Evidence map›Paper›PMID 36297546›Full record

ArticlePharmaceutics2022

Lactoferrin Binding to SARS-CoV-2 Spike Glycoprotein Blocks Pseudoviral Entry and Relieves Iron Protein Dysregulation in Several In Vitro Models.

Antimo Cutone, Luigi Rosa, Maria Carmela Bonaccorsi di Patti, Federico Iacovelli, Maria Pia Conte, Giusi Ianiro, Alice Romeo, Elena Campione, Luca Bianchi, Piera Valenti and 2 more

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Effect of Iron on Viral Infections.Food and environmental virology · 2025
    Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. To Boost or to Reset: The Role of Lactoferrin in Energy Metabolism.International journal of molecular sciences · 2023
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
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

12 authors at 3 institutions in 1 country.

Antimo CutoneDepartment of Biosciences and Territory, University of Molise, 86090 Pesche, Italy.ORCID 0000-0002-7492-8616
Luigi RosaDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy.ORCID 0000-0002-1252-6080
Maria Carmela Bonaccorsi di PattiDepartment of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy.ORCID 0000-0002-4794-7037
Federico IacovelliDepartment of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.ORCID 0000-0001-7511-6575
Maria Pia ConteDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy.ORCID 0000-0003-0753-6003
Giusi IaniroDepartment of Biosciences and Territory, University of Molise, 86090 Pesche, Italy.ORCID 0000-0002-3033-8120
Alice RomeoDepartment of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.ORCID 0000-0001-6162-6814
Elena CampioneDermatology Unit, University of Rome "Tor Vergata", 00133 Rome, Italy.
Luca BianchiDermatology Unit, University of Rome "Tor Vergata", 00133 Rome, Italy.ORCID 0000-0001-8697-6896
Piera ValentiDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy.
Mattia FalconiDepartment of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.ORCID 0000-0002-3990-4758
Giovanni MusciDepartment of Biosciences and Territory, University of Molise, 86090 Pesche, Italy.
University of Rome Tor Vergata · ITSapienza University of Rome · ITUniversity of Molise · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

SARS-CoV-2 causes COVID-19, a predominantly pulmonary disease characterized by a burst of pro-inflammatory cytokines and an increase in free iron. The viral glycoprotein Spike mediates fusion to the host cell membrane, but its role as a virulence factor is largely unknown. Recently, the antiviral activity of lactoferrin against SARS-CoV-2 was demonstrated in vitro and shown to occur via binding to cell surface receptors, and its putative interaction with Spike was suggested by in silico analyses. We investigated the anti-SARS-CoV-2 activity of bovine and human lactoferrins in epithelial and macrophagic cells using a Spike-decorated pseudovirus. Lactoferrin inhibited pseudoviral fusion and counteracted the deleterious effects of Spike on iron and inflammatory homeostasis by restoring basal levels of iron-handling proteins and of proinflammatory cytokines IL-1β and IL-6. Using pull-down assays, we experimentally proved for the first time that lactoferrin binds to Spike, immediately suggesting a mechanism for the observed effects. The contribution of transferrin receptor 1 to Spike-mediated cell fusion was also experimentally demonstrated. In silico analyses showed that lactoferrin interacts with transferrin receptor 1, suggesting a multifaceted mechanism of action for lactoferrin. Our results give hope for the use of bovine lactoferrin, already available as a nutraceutical, as an adjuvant to standard therapies in COVID-19.

Indexed as

COVID-19inflammationiron homeostasislactoferrinSARS-CoV-2

Identifiers

PMID36297546
PMCPMC9612385
OpenAlexW4303962448

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Registered trials

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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.