Evidence map›Paper›PMID 32869033›Full record

ArticlebioRxiv : the preprint server for biology2021

Rethinking Remdesivir: Synthesis, Antiviral Activity and Pharmacokinetics of Oral Lipid Prodrugs.

Robert T Schooley, Aaron F Carlin, James R Beadle, Nadejda Valiaeva, Xing-Quan Zhang, Alex E Clark, Rachel E McMillan, Sandra L Leibel, Rachael N McVicar, Jialei Xie and 4 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 24 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Robert T Schooley *Division of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
Aaron F Carlin *Division of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
James R BeadleDivision of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
Nadejda ValiaevaDivision of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
Xing-Quan ZhangDivision of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
Alex E ClarkDivision of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
Rachel E McMillanDivision of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
Sandra L LeibelDepartment of Pediatrics, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
Rachael N McVicarSanford Consortium for Regenerative Medicine, La Jolla, CA, USA.
Jialei XieDivision of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
Aaron F GarretsonDivision of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
Victoria I SmithDivision of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
Joyce MurphyDivision of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
Karl Y HostetlerDivision of Infectious Diseases and Global Public Health, University of California San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.
University of California San Diego · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

Development of Sustained-Release Anti-HIV Nucleoside Phosphonate NanoparticlesR01AI131424 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SCHOOLEY, ROBERT TURNER · 2017 to 2021
$3.8M
Deconvolution of pro- and anti-viral responses to Dengue virus and Zika Virus infectionsK08AI130381 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CARLIN, AARON F. · 2019 to 2023
$1.0M
NIAID NIH HHS K08 AI130381NIAID NIH HHS R01 AI131424
6 · The paper itself

Abstract

Remdesivir (RDV, GS-5734) is currently the only FDA-approved antiviral drug for the treatment of SARS CoV-2 infection. The drug is approved for use in adults or children 12-years or older who are hospitalized for the treatment of COVID-19 on the basis of an acceleration of clinical recovery for inpatients with this disease. Unfortunately, the drug must be administered intravenously, restricting its use to those requiring hospitalization for relatively advanced disease. RDV is also unstable in plasma and has a complex activation pathway which may contribute to its highly variable antiviral efficacy in SARS-CoV-2 infected cells. Potent orally bioavailable antiviral drugs for early treatment of SARS-CoV-2 infection are urgently needed and several including molnupiravir and PF-07321332 are currently in clinical development. We focused on making simple, orally bioavailable lipid analogs of Remdesivir nucleoside (RVn, GS-441524) that are processed to RVn-monophosphate, the precursor of the active RVn-triphosphate, by a single-step intracellular cleavage. In addition to high oral bioavailability, stability in plasma and simpler metabolic activation, new oral lipid prodrugs of RVn had submicromolar anti-SARS-CoV-2 activity in a variety of cell types including Vero E6, Calu-3, Caco-2, human pluripotent stem cell (PSC)-derived lung cells and Huh7.5 cells. In Syrian hamsters oral treatment with ODBG-P-RVn was well tolerated and achieved therapeutic levels in plasma above the EC

Indexed as

antiviral agentsCaco-2 cellsCalu-3 cellsHuh7.5 cells and PSC-derived human lung cellslipid prodrugsRemdesivirRemdesivir nucleosideSARS-CoV-2Vero E6 cells

Identifiers

PMID32869033
PMCPMC7457622
OpenAlexW3080205372

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.