Lactoferrin Against SARS-CoV-2: In Vitro and In Silico Evidences
Lactoferrin (Lf) is a cationic glycoprotein synthetized by exocrine glands and is present in all human secretions. It is also secreted by neutrophils in infection and inflammation sites. This glycoprotein possesses antimicrobial activity due to its capability to chelate two ferric ions per molecule,...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2021-06-01
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Series: | Frontiers in Pharmacology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.666600/full |
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doaj-3ee752f6fe6546b78d8ca2bc6686c017 |
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language |
English |
format |
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DOAJ |
author |
Elena Campione Caterina Lanna Terenzio Cosio Luigi Rosa Maria Pia Conte Federico Iacovelli Alice Romeo Mattia Falconi Claudia Del Vecchio Elisa Franchin Maria Stella Lia Marilena Minieri Carlo Chiaramonte Marco Ciotti Marzia Nuccetelli Alessandro Terrinoni Ilaria Iannuzzi Luca Coppeda Andrea Magrini Sergio Bernardini Stefano Sabatini Felice Rosapepe Pier Luigi Bartoletti Nicola Moricca Andrea Di Lorenzo Massimo Andreoni Loredana Sarmati Alessandro Miani Prisco Piscitelli Piera Valenti Luca Bianchi |
spellingShingle |
Elena Campione Caterina Lanna Terenzio Cosio Luigi Rosa Maria Pia Conte Federico Iacovelli Alice Romeo Mattia Falconi Claudia Del Vecchio Elisa Franchin Maria Stella Lia Marilena Minieri Carlo Chiaramonte Marco Ciotti Marzia Nuccetelli Alessandro Terrinoni Ilaria Iannuzzi Luca Coppeda Andrea Magrini Sergio Bernardini Stefano Sabatini Felice Rosapepe Pier Luigi Bartoletti Nicola Moricca Andrea Di Lorenzo Massimo Andreoni Loredana Sarmati Alessandro Miani Prisco Piscitelli Piera Valenti Luca Bianchi Lactoferrin Against SARS-CoV-2: In Vitro and In Silico Evidences Frontiers in Pharmacology lactoferrin COVID-19 SARS-CoV-2 spike bovine lactoferrin |
author_facet |
Elena Campione Caterina Lanna Terenzio Cosio Luigi Rosa Maria Pia Conte Federico Iacovelli Alice Romeo Mattia Falconi Claudia Del Vecchio Elisa Franchin Maria Stella Lia Marilena Minieri Carlo Chiaramonte Marco Ciotti Marzia Nuccetelli Alessandro Terrinoni Ilaria Iannuzzi Luca Coppeda Andrea Magrini Sergio Bernardini Stefano Sabatini Felice Rosapepe Pier Luigi Bartoletti Nicola Moricca Andrea Di Lorenzo Massimo Andreoni Loredana Sarmati Alessandro Miani Prisco Piscitelli Piera Valenti Luca Bianchi |
author_sort |
Elena Campione |
title |
Lactoferrin Against SARS-CoV-2: In Vitro and In Silico Evidences |
title_short |
Lactoferrin Against SARS-CoV-2: In Vitro and In Silico Evidences |
title_full |
Lactoferrin Against SARS-CoV-2: In Vitro and In Silico Evidences |
title_fullStr |
Lactoferrin Against SARS-CoV-2: In Vitro and In Silico Evidences |
title_full_unstemmed |
Lactoferrin Against SARS-CoV-2: In Vitro and In Silico Evidences |
title_sort |
lactoferrin against sars-cov-2: in vitro and in silico evidences |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-06-01 |
description |
Lactoferrin (Lf) is a cationic glycoprotein synthetized by exocrine glands and is present in all human secretions. It is also secreted by neutrophils in infection and inflammation sites. This glycoprotein possesses antimicrobial activity due to its capability to chelate two ferric ions per molecule, as well as to interact with bacterial and viral anionic surface components. The cationic features of Lf bind to cells, protecting the host from bacterial and viral injuries. Its anti-inflammatory activity is mediated by the ability to enter inside the nucleus of host cells, thus inhibiting the synthesis of proinflammatory cytokine genes. In particular, Lf down-regulates the synthesis of IL-6, which is involved in iron homeostasis disorders and leads to intracellular iron overload, favoring viral replication and infection. The well-known antiviral activity of Lf has been demonstrated against DNA, RNA, and enveloped and naked viruses and, therefore, Lf could be efficient in counteracting also SARS-CoV-2 infection. For this purpose, we performed in vitro assays, proving that Lf exerts an antiviral activity against SARS-COV-2 through direct attachment to both SARS-CoV-2 and cell surface components. This activity varied according to concentration (100/500 μg/ml), multiplicity of infection (0.1/0.01), and cell type (Vero E6/Caco-2 cells). Interestingly, the in silico results strongly supported the hypothesis of a direct recognition between Lf and the spike S glycoprotein, which can thus hinder viral entry into the cells. These in vitro observations led us to speculate a potential supplementary role of Lf in the management of COVID-19 patients. |
topic |
lactoferrin COVID-19 SARS-CoV-2 spike bovine lactoferrin |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.666600/full |
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doaj-3ee752f6fe6546b78d8ca2bc6686c0172021-06-16T06:24:01ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-06-011210.3389/fphar.2021.666600666600Lactoferrin Against SARS-CoV-2: In Vitro and In Silico EvidencesElena Campione0Caterina Lanna1Terenzio Cosio2Luigi Rosa3Maria Pia Conte4Federico Iacovelli5Alice Romeo6Mattia Falconi7Claudia Del Vecchio8Elisa Franchin9Maria Stella Lia10Marilena Minieri11Carlo Chiaramonte12Marco Ciotti13Marzia Nuccetelli14Alessandro Terrinoni15Ilaria Iannuzzi16Luca Coppeda17Andrea Magrini18Sergio Bernardini19Stefano Sabatini20Felice Rosapepe21Pier Luigi Bartoletti22Nicola Moricca23Andrea Di Lorenzo24Massimo Andreoni25Loredana Sarmati26Alessandro Miani27Prisco Piscitelli28Piera Valenti29Luca Bianchi30Dermatology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Rome, ItalyDermatology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Rome, ItalyDermatology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Rome, ItalyDepartment of Public Health and Infectious Diseases, University of Rome “La Sapienza”, Rome, ItalyDepartment of Public Health and Infectious Diseases, University of Rome “La Sapienza”, Rome, ItalyDepartment of Biology, Structural Bioinformatics Group, University of Rome “Tor Vergata”, Rome, ItalyDepartment of Biology, Structural Bioinformatics Group, University of Rome “Tor Vergata”, Rome, ItalyDepartment of Biology, Structural Bioinformatics Group, University of Rome “Tor Vergata”, Rome, ItalyDepartment of Molecular Medicine, University of Padova, Padova, ItalyDepartment of Molecular Medicine, University of Padova, Padova, ItalyDepartment of Experimental Medicine, Tor Vergata University Hospital, Rome, ItalyDepartment of Experimental Medicine, Tor Vergata University Hospital, Rome, ItalyDepartment of Statistics, University of Rome Tor Vergata, Rome, ItalyVirology Unit, Tor Vergata University Hospital, Rome, ItalyLaboratory Medicine, Department of Experimental Medicine and Surgery, Tor Vergata University Hospital, Rome, ItalyDepartment of Experimental Medicine, Tor Vergata University Hospital, Rome, ItalyOccupational Medicine Department, University of Rome “Tor Vergata”, Rome, ItalyOccupational Medicine Department, University of Rome “Tor Vergata”, Rome, ItalyOccupational Medicine Department, University of Rome “Tor Vergata”, Rome, ItalyLaboratory Medicine, Department of Experimental Medicine and Surgery, Tor Vergata University Hospital, Rome, Italy0Villa dei Pini Hospital, Anzio, Italy1Pineta Grande Hospital, Caserta, Italy2Fimmg provincial, Rome, Italy0Villa dei Pini Hospital, Anzio, Italy3Infectious Disease Unit, Tor Vergata University Hospital, Rome, Italy3Infectious Disease Unit, Tor Vergata University Hospital, Rome, Italy3Infectious Disease Unit, Tor Vergata University Hospital, Rome, Italy4Department of Environmental Sciences and Policy, University of Milan, Milan, Italy5UNESCO Chair on Health Education and Sustainable Development, University of Naples Federico II, Naples, ItalyDepartment of Public Health and Infectious Diseases, University of Rome “La Sapienza”, Rome, ItalyDermatology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Rome, ItalyLactoferrin (Lf) is a cationic glycoprotein synthetized by exocrine glands and is present in all human secretions. It is also secreted by neutrophils in infection and inflammation sites. This glycoprotein possesses antimicrobial activity due to its capability to chelate two ferric ions per molecule, as well as to interact with bacterial and viral anionic surface components. The cationic features of Lf bind to cells, protecting the host from bacterial and viral injuries. Its anti-inflammatory activity is mediated by the ability to enter inside the nucleus of host cells, thus inhibiting the synthesis of proinflammatory cytokine genes. In particular, Lf down-regulates the synthesis of IL-6, which is involved in iron homeostasis disorders and leads to intracellular iron overload, favoring viral replication and infection. The well-known antiviral activity of Lf has been demonstrated against DNA, RNA, and enveloped and naked viruses and, therefore, Lf could be efficient in counteracting also SARS-CoV-2 infection. For this purpose, we performed in vitro assays, proving that Lf exerts an antiviral activity against SARS-COV-2 through direct attachment to both SARS-CoV-2 and cell surface components. This activity varied according to concentration (100/500 μg/ml), multiplicity of infection (0.1/0.01), and cell type (Vero E6/Caco-2 cells). Interestingly, the in silico results strongly supported the hypothesis of a direct recognition between Lf and the spike S glycoprotein, which can thus hinder viral entry into the cells. These in vitro observations led us to speculate a potential supplementary role of Lf in the management of COVID-19 patients.https://www.frontiersin.org/articles/10.3389/fphar.2021.666600/fulllactoferrinCOVID-19SARS-CoV-2spikebovine lactoferrin |