concern that molnupiravir could accelerate the emergence of variants of concern.{{cite web|vauthors=Kimball S|date=30 November 2021|title=FDA advisory panel narrowly endorses Merck's oral Covid treatment pill, despite reduced efficacy and safety questions|url=https://www.cnbc.com/2021/11/30/fda-advisory-panel-narrowly-endorses-mercks-oral-covid-treatment-pill-despite-reduced-efficacy.html|access-date=4 January 2022|website=CNBC|archive-date=1 January 2022|archive-url=https://web.archive.org/web/20220101141446/https://www.cnbc.com/2021/11/30/fda-advisory-panel-narrowly-endorses-mercks-oral-covid-treatment-pill-despite-reduced-efficacy.html|url-status=live}}{{cite web|vauthors=Walker M|date=30 November 2021|title=FDA Panel Narrowly Backs Merck's COVID Pill|url=https://www.medpagetoday.com/infectiousdisease/covid19/95944|access-date=4 January 2022|website=MedPage Today|archive-date=4 January 2022|archive-url=https://web.archive.org/web/20220104095835/https://www.medpagetoday.com/infectiousdisease/covid19/95944|url-status=live}} Other scientists raised similar concerns both before and after the meeting.{{cite web|vauthors=Nelson CW, Otto SP|date=29 November 2021|title=Mutagenic antivirals: the evolutionary risk of low doses|url=https://virological.org/t/mutagenic-antivirals-the-evolutionary-risk-of-low-doses/768|access-date=4 January 2022|website=Virological|archive-date=1 January 2022|archive-url=https://web.archive.org/web/20220101165014/https://virological.org/t/mutagenic-antivirals-the-evolutionary-risk-of-low-doses/768|url-status=live}}{{cite web|vauthors=Lovett S|date=11 December 2021|title=Scientists' caution over use of new antiviral pill in immunosuppressed|url=https://www.independent.co.uk/news/science/covid-antiviral-pill-immune-omicron-latest-b1973175.html|access-date=4 January 2022|website=The Independent|archive-date=4 January 2022|archive-url=https://web.archive.org/web/20220104095833/https://www.independent.co.uk/news/science/covid-antiviral-pill-immune-omicron-latest-b1973175.html|url-status=live}} These concerns were confirmed with the September 2023 publication of a study of 15 million global SARS-CoV-2 sequences: after molnupiravir had been introduced in 2022, genomic changes were more common, especially where it had been used.{{cite journal | vauthors = Sanderson T, Hisner R, Donovan-Banfield I, Hartman H, Løchen A, Peacock TP, Ruis C | title = A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes | journal = Nature | pages = 594–600 | date = September 2023 | volume = 623 | issue = 7987 | pmid = 37748513 | doi = 10.1038/s41586-023-06649-6 | pmc = 10651478 | bibcode = 2023Natur.623..594S | s2cid = 262748823 | doi-access = free }}

Alternative patented routes to molnupiravir have been reviewed.{{cite journal | vauthors = Wruhs O | title = [Comparative study of stability following the nailing of fractures of the femur shaft. An experimental study with cadaver bones] | language = German | journal = Wiener Klinische Wochenschrift. Supplementum | year = 1986 | volume = 169| issue = | pages = 3–16| pmid = 3464133}}

Molnupiravir has been investigated for potential to reduce the severity of COVID-19 symptoms, but no meaningful benefit was found.{{cite journal |vauthors=Huang J, Ma Q, Su Z, Cheng X |title=Advancements in the Development of Anti-SARS-CoV-2 Therapeutics |journal=Int J Mol Sci |volume=25 |issue=19 |date=October 2024 |page=10820 |pmid=39409149 |pmc=11477007 |doi=10.3390/ijms251910820 |doi-access=free |url=}}

{{Reflist}}

• {{cite journal |vauthors=Thorlund K, Sheldrick K, Meyerowitz-Katz G, Singh S, Hill A |title=Making Statistical Sense of the Molnupiravir MOVe-OUT Clinical Trial |journal=Am J Trop Med Hyg |volume= 106|issue= 5|pages= 1301–1304|date=March 2022 |pmid=35276667 |doi=10.4269/ajtmh.21-1339 |pmc=9128711 |s2cid=247406958 }}

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