A Vaccine Strategy Based on the Identification of an Annular Ganglioside Binding Motif in Monkeypox Virus Protein E8L
The recent outbreak of Monkeypox virus requires the development of a vaccine specifically directed against this virus as quickly as possible. We propose here a new strategy based on a two-step analysis combining (i) the search for binding domains of viral proteins to gangliosides present in lipid ra...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/11/2531 |
| _version_ | 1827643605399896064 |
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| author | Jacques Fantini Henri Chahinian Nouara Yahi |
| author_facet | Jacques Fantini Henri Chahinian Nouara Yahi |
| author_sort | Jacques Fantini |
| collection | DOAJ |
| description | The recent outbreak of Monkeypox virus requires the development of a vaccine specifically directed against this virus as quickly as possible. We propose here a new strategy based on a two-step analysis combining (i) the search for binding domains of viral proteins to gangliosides present in lipid rafts of host cells, and (ii) B epitope predictions. Based on previous studies of HIV and SARS-CoV-2 proteins, we show that the Monkeypox virus cell surface-binding protein E8L possesses a ganglioside-binding motif consisting of several subsites forming a ring structure. The binding of the E8L protein to a cluster of gangliosides GM1 mimicking a lipid raft domain is driven by both shape and electrostatic surface potential complementarities. An induced-fit mechanism unmasks selected amino acid side chains of the motif without significantly affecting the secondary structure of the protein. The ganglioside-binding motif overlaps three potential linear B epitopes that are well exposed on the unbound E8L surface that faces the host cell membrane. This situation is ideal for generating neutralizing antibodies. We thus suggest using these three sequences derived from the E8L protein as immunogens in a vaccine formulation (recombinant protein, synthetic peptides or genetically based) specific for Monkeypox virus. This lipid raft/ganglioside-based strategy could be used for developing therapeutic and vaccine responses to future virus outbreaks, in parallel to existing solutions. |
| first_indexed | 2024-03-09T17:56:37Z |
| format | Article |
| id | doaj.art-d7f3605959b5416e87782dc66e60c891 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T17:56:37Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-d7f3605959b5416e87782dc66e60c8912023-11-24T10:18:43ZengMDPI AGViruses1999-49152022-11-011411253110.3390/v14112531A Vaccine Strategy Based on the Identification of an Annular Ganglioside Binding Motif in Monkeypox Virus Protein E8LJacques Fantini0Henri Chahinian1Nouara Yahi2INSERM UMR_S-1072 and Faculty of Medicine, Aix-Marseille Université, Boulevard Pierre Dramard, 13015 Marseille, FranceINSERM UMR_S-1072 and Faculty of Medicine, Aix-Marseille Université, Boulevard Pierre Dramard, 13015 Marseille, FranceINSERM UMR_S-1072 and Faculty of Medicine, Aix-Marseille Université, Boulevard Pierre Dramard, 13015 Marseille, FranceThe recent outbreak of Monkeypox virus requires the development of a vaccine specifically directed against this virus as quickly as possible. We propose here a new strategy based on a two-step analysis combining (i) the search for binding domains of viral proteins to gangliosides present in lipid rafts of host cells, and (ii) B epitope predictions. Based on previous studies of HIV and SARS-CoV-2 proteins, we show that the Monkeypox virus cell surface-binding protein E8L possesses a ganglioside-binding motif consisting of several subsites forming a ring structure. The binding of the E8L protein to a cluster of gangliosides GM1 mimicking a lipid raft domain is driven by both shape and electrostatic surface potential complementarities. An induced-fit mechanism unmasks selected amino acid side chains of the motif without significantly affecting the secondary structure of the protein. The ganglioside-binding motif overlaps three potential linear B epitopes that are well exposed on the unbound E8L surface that faces the host cell membrane. This situation is ideal for generating neutralizing antibodies. We thus suggest using these three sequences derived from the E8L protein as immunogens in a vaccine formulation (recombinant protein, synthetic peptides or genetically based) specific for Monkeypox virus. This lipid raft/ganglioside-based strategy could be used for developing therapeutic and vaccine responses to future virus outbreaks, in parallel to existing solutions.https://www.mdpi.com/1999-4915/14/11/2531pox virusMonkeypox virusvaccinegangliosidelipid raft |
| spellingShingle | Jacques Fantini Henri Chahinian Nouara Yahi A Vaccine Strategy Based on the Identification of an Annular Ganglioside Binding Motif in Monkeypox Virus Protein E8L Viruses pox virus Monkeypox virus vaccine ganglioside lipid raft |
| title | A Vaccine Strategy Based on the Identification of an Annular Ganglioside Binding Motif in Monkeypox Virus Protein E8L |
| title_full | A Vaccine Strategy Based on the Identification of an Annular Ganglioside Binding Motif in Monkeypox Virus Protein E8L |
| title_fullStr | A Vaccine Strategy Based on the Identification of an Annular Ganglioside Binding Motif in Monkeypox Virus Protein E8L |
| title_full_unstemmed | A Vaccine Strategy Based on the Identification of an Annular Ganglioside Binding Motif in Monkeypox Virus Protein E8L |
| title_short | A Vaccine Strategy Based on the Identification of an Annular Ganglioside Binding Motif in Monkeypox Virus Protein E8L |
| title_sort | vaccine strategy based on the identification of an annular ganglioside binding motif in monkeypox virus protein e8l |
| topic | pox virus Monkeypox virus vaccine ganglioside lipid raft |
| url | https://www.mdpi.com/1999-4915/14/11/2531 |
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