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Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: in vivo, in silico and in vitro preliminary evidences

Elena Campione, Caterina Lanna, Terenzio Cosio, Luigi Rosa, Maria Pia Conte, Federico Iacovelli, Alice Romeo, Mattia Falconi, Claudia Del Vecchio, Elisa Franchin, Stella Lia, Marilena Miniero, Carlo Chiaramonte, Marco Ciotti, Marzia Nuccetelli, Alessandro Terrinoni, Ilaria Iannuzzi, Luca Coppeda, Andrea Magrini, Nicola Moricca, Stefano Sabatini, Felice Rosapepe, Pier Luigi Bartoletti, Sergio Bernardini, Massimo Andreoni, Piera Valenti, Luca Bianchi
doi: https://doi.org/10.1101/2020.08.11.244996
Elena Campione
1Dermatology Unit, University of Rome “Tor Vergata”, Rome, 00133, Italy
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  • For correspondence: elena.campione@uniroma2.it campioneelena@hotmail.com
Caterina Lanna
1Dermatology Unit, University of Rome “Tor Vergata”, Rome, 00133, Italy
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Terenzio Cosio
1Dermatology Unit, University of Rome “Tor Vergata”, Rome, 00133, Italy
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Luigi Rosa
2Department of Public Health and Infectious Diseases, University of Rome “La Sapienza”, 00185, Italy
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Maria Pia Conte
2Department of Public Health and Infectious Diseases, University of Rome “La Sapienza”, 00185, Italy
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Federico Iacovelli
3Department of Biology, Structural Bioinformatics Group, University of Rome “Tor Vergata”, Rome, 00133, Italy
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Alice Romeo
3Department of Biology, Structural Bioinformatics Group, University of Rome “Tor Vergata”, Rome, 00133, Italy
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Mattia Falconi
3Department of Biology, Structural Bioinformatics Group, University of Rome “Tor Vergata”, Rome, 00133, Italy
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Claudia Del Vecchio
4Department of Molecular Medicine, University of Padova, 35122 Padova, Italy
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Elisa Franchin
4Department of Molecular Medicine, University of Padova, 35122 Padova, Italy
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Stella Lia
5Department of Experimental Medicine, Tor Vergata University Hospital, Rome, 00133, Italy
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Marilena Miniero
5Department of Experimental Medicine, Tor Vergata University Hospital, Rome, 00133, Italy
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Carlo Chiaramonte
6Departement of statistics, University of Rome Tor Vergata, Rome, 00133, Italy
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Marco Ciotti
7Virology Unit, Tor Vergata University Hospital, Rome, 00133, Italy
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Marzia Nuccetelli
8Laboratory Medicine, Department of Experimental Medicine and Surgery, Tor Vergata University Hospital
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Alessandro Terrinoni
5Department of Experimental Medicine, Tor Vergata University Hospital, Rome, 00133, Italy
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Ilaria Iannuzzi
9Occupational Medicine Department, University of Rome “Tor Vergata”, Rome, 00133, Italy
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Luca Coppeda
9Occupational Medicine Department, University of Rome “Tor Vergata”, Rome, 00133, Italy
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Andrea Magrini
9Occupational Medicine Department, University of Rome “Tor Vergata”, Rome, 00133, Italy
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Nicola Moricca
10Villa dei Pini Hospital, Anzio (RM), Italy
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Stefano Sabatini
10Villa dei Pini Hospital, Anzio (RM), Italy
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Felice Rosapepe
11Pineta Grande Hospital, Caserta, Italy
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Pier Luigi Bartoletti
12Fimmg provincial, Rome, Italy
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Sergio Bernardini
8Laboratory Medicine, Department of Experimental Medicine and Surgery, Tor Vergata University Hospital
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Massimo Andreoni
13Infectious Disease Unit, Tor Vergata University Hospital, Rome, 00133, Italy
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Piera Valenti
2Department of Public Health and Infectious Diseases, University of Rome “La Sapienza”, 00185, Italy
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Luca Bianchi
1Dermatology Unit, University of Rome “Tor Vergata”, Rome, 00133, Italy
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SUMMARY

The current treatments against SARS-CoV-2 have proved so far inadequate. A potent antiviral drug is yet to be discovered. Lactoferrin, a multifunctional glycoprotein, secreted by exocrine glands and neutrophils, possesses an antiviral activity extendable to SARS-Cov-2.

We performed a randomized, prospective, interventional study assessing the role of oral and intra-nasal lactoferrin to treat mild-to-moderate and asymptomatic COVID-19 patients to prevent disease evolution. Lactoferrin induced an early viral clearance and a fast clinical symptoms recovery in addition to a statistically significant reduction of D-Dimer, Interleukin-6 and ferritin blood levels. The antiviral activity of lactoferrin related to its binding to SARS-CoV-2 and cells and protein-protein docking methods, provided the direct recognition between lactoferrin and spike S, thus hindering the spike S attachment to the human ACE2 receptor and consequently virus entering into the cells.

Lactoferrin can be used as a safe and efficacious natural agent to prevent and treat COVID-19 infection.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: in vivo, in silico and in vitro preliminary evidences
Elena Campione, Caterina Lanna, Terenzio Cosio, Luigi Rosa, Maria Pia Conte, Federico Iacovelli, Alice Romeo, Mattia Falconi, Claudia Del Vecchio, Elisa Franchin, Stella Lia, Marilena Miniero, Carlo Chiaramonte, Marco Ciotti, Marzia Nuccetelli, Alessandro Terrinoni, Ilaria Iannuzzi, Luca Coppeda, Andrea Magrini, Nicola Moricca, Stefano Sabatini, Felice Rosapepe, Pier Luigi Bartoletti, Sergio Bernardini, Massimo Andreoni, Piera Valenti, Luca Bianchi
bioRxiv 2020.08.11.244996; doi: https://doi.org/10.1101/2020.08.11.244996
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Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: in vivo, in silico and in vitro preliminary evidences
Elena Campione, Caterina Lanna, Terenzio Cosio, Luigi Rosa, Maria Pia Conte, Federico Iacovelli, Alice Romeo, Mattia Falconi, Claudia Del Vecchio, Elisa Franchin, Stella Lia, Marilena Miniero, Carlo Chiaramonte, Marco Ciotti, Marzia Nuccetelli, Alessandro Terrinoni, Ilaria Iannuzzi, Luca Coppeda, Andrea Magrini, Nicola Moricca, Stefano Sabatini, Felice Rosapepe, Pier Luigi Bartoletti, Sergio Bernardini, Massimo Andreoni, Piera Valenti, Luca Bianchi
bioRxiv 2020.08.11.244996; doi: https://doi.org/10.1101/2020.08.11.244996

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