MBL2 binds SARS-CoV-2 S

Stable Identifier
R-HSA-9957161
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
extracellular region
ReviewStatus
3/5
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MBL2 binds SARS-CoV-2 S
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Mannose-binding lectin (MBL2), a soluble pattern recognition receptor that recognizes and binds specific surface-bound carbohydrate motifs, such as mannose and fucose, in a Ca²⁺-dependent manner (Turner MW, 1996; Neth O et al., 2000), binds to the spike (S) protein of SARS-CoV-2 (Ali YM et al., 2021; Stravalaci M et al., 2022; Hurler L et al., 2023; Bayarri-Olmos R et al., 2024). The heavily glycosylated viral S contains several oligomannose-type N-glycans ( Watanabe Y et al., 2020; Wang D et al., 2023), which serve as potential binding sites of MBL2 (Stravalaci M et al., 2022; Bayarri-Olmos R et al., 2024). The viral S protein is incorporated into mature virions as a structural component within the S3:M:E:encapsidated SARS coronavirus genomic RNA:7a:O-glycosyl 3a tetramer complex (Yao H et al., 2020; Yan W et al., 2022). MBL2 binding can sterically hinder the interaction between the viral S protein and its receptor, angiotensin-converting enzyme 2 (ACE2), thereby limiting viral entry into host cells (Stravalaci M et al., 2022). Upon binding to the viral S protein, MBL2 activates the lectin pathway of the complement cascade by associating with MBL-associated serine proteases (MASP1 and MASP2), leading to opsonization, membrane attack complex (MAC) formation, and enhanced viral clearance (Ali YM et al., 2021; Stravalaci M et al., 2022). In addition, the nucleocapsid (N) protein of SARS-CoV-2 is thought to contribute to MBL-dependent, MASP2-mediated activation of the lectin pathway (Ali YM et al., 2021; Gao T et al., 2022). However, the precise mechanism of N protein involvement remains unclear, with studies reporting contradictory findings (Bally I et al., 2024; Kocsis A et al., 2024). Complement activation via MBL2 also contributes to the production of pro-inflammatory anaphylatoxins (C3a and C5a), which recruit immune cells and amplify cytokine production. Although complement activation supports viral clearance, excessive or uncontrolled activation may promote hyperinflammation and tissue injury, implicating the lectin pathway in COVID-19-related-immunopathologies (Rambaldi A et al., 2020; Medetalibeyoglu A et al., 2021; Stravalaci M et al., 2022; Hurler L et al., 2023; Bulla R et al., 2023; Takenaka H et al., 2023).
Literature References
PubMed ID Title Journal Year
39720734 Unraveling the impact of SARS-CoV-2 mutations on immunity: insights from innate immune recognition to antibody and T cell responses

Bayarri-Olmos, R, Sutta, A, Rosbjerg, A, Mortensen, MM, Helgstrand, C, Nielsen, PF, Pérez-Alós, L, González-García, B, Johnsen, LB, Matthiesen, F, Egebjerg, T, Hansen, CB, Sette, A, Grifoni, A, da Silva Antunes, R, Garred, P

Front Immunol 2024
35102342 Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules

Stravalaci, M, Pagani, I, Paraboschi, EM, Pedotti, M, Doni, A, Scavello, F, Mapelli, SN, Sironi, M, Perucchini, C, Varani, L, Matkovic, M, Cavalli, A, Cesana, D, Gallina, P, Pedemonte, N, Capurro, V, Clementi, N, Mancini, N, Invernizzi, P, Bayarri-Olmos, R, Garred, P, Rappuoli, R, Duga, S, Bottazzi, B, Uguccioni, M, Asselta, R, Vicenzi, E, Mantovani, A, Garlanda, C

Nat Immunol 2022
37051252 Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups

Hurler, L, Szilágyi, Á, Mescia, F, Bergamaschi, L, Mező, B, Sinkovits, G, Réti, M, Müller, V, Iványi, Z, Gál, J, Gopcsa, L, Reményi, P, Szathmáry, B, Lakatos, B, Szlávik, J, Bobek, I, Prohászka, ZZ, Förhécz, Z, Csuka, D, Kajdácsi, E, Cervenak, L, Kiszel, P, Masszi, T, Vályi-Nagy, I, Wurzner, R, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, -, Lyons, PA, Toonen, EJM, Prohászka, Z

Front Immunol 2023
34290717 Lectin Pathway Mediates Complement Activation by SARS-CoV-2 Proteins

Ali, YM, Ferrari, M, Lynch, NJ, Yaseen, S, Dudler, T, Gragerov, S, Demopulos, G, Heeney, JL, Schwaeble, WJ

Front Immunol 2021
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Authored
Shamovsky, V  (2025-06-17)
Created
Shamovsky, V  (2025-06-17)
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