Molnupiravir

Identification

Summary

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

Generic Name
Molnupiravir
DrugBank Accession Number
DB15661
Background

Molnupiravir (EIDD-2801) 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

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

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

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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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.3 A remdesivir resistant mutant mouse hepatitis virus has also been shown to have increased sensitivity to N4-hydroxycytidine.1

Absorption

Molnupiravir is orally bioavailable in non-human primates.2

Volume of distribution

Not Available

Protein binding

Not Available

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

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Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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
No interactions found.

Categories

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]
ChemSpider
84400552
BindingDB
429508
Wikipedia
Molnupiravir

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingPreventionCoronavirus Disease 2019 (COVID‑19)1
2CompletedTreatmentCoronavirus Disease 2019 (COVID‑19)1
2RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19)1
2, 3Active Not RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19)1
2, 3TerminatedTreatmentCoronavirus Disease 2019 (COVID‑19)1
1CompletedTreatmentCoronavirus Disease 2019 (COVID‑19) / Infections, Coronavirus1
1, 2RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
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
Not Available

Drug created on April 07, 2020 02:15 / Updated on October 03, 2021 00:29