ArticleCommunications medicine2023
Transporter modulation of molnupiravir and its metabolite β-D-N4-hydroxycytidine across the blood-brain barrier in a rat.
Article in Communications medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Modeling blood-brain barrier-glioblastoma interactions: implications for chemoresistance and therapeutic targeting.Fluids and barriers of the CNS · 2026Review
- Anti-SARS-CoV-2 VHH and C7C peptide fused with Angiopep-2 efficiently traverse blood-brain barrier model and neutralizes virus.Frontiers in microbiology · 2026Article
- Evaluation of the course of improvement with molnupiravir treatment for feline infectious peritonitis.The Canadian veterinary journal = La revue veterinaire canadienne · 2025Article
- Efficacy of late-onset antiviral treatment in immunocompromised hosts with persistent SARS-CoV-2 infection.Journal of virology · 2024Article
- COVID-19 therapeutics.Clinical microbiology reviews · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe antiviral drug molnupiravir is an orally bioavailable prodrug of the nucleoside analog β-D-N4-hydroxycytidine (NHC), which is used to treat coronavirus disease 2019 (COVID-19). However, there is very little information on the barrier distribution of molnupiravir. Our hypothesis is that molnupiravir and NHC can penetrate the blood‒brain barrier (BBB) into brain tissue and that nucleoside transporters (equilibrative nucleoside transporters; ENT and concentrative nucleoside transporters; CNT) can modulate this process.
methodsTo investigate the mechanism of molnupiravir transport through the BBB, multiple microdialyses coupled to a validated ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC‒MS/MS) was developed to monitor dialysates, and nitrobenzylthioinosine (NBMPR; an inhibitor of ENT) was administered concomitantly with molnupiravir (100 mg/kg, i.v.) in the male rat.
resultsHere, we show that molnupiravir is rapidly metabolized to NHC in the blood and crossed the BBB in 20 min. Furthermore, when NBMPR is concomitantly administered to inhibit efflux, the concentrations of molnupiravir and NHC in the brain increased significantly.
conclusionsIn summary, molnupiravir rapidly transforms into NHC and crosses the BBB and reaches the brain at approximately 0.3-0.8% of the blood‒brain ratio. The maximum concentration of NHC in the blood and brain is above the average half maximal inhibitory concentration (IC50) of the drug required to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, suggesting a therapeutic effect. The penetration of NHC is modulated by NBMPR. These findings provide constructive information on brain disorders in clinical patients with COVID-19.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.