Evidence map›Paper›PMID 35982678›Full record

ArticlebioRxiv : the preprint server for biology2022

Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors.

Seyed Arad Moghadasi, Emmanuel Heilmann, Ahmed Magdy Khalil, Christina Nnabuife, Fiona L Kearns, Chengjin Ye, Sofia N Moraes, Francesco Costacurta, Morgan A Esler, Hideki Aihara and 5 more

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

Article in bioRxiv : the preprint server for biology, 2022. 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, 42 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 4 countries.

Seyed Arad MoghadasiDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota - Twin Cities, Minneapolis, Minnesota, USA, 55455.
Emmanuel HeilmannInstitute of Virology, Medical University of Innsbruck, Innsbruck, Austria.
Ahmed Magdy KhalilTexas Biomedical Research Institute, San Antonio, Texas, USA, 78227.
Christina NnabuifeDepartment of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, Texas, USA, 77030.
Fiona L KearnsDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA, 92093.
Chengjin YeTexas Biomedical Research Institute, San Antonio, Texas, USA, 78227.
Sofia N MoraesDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota - Twin Cities, Minneapolis, Minnesota, USA, 55455.
Francesco CostacurtaInstitute of Virology, Medical University of Innsbruck, Innsbruck, Austria.
Morgan A EslerDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota - Twin Cities, Minneapolis, Minnesota, USA, 55455.
Hideki AiharaDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota - Twin Cities, Minneapolis, Minnesota, USA, 55455.
Dorothee von LaerInstitute of Virology, Medical University of Innsbruck, Innsbruck, Austria.
Luis Martinez-SobridoTexas Biomedical Research Institute, San Antonio, Texas, USA, 78227.
Timothy PalzkillDepartment of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, Texas, USA, 77030.
Rommie E AmaroDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA, 92093.
Reuben S HarrisDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota - Twin Cities, Minneapolis, Minnesota, USA, 55455.
University of Minnesota · USInnsbruck Medical University · ATTexas Biomedical Research Institute · USBaylor College of Medicine · USUniversity of California San Diego · US

Funding

Project 5: Pandemic Virus Helicase InhibitorsU19AI171954 · NIAID · UNIVERSITY OF MINNESOTA · PI Reuben S Harris, Fang Li · 2022 to 2026
$100.9M
NIAID NIH HHS U19 AI171954
6 · The paper itself

Abstract

Vaccines and drugs have helped reduce disease severity and blunt the spread of SARS-CoV-2. However, ongoing virus transmission, continuous evolution, and increasing selective pressures have the potential to yield viral variants capable of resisting these interventions. Here, we investigate the susceptibility of natural variants of the main protease (Mpro/3CLpro) of SARS-CoV-2 to protease inhibitors. Multiple single amino acid changes in Mpro confer resistance to nirmatrelvir (the active component of Paxlovid). An additional clinical-stage inhibitor, ensitrelvir (Xocova), shows a different resistance mutation profile. Importantly, phylogenetic analyses indicate that several of these resistant variants have pre-existed the introduction of these drugs into the human population and are capable of spreading. These results encourage the monitoring of resistance variants and the development of additional protease inhibitors and other antiviral drugs with different mechanisms of action and resistance profiles for combinatorial therapy.

Identifiers

PMID35982678
PMCPMC9387136
OpenAlexW4290694860

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.