Evidence map›Paper›PMID 37425890›Full record

ArticlebioRxiv : the preprint server for biology2023

Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential.

David R Martinez, Fernando R Moreira, Mark R Zweigart, Kendra L Gully, Gabriela De la Cruz, Ariane J Brown, Lily E Adams, Nicholas Catanzaro, Boyd Yount, Thomas J Baric and 20 more

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

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 11 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 3 institutions in 1 country.

David R MartinezDepartment of Immunobiology, Yale School of Medicine, New Haven, CT, 06510, USA.
Fernando R MoreiraDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Mark R ZweigartDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kendra L GullyDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Gabriela De la CruzLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Ariane J BrownDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lily E AdamsDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nicholas CatanzaroDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Boyd YountDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Thomas J BaricDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Michael L MalloryDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Helen ConradDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Samantha R MayDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Stephanie DongDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
D Trevor ScobeyDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Stephanie A MontgomeryDepartment of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Jason PerryGilead Sciences, Inc, Foster City, CA, USA.
Darius BabusisGilead Sciences, Inc, Foster City, CA, USA.
Kimberly T BarrettGilead Sciences, Inc, Foster City, CA, USA.
Anh-Hoa NguyenGilead Sciences, Inc, Foster City, CA, USA.
Anh-Quan NguyenGilead Sciences, Inc, Foster City, CA, USA.
Rao KallaGilead Sciences, Inc, Foster City, CA, USA.
Roy BannisterGilead Sciences, Inc, Foster City, CA, USA.
John P BilelloGilead Sciences, Inc, Foster City, CA, USA.
Joy Y FengGilead Sciences, Inc, Foster City, CA, USA.
Tomas CihlarGilead Sciences, Inc, Foster City, CA, USA.
Ralph S BaricDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Richard L MackmanGilead Sciences, Inc, Foster City, CA, USA.
Alexandra SchäferDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Timothy P SheahanDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
University of North Carolina at Chapel Hill · USGilead Sciences (United States) · USYale University · US

Funding

Research Project 1: Coronavirus antiviral lead development and combination testingU19AI171292 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S, WILLSON, TIMOTHY M · 2022 to 2022
$65.5M
Project 4 - Influenza - UABU19AI142759 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI WHITLEY, RICHARD J. · 2019 to 2023
$37.5M
Screening CoreU19AI109680 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MADDRY, JOSEPH A · 2014 to 2018
$34.9M
Broad-spectrum antiviral GS-5734 to treat MERS-CoV and related emerging CoVR01AI132178 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S, SHEAHAN, TIMOTHY PATRICK · 2017 to 2021
$7.0M
NIAID NIH HHS R01 AI132178NIAID NIH HHS U19 AI109680NIAID NIH HHS U19 AI142759NIAID NIH HHS U19 AI171292
6 · The paper itself

Abstract

Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, the emergence of SARS-CoV-2 variants of concern (VOC) that can partially evade vaccine immunity remains a global health concern. In addition, the emergence of highly mutated and neutralization-resistant SARS-CoV-2 VOCs such as BA.1 and BA.5 that can partially or fully evade (1) many therapeutic monoclonal antibodies in clinical use underlines the need for additional effective treatment strategies. Here, we characterize the antiviral activity of GS-5245, Obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved RNA-dependent viral RNA polymerase (RdRp). Importantly, we show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-related Bat-CoV RsSHC014, Middle East Respiratory Syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant in vitro and highly effective as antiviral therapy in mouse models of SARS-CoV, SARS-CoV-2 (WA/1), MERS-CoV and Bat-CoV RsSHC014 pathogenesis. In all these models of divergent coronaviruses, we observed protection and/or significant reduction of disease metrics such as weight loss, lung viral replication, acute lung injury, and degradation in pulmonary function in GS-5245-treated mice compared to vehicle controls. Finally, we demonstrate that GS-5245 in combination with the main protease (M

Indexed as

Antiviralsbroad-spectrum drugsGS-5245nirmatrelvirnucleosideobeldesiviroral antiviral drugspandemic preparednessPaxlovid™remdesivir

Identifiers

PMID37425890
PMCPMC10327034
OpenAlexW4382362676

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.