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Spike-mediated viral membrane fusion is inhibited by a specific anti-IFITM2 monoclonal antibody.
Antiviral Res. 2023 03; 211:105546.AR

Abstract

The early steps of viral infection involve protein complexes and structural lipid rearrangements which characterize the peculiar strategies of each virus to invade permissive host cells. Members of the human immune-related interferon-induced transmembrane (IFITM) protein family have been described as inhibitors of the entry of a broad range of viruses into the host cells. Recently, it has been shown that SARS-CoV-2 is able to hijack IFITM2 for efficient infection. Here, we report the characterization of a newly generated specific anti-IFITM2 mAb able to impair Spike-mediated internalization of SARS-CoV-2 in host cells and, consequently, to reduce the SARS-CoV-2 cytopathic effects and syncytia formation. Furthermore, the anti-IFITM2 mAb reduced HSVs- and RSV-dependent cytopathic effects, suggesting that the IFITM2-mediated mechanism of host cell invasion might be shared with other viruses besides SARS-CoV-2. These results show the specific role of IFITM2 in mediating viral entry into the host cell and its candidacy as a cell target for antiviral therapeutic strategies.

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Authors+Show Affiliations

Basile A
Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy.
Zannella C
Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, 80138, Italy.
De Marco M
Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy; FIBROSYS s.r.l., University of Salerno, Baronissi, SA, 84081, Italy.
Sanna G
Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, 09042, Italy.
Franci G
Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy.
Galdiero M
Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, 80138, Italy.
Manzin A
Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, 09042, Italy.
De Laurenzi V
FIBROSYS s.r.l., University of Salerno, Baronissi, SA, 84081, Italy; Department of Innovative Technologies in Medicine and Dentistry, University of Chieti-Pescara, Chieti, Italy.
Chetta M
U.O.C. Medical and Laboratory Genetics, A.O.R.N, Cardarelli, Naples, 80131, Italy.
Rosati A
Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy; FIBROSYS s.r.l., University of Salerno, Baronissi, SA, 84081, Italy. Electronic address: arosati@unisa.it.
Turco MC
Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy; FIBROSYS s.r.l., University of Salerno, Baronissi, SA, 84081, Italy.
Marzullo L
Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Baronissi, SA, 84081, Italy; FIBROSYS s.r.l., University of Salerno, Baronissi, SA, 84081, Italy.

MeSH

HumansVirus InternalizationSARS-CoV-2Antigens, DifferentiationCOVID-19Antibodies, MonoclonalSpike Glycoprotein, CoronavirusMembrane FusionMembrane Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

36669656

Citation

Basile, Anna, et al. "Spike-mediated Viral Membrane Fusion Is Inhibited By a Specific anti-IFITM2 Monoclonal Antibody." Antiviral Research, vol. 211, 2023, p. 105546.
Basile A, Zannella C, De Marco M, et al. Spike-mediated viral membrane fusion is inhibited by a specific anti-IFITM2 monoclonal antibody. Antiviral Res. 2023;211:105546.
Basile, A., Zannella, C., De Marco, M., Sanna, G., Franci, G., Galdiero, M., Manzin, A., De Laurenzi, V., Chetta, M., Rosati, A., Turco, M. C., & Marzullo, L. (2023). Spike-mediated viral membrane fusion is inhibited by a specific anti-IFITM2 monoclonal antibody. Antiviral Research, 211, 105546. https://doi.org/10.1016/j.antiviral.2023.105546
Basile A, et al. Spike-mediated Viral Membrane Fusion Is Inhibited By a Specific anti-IFITM2 Monoclonal Antibody. Antiviral Res. 2023;211:105546. PubMed PMID: 36669656.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spike-mediated viral membrane fusion is inhibited by a specific anti-IFITM2 monoclonal antibody. AU - Basile,Anna, AU - Zannella,Carla, AU - De Marco,Margot, AU - Sanna,Giuseppina, AU - Franci,Gianluigi, AU - Galdiero,Massimiliano, AU - Manzin,Aldo, AU - De Laurenzi,Vincenzo, AU - Chetta,Massimiliano, AU - Rosati,Alessandra, AU - Turco,Maria Caterina, AU - Marzullo,Liberato, Y1 - 2023/01/18/ PY - 2022/10/13/received PY - 2023/01/12/revised PY - 2023/01/15/accepted PY - 2023/1/21/pubmed PY - 2023/3/3/medline PY - 2023/1/20/entrez KW - IFITM2 KW - Monoclonal antibody KW - SARS-CoV-2 KW - Syncytia KW - Virus entry SP - 105546 EP - 105546 JF - Antiviral research JO - Antiviral Res VL - 211 N2 - The early steps of viral infection involve protein complexes and structural lipid rearrangements which characterize the peculiar strategies of each virus to invade permissive host cells. Members of the human immune-related interferon-induced transmembrane (IFITM) protein family have been described as inhibitors of the entry of a broad range of viruses into the host cells. Recently, it has been shown that SARS-CoV-2 is able to hijack IFITM2 for efficient infection. Here, we report the characterization of a newly generated specific anti-IFITM2 mAb able to impair Spike-mediated internalization of SARS-CoV-2 in host cells and, consequently, to reduce the SARS-CoV-2 cytopathic effects and syncytia formation. Furthermore, the anti-IFITM2 mAb reduced HSVs- and RSV-dependent cytopathic effects, suggesting that the IFITM2-mediated mechanism of host cell invasion might be shared with other viruses besides SARS-CoV-2. These results show the specific role of IFITM2 in mediating viral entry into the host cell and its candidacy as a cell target for antiviral therapeutic strategies. SN - 1872-9096 UR - https://www.unboundmedicine.com/medline/citation/36669656/Spike_mediated_viral_membrane_fusion_is_inhibited_by_a_specific_anti_IFITM2_monoclonal_antibody_ DB - PRIME DP - Unbound Medicine ER -