AUTHOR=Campione Elena , Lanna Caterina , Cosio Terenzio , Rosa Luigi , Conte Maria Pia , Iacovelli Federico , Romeo Alice , Falconi Mattia , Del Vecchio Claudia , Franchin Elisa , Lia Maria Stella , Minieri Marilena , Chiaramonte Carlo , Ciotti Marco , Nuccetelli Marzia , Terrinoni Alessandro , Iannuzzi Ilaria , Coppeda Luca , Magrini Andrea , Bernardini Sergio , Sabatini Stefano , Rosapepe Felice , Bartoletti Pier Luigi , Moricca Nicola , Di Lorenzo Andrea , Andreoni Massimo , Sarmati Loredana , Miani Alessandro , Piscitelli Prisco , Valenti Piera , Bianchi Luca TITLE=Lactoferrin Against SARS-CoV-2: In Vitro and In Silico Evidences JOURNAL=Frontiers in Pharmacology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.666600 DOI=10.3389/fphar.2021.666600 ISSN=1663-9812 ABSTRACT=

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.