NAV

Molnupiravir

Identification

Summary

Molnupiravir is an orally bioavailable isopropylester cytidine analog used to treat COVID-19.

Generic Name
Molnupiravir
DrugBank Accession Number
DB15661
Background

Molnupiravir (EIDD-2801, MK-4482) is the isopropylester prodrug of N4-hydroxycytidine.1,2 With improved oral bioavailability in non-human primates, it is hydrolyzed in vivo, and distributes into tissues where it becomes the active 5’-triphosphate form.2 The active drug incorporates into the genome of RNA viruses, leading to an accumulation of mutations known as viral error catastrophe.3 Recent studies have shown molnupiravir inhibits replication of human and bat coronaviruses, including SARS-CoV-2, in mice and human airway epithelial cells.1 A remdesivir resistant mutant mouse hepatitis virus has also been shown to have increased sensitivity to N4-hydroxycytidine.1

Molnupiravir was granted approval by the UK's Medicines and Health products Regulatory Agency (MHRA) on 4 November 2021 to prevent severe outcomes such as hospitalization and death due to COVID-19 in adults.5 Molnupiravir was also granted emergency use authorization by the FDA on December 23, 2021; however, it is not yet fully approved.7

Type
Small Molecule
Groups
Investigational
Structure
Similar Structures
Weight
Average: 329.309
Monoisotopic: 329.122299964
Chemical Formula
C13H19N3O7
Synonyms
  • Molnupiravir
External IDs
  • EIDD 1931-ISOPROPYL ESTER
  • EIDD-2801
  • MK-4482
  • WHO 11853
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Pharmacology

Indication

N4-hydroxycytidine and its prodrug molnupiravir are being studied for its activity against a number of viral infections including influenza, MERS-CoV, and SARS-CoV-2.1,3

Molnupiravir is approved in the UK for reducing the risk of hospitalization and death in mild to moderate COVID-19 cases for patients at increased risk of severe disease (eg. with obesity, diabetes mellitus, heart disease, or are over 60 years old).5,6

In the US, molnupiravir is authorized for emergency use for the treatment of high-risk adults With mild to moderate COVID-19.7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Prevention ofDeath••••••••••••••••••••• •• •••••• ••••••••••••••
Prevention ofHospitalizations••••••••••••••••••••• •• •••••• ••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

Molnupiravir is hydrolyzed in vivo to N4-hydroxycytidine, which is phosphorylated in tissue to the active 5’-triphosphate form, and incorporated into the genome of new virions, resulting in the accumulation of inactivating mutations, known as viral error catastrophe.1,3 A remdesivir resistant mutant mouse hepatitis virus has also been shown to have increased sensitivity to N4-hydroxycytidine.1

Absorption

After an 800 mg oral dose of molnupiravir every 12 hours, the active compound (N4-hydroxycytidine) reaches a Cmax of 2970 ng/mL, with a Tmax of 1.5 hours, and an AUC0-12h of 8360 h*ng/mL.6

Volume of distribution

Not Available

Protein binding

Molnupiravir and the active metabolite, N4-hydroxycytidine, are not protein bound in plasma.6

Metabolism

Molnupiravir is hydrolyzed to N4-hydroxycytidine, which distributes into tissues.2 Once inside cells, N4-hydroxycytidine is phosphorylated to the 5'-triphosphate form.2

Hover over products below to view reaction partners

Route of elimination

≤3% of an oral molnupiravir dose is eliminated in the urine as the active metabolite N4-hydroxycytidine.6

Half-life

The half life of the active metabolite, N4-hydroxycytidine, is 3.3 hours.6

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
  • Take with or without food. A high fat meal reduces the maximum concentration of the active metabolite by 35% and does not significantly affect the area under the curve.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LagevrioCapsule200 mg/1OralA-S Medication Solutions2021-12-23Not applicableUS flag
LagevrioCapsule200 mg/1OralMerck Sharp & Dohme Llc2021-12-23Not applicableUS flag

Categories

ATC Codes
J05AB18 — Molnupiravir
Drug Categories
Classification
Not classified
Affected organisms
  • Influenza Virus
  • SARS-CoV
  • SARS-CoV-2

Chemical Identifiers

UNII
YA84KI1VEW
CAS number
2349386-89-4
InChI Key
HTNPEHXGEKVIHG-QCNRFFRDSA-N
InChI
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
IUPAC Name
[(2R,3S,4R,5R)-3,4-dihydroxy-5-[(4Z)-4-(hydroxyimino)-2-oxo-1,2,3,4-tetrahydropyrimidin-1-yl]oxolan-2-yl]methyl 2-methylpropanoate
SMILES
CC(C)C(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=C\C(NC1=O)=N\O

References

General References
  1. T. P. Sheahan et al.: An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci. Transl. Med.. [Article]
  2. Toots M, Yoon JJ, Cox RM, Hart M, Sticher ZM, Makhsous N, Plesker R, Barrena AH, Reddy PG, Mitchell DG, Shean RC, Bluemling GR, Kolykhalov AA, Greninger AL, Natchus MG, Painter GR, Plemper RK: Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia. Sci Transl Med. 2019 Oct 23;11(515). pii: 11/515/eaax5866. doi: 10.1126/scitranslmed.aax5866. [Article]
  3. Hampton T: New Flu Antiviral Candidate May Thwart Drug Resistance. JAMA. 2020 Jan 7;323(1):17. doi: 10.1001/jama.2019.20225. [Article]
  4. DC Chemicals: EIDD-2081 MSDS [Link]
  5. GOV.UK: First oral antiviral for COVID-19 Lagevrio (molnupiravir), approved by MHRA [Link]
  6. Electronic Medicines Compendium: Lagevrio (Molnupiravir) 200mg Oral Capsules Summary of Product Characteristics [Link]
  7. Merck News Release: Merck and Ridgeback’s Molnupiravir Receives U.S. FDA Emergency Use Authorization for the Treatment of High-Risk Adults With Mild to Moderate COVID-19 [Link]
ChemSpider
84400552
BindingDB
429508
RxNav
2587901
Wikipedia
Molnupiravir

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
3CompletedPreventionCoronavirus Disease 2019 (COVID‑19)1
3CompletedTreatmentCoronavirus Disease 2019 (COVID‑19)1
3RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19)1
3RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19) / Severe Acute Respiratory Syndrome (SARS)1
3TerminatedTreatmentCoronavirus (SARS-CoV) / Coronavirus Disease 2019 (COVID‑19)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral200 mg/1
Capsule, coatedOral200 mg
Capsule, coatedOral20000000 mg
CapsuleOral200 MG
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility5.77 mg/mLALOGPS
logP-1.5ALOGPS
logP-0.36Chemaxon
logS-1.8ALOGPS
pKa (Strongest Acidic)8.21Chemaxon
pKa (Strongest Basic)-3.7Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count7Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area140.92 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity74.74 m3·mol-1Chemaxon
Polarizability31.66 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0911000000-8d2af023803f9d30ce04
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-06vl-1396000000-39b65250eb11f172e560
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-2920000000-164670a14e3b229fd344
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00du-9160000000-ecfc316c5b2f16bd759b
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-4921000000-55e7baa604397170aba4
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9450000000-48bc5d11e322ecf280f2
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Drug created at April 07, 2020 02:15 / Updated at February 03, 2022 06:26