Evidence map›Paper›PMID 39660912›Full record

ArticlemSphere2025

Combined mutations in nonstructural protein 14, envelope, and membrane proteins mitigate the neuropathogenicity of SARS-CoV-2 Omicron BA.1 in K18-hACE2 mice.

Kotou Sangare, Shufeng Liu, Prabhuanand Selvaraj, Charles B Stauft, Matthew F Starost, Tony T Wang

Abstract read
In one paragraph

Article in mSphere, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Kotou Sangare *Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0002-6750-820X
Shufeng Liu *Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0001-9969-6041
Prabhuanand SelvarajDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0001-7266-3928
Charles B StauftDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0001-5633-2950
Matthew F StarostDivision of Veterinary Resources, Diagnostic and Research Services Branch, National Institutes of Health, Bethesda, Maryland, USA.
Tony T WangDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0001-8983-1721

Funding

HHS | U.S. Food and Drug Administration (FDA)
6 · The paper itself

Abstract

We previously reported that mutations outside the spike protein play a role in the attenuation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.1 variant in human ACE2 transgenic mice (K18-hACE2). Here, we assessed the pathogenicity of SARS-CoV-2 (WA1/2020) containing mutations from the Omicron BA.1 variant in K18-hACE2 mice. At an infection dose of 10 IMPORTANCE: Inoculation of transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) with SARS-CoV-2 often leads to a fatal brain infection. Omicron BA.1 variant, however, was found to be non-lethal in this model. Here, we systematically assessed the effect of individual mutations of Omicron BA.1 on the pathogenicity of the virus in hACE2 transgenic mice and found that combination of 5 mutations of Nsp14, E, and M of BA.1 variant significantly lowered brain viral load and reduced lethality. These results provide new insights into how SARS-CoV-2 Omicron BA.1 is attenuated.

Indexed as

COVID-19Membrane ProteinsMutationSARS-CoV-2Viral Envelope ProteinsViral Nonstructural ProteinsAngiotensin-Converting Enzyme 2AnimalsBrainDisease Models, AnimalHumansMiceMice, TransgenicSpike Glycoprotein, CoronavirusViral LoadACE2 protein, humanAce2 protein, mouseAngiotensin-Converting Enzyme 2Membrane ProteinsSpike Glycoprotein, CoronavirusViral Envelope ProteinsViral Nonstructural ProteinsCOVID-19Omicron BA.1SARS-CoV-2 variantsspike proteinSyrian hamsters

Identifiers

PMID39660912
PMCPMC11774043

What Socratic holds

Textmetadata
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 Socratic graph.