Evidence map›Paper›PMID 36555153›Full record

ArticleInternational journal of molecular sciences2022

Exploring Highly Conserved Regions of SARS-CoV-2 Spike S2 Subunit as Targets for Fusion Inhibition Using Chimeric Proteins.

Daniel Polo-Megías, Mario Cano-Muñoz, Alberto G Berruezo, Géraldine Laumond, Christiane Moog, Francisco Conejero-Lara

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 32% of its field
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

2 citing papers in PubMed, 7 citations in OpenAlex.

  1. Journal of chemical information and modeling · 2025
    Article
  2. 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 at 2 institutions in 2 countries.

Daniel Polo-MegíasDepartamento de Química Física, Instituto de Biotecnología y Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente (UEQ), Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain.ORCID 0000-0002-4019-5506
Mario Cano-MuñozDepartamento de Química Física, Instituto de Biotecnología y Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente (UEQ), Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain.ORCID 0000-0003-0627-3379
Alberto G BerruezoDepartamento de Química Física, Instituto de Biotecnología y Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente (UEQ), Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain.
Géraldine LaumondLaboratoire d'ImmunoRhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1109, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, F-67000 Strasbourg, France.
Christiane MoogLaboratoire d'ImmunoRhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S 1109, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, F-67000 Strasbourg, France.ORCID 0000-0002-0916-156X
Francisco Conejero-LaraDepartamento de Química Física, Instituto de Biotecnología y Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente (UEQ), Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain.ORCID 0000-0002-8282-2168
Universidad de Granada · ESInserm · FR

Funding

Agence Nationale de Recherches sur le Sida et les Hépatites Virales ANR-10-LABX-77Agence Nationale de Recherches sur le Sida et les Hépatites Virales EHVA (N°681032, Horizon 2020)ERDF/ESF, "A way to make Europe"/"Investing in your future"Regional Government of Andalusia CV20.26565Spain's State Research Agency (SRA/10.13039/501100011033) PID2019.107515RB.C21
6 · The paper itself

Abstract

Since the beginning of the COVID-19 pandemic, considerable efforts have been made to develop protective vaccines against SARS-CoV-2 infection. However, immunity tends to decline within a few months, and new virus variants are emerging with increased transmissibility and capacity to evade natural or vaccine-acquired immunity. Therefore, new robust strategies are needed to combat SARS-CoV-2 infection. The viral spike composed of S1 and S2 subunits mediates viral attachment and membrane fusion to infect the host cell. In this process, interaction between the highly conserved heptad repeat 1 and 2 regions (HR1 and HR2) of S2 is crucial and for this reason; these regions are promising targets to fight SARS-CoV-2. Here, we describe the design and characterization of chimeric proteins that structurally imitate the S2 HR1 region in a trimeric coiled-coil conformation. We biophysically characterized the proteins and determined their capacity to bind the HR2 region, as well as their inhibitory activity of SARS-CoV-2 infection in vitro. HR1 mimetic proteins showed conformational heterogeneity and a propensity to form oligomers. Moreover, their structure is composed of subdomains with varied stability. Interestingly, the full HR1 proteins showed high affinity for HR2-derived peptides and SARS-CoV-2 inhibitory activity, whereas smaller proteins mimicking HR1 subdomains had a decreased affinity for their complementary HR2 region and did not inhibit the virus. The results provide insight into effective strategies to create mimetic proteins with broad inhibitory activity and therapeutic potential against SARS-CoV-2.

Indexed as

COVID-19SARS-CoV-2Amino Acid SequenceCOVID-19 VaccinesHumansMembrane GlycoproteinsPandemicsRecombinant Fusion ProteinsSpike Glycoprotein, CoronavirusViral Envelope ProteinsCOVID-19 VaccinesMembrane GlycoproteinsRecombinant Fusion ProteinsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Viral Envelope ProteinsantiviralscalorimetrycoronavirusCOVID-19inhibitorsprotein designprotein engineering

Identifiers

PMID36555153
PMCPMC9778920
OpenAlexW4311849736

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.