Molnupiravir
[CAS# 2349386-89-4]

Identification

• Classification: API >> Other chemicals
• Name: Molnupiravir
• Synonyms: [(2R,3S,4R,5R)-3,4-Dihydroxy-5-[4-(hydroxyamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methyl 2-methylpropanoate
• Molecular Formula: C₁₃H₁₉N₃O₇
• Molecular Weight: 329.31
• CAS Registry Number: 2349386-89-4
• EC Number: 859-180-1
• SMILES: CC(C)C(=O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=CC(=NC2=O)NO)O)O

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Index of refraction: 1.651 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS08 Danger
• Hazard Statements: H372
• Precautionary Statements: P260-P264-P270-P319-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315

Discovory and Applicatios

Molnupiravir is an orally bioavailable antiviral prodrug designed to inhibit the replication of RNA viruses by targeting viral RNA-dependent RNA polymerase. Its chemical structure consists of a nucleoside analogue in which a modified ribose sugar is linked to a pyrimidine base capable of tautomeric shifts that induce errors during viral RNA replication. The molecular formula of molnupiravir is C13H19N3O7, and it is administered as the prodrug, which is converted in vivo to its active form, β-D-N4-hydroxycytidine triphosphate. The active metabolite is incorporated into viral RNA, resulting in lethal mutagenesis and suppression of viral replication.

The discovery of molnupiravir was driven by the need for broad-spectrum antivirals effective against RNA viruses, including influenza, coronaviruses, and other emerging pathogens. The compound was originally developed from studies on ribonucleoside analogues and optimized to increase oral bioavailability and metabolic stability. Its prodrug design allows efficient absorption in the gastrointestinal tract, followed by enzymatic conversion to the active nucleoside analogue within host cells. This strategy improves pharmacokinetic properties and ensures adequate intracellular concentrations for antiviral activity.

Molnupiravir exerts its antiviral effect by mimicking cytidine and uridine during viral RNA synthesis. Viral RNA-dependent RNA polymerase incorporates the active nucleoside analogue into the growing RNA chain. Due to tautomeric shifts between the amino and imino forms of the nucleobase, the analogue can pair with both guanosine and adenosine, resulting in the accumulation of mutations in the viral genome. This process, known as viral error catastrophe or lethal mutagenesis, impairs viral replication and reduces viral load. The compound does not directly inhibit polymerase activity but instead relies on this mutagenic mechanism to suppress viral propagation.

The development of molnupiravir included extensive preclinical and clinical evaluation. In vitro studies demonstrated potent antiviral activity against multiple RNA viruses, including SARS-CoV-2, and in vivo studies confirmed reductions in viral titers and disease severity in animal models. Clinical trials in humans evaluated safety, pharmacokinetics, and efficacy, showing that oral administration of molnupiravir can reduce the risk of hospitalization and progression to severe disease in patients with early-stage viral infection. These trials established appropriate dosing regimens and identified potential adverse effects, which were generally mild and reversible.

From a chemical perspective, molnupiravir is a nucleoside prodrug with a hydroxylamine substitution on the cytidine base and esterification on the ribose moiety. The ester linkage is hydrolyzed by host esterases to release the active nucleoside, and further phosphorylation by host kinases generates the triphosphate form. The compound is soluble in aqueous and polar organic solvents, facilitating formulation as an oral dosage. Its stability under normal storage conditions supports distribution and shelf-life in pharmaceutical applications.

Molnupiravir has significant implications for public health due to its oral availability, broad-spectrum activity, and mechanism that reduces the likelihood of resistance development. Its use provides a convenient antiviral treatment option, particularly for early intervention during outbreaks of RNA virus infections. The ability to inhibit viral replication through mutagenesis rather than direct enzyme inhibition offers a complementary approach to other antiviral strategies, such as protease inhibitors or monoclonal antibodies.

Overall, molnupiravir is a chemically and pharmacologically engineered nucleoside prodrug that disrupts viral RNA replication through error-inducing incorporation into the genome. Its oral bioavailability, targeted activation, and broad-spectrum antiviral properties make it an important therapeutic agent for RNA virus infections. The compound exemplifies modern strategies in antiviral drug design, combining prodrug delivery, nucleoside chemistry, and mechanistic insight to achieve effective viral suppression.

References

2025. Real-world effectiveness and economic analysis of nirmatrelvir/ritonavir, remdesivir, and molnupiravir for treatment of COVID-19 among ambulatory patients in Thailand. Journal of Infection and Public Health.
DOI: 10.1016/j.jiph.2025.102826

2025. Electrochemical interpretations for the study of molnupiravir binding interactions with bovine serum albumin and DNA and molecular dynamics studies. Biochemical and Biophysical Research Communications.
DOI: 10.1016/j.bbrc.2025.151988