MANNOSE-BINDING LECTIN (MBL) INHIBITS SARS-CoV-2 INFECTION and REPLICATION in VITRO
Topics in Antiviral Medicine
; 30(1 SUPPL):63-64, 2022.
Article
in English
| EMBASE | ID: covidwho-1880680
ABSTRACT
Background:
Humoral innate immunity consists of a limited, but diverse, set of humoral fluid phase pattern recognition molecules (PRMs) that represent a first line of resistance against microbial invaders by promoting pathogen disposal by phagocytosis, complement activation and inflammation. These factors encompass complement, ficolin, collectin and pentraxin family of proteins.Methods:
We have analyzed the activity of PRMs for their potential capacity of inhibiting SARS-CoV-2 entry and replication into epithelial cells by a microneutralization assay based on a lentiviral particles pseudotyped with the SARS-CoV-2 spike protein in HEK293T cells overexpressing the angiotensin converting enzyme 2 (ACE2). Either SARS-CoV-2 or target cells were incubated with Mannose Binding Lectin (MBL, concentration range 1-50 μ g/ml) to further characterize its anti-viral activity for 1 h prior to infection in both human Calu-3 cells and air-liquid interface cultures of human bronchial epithelial cells (HBEC). Binding experiments were carried out with SARS-CoV-2 Spike protein and recombinant MBL to further investigate its antiviral action.Results:
Among 12 PRMs tested, only MBL inhibited viral entry in the pseudotyped neutralization assay. Furthermore, MBL protein inhibited SARS-CoV-2 viral replication in Calu-3 and HBEC by ca. one log10 at the top concentration (10 μ g/ml and 50 μ g/ml, respectively). MBL antiviral activity was confirmed also against alpha, beta and gamma SARS-CoV-2 variants of concern. Binding experiments showed that MBL specifically interacts with the trimeric form of SARS-CoV-2 spike.Conclusion:
MBL binds to the Spike protein in its active trimeric conformation leading to the inhibition of SARS-CoV-2 infection and replication in vitro. These results suggest that MBL possesses an antiviral activity against SARS-CoV-2 that could bear therapeutic potential.
angiotensin converting enzyme 2; endogenous compound; mannose binding lectin; virus spike protein; antiviral activity; bronchiole cell; Calu-3 cell line; cell culture; concentration (parameter); conference abstract; controlled study; coronavirus disease 2019; enzyme activity; gene overexpression; HBEC cell line (bronchial epithelium); HEK293T cell line; human; human cell; in vitro study; nonhuman; pattern recognition; protein conformation; protein expression; Severe acute respiratory syndrome coronavirus 2; spike; target cell; trimerization; variant of concern; virus entry; virus replication
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Topics in Antiviral Medicine
Year:
2022
Document Type:
Article
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