Targeting the YXXΦ Motifs of the SARS Coronaviruses 1 and 2 ORF3a Peptides by In Silico Analysis to Predict Novel Virus—Host Interactions
The emerging SARS-CoV and SARS-CoV-2 belong to the family of “common cold” RNA coronaviruses, and they are responsible for the 2003 epidemic and the current pandemic with over 6.3 M deaths worldwide. The ORF3a gene is conserved in both viruses and codes for the accessory protein ORF3a, with unclear...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/8/1052 |
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| author | Athanassios Kakkanas Eirini Karamichali Efthymia Ioanna Koufogeorgou Stathis D. Kotsakis Urania Georgopoulou Pelagia Foka |
| author_facet | Athanassios Kakkanas Eirini Karamichali Efthymia Ioanna Koufogeorgou Stathis D. Kotsakis Urania Georgopoulou Pelagia Foka |
| author_sort | Athanassios Kakkanas |
| collection | DOAJ |
| description | The emerging SARS-CoV and SARS-CoV-2 belong to the family of “common cold” RNA coronaviruses, and they are responsible for the 2003 epidemic and the current pandemic with over 6.3 M deaths worldwide. The ORF3a gene is conserved in both viruses and codes for the accessory protein ORF3a, with unclear functions, possibly related to viral virulence and pathogenesis. The tyrosine-based YXXΦ motif (Φ: bulky hydrophobic residue—L/I/M/V/F) was originally discovered to mediate clathrin-dependent endocytosis of membrane-spanning proteins. Many viruses employ the YXXΦ motif to achieve efficient receptor-guided internalisation in host cells, maintain the structural integrity of their capsids and enhance viral replication. Importantly, this motif has been recently identified on the ORF3a proteins of SARS-CoV and SARS-CoV-2. Given that the ORF3a aa sequence is not fully conserved between the two SARS viruses, we aimed to map in silico structural differences and putative sequence-driven alterations of regulatory elements within and adjacently to the YXXΦ motifs that could predict variations in ORF3a functions. Using robust bioinformatics tools, we investigated the presence of relevant post-translational modifications and the YXXΦ motif involvement in protein-protein interactions. Our study suggests that the predicted YXXΦ-related features may confer specific—yet to be discovered—functions to ORF3a proteins, significant to the new virus and related to enhanced propagation, host immune regulation and virulence. |
| first_indexed | 2024-03-09T04:39:41Z |
| format | Article |
| id | doaj.art-149145c174a74cfa944a76d868bd3921 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T04:39:41Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-149145c174a74cfa944a76d868bd39212023-12-03T13:22:32ZengMDPI AGBiomolecules2218-273X2022-07-01128105210.3390/biom12081052Targeting the YXXΦ Motifs of the SARS Coronaviruses 1 and 2 ORF3a Peptides by In Silico Analysis to Predict Novel Virus—Host InteractionsAthanassios Kakkanas0Eirini Karamichali1Efthymia Ioanna Koufogeorgou2Stathis D. Kotsakis3Urania Georgopoulou4Pelagia Foka5Laboratory of Molecular Virology, Hellenic Pasteur Institute, 115-21 Athens, GreeceLaboratory of Molecular Virology, Hellenic Pasteur Institute, 115-21 Athens, GreeceLaboratory of Molecular Virology, Hellenic Pasteur Institute, 115-21 Athens, GreeceLaboratory of Bacteriology, Hellenic Pasteur Institute, 115-21 Athens, GreeceLaboratory of Molecular Virology, Hellenic Pasteur Institute, 115-21 Athens, GreeceLaboratory of Molecular Virology, Hellenic Pasteur Institute, 115-21 Athens, GreeceThe emerging SARS-CoV and SARS-CoV-2 belong to the family of “common cold” RNA coronaviruses, and they are responsible for the 2003 epidemic and the current pandemic with over 6.3 M deaths worldwide. The ORF3a gene is conserved in both viruses and codes for the accessory protein ORF3a, with unclear functions, possibly related to viral virulence and pathogenesis. The tyrosine-based YXXΦ motif (Φ: bulky hydrophobic residue—L/I/M/V/F) was originally discovered to mediate clathrin-dependent endocytosis of membrane-spanning proteins. Many viruses employ the YXXΦ motif to achieve efficient receptor-guided internalisation in host cells, maintain the structural integrity of their capsids and enhance viral replication. Importantly, this motif has been recently identified on the ORF3a proteins of SARS-CoV and SARS-CoV-2. Given that the ORF3a aa sequence is not fully conserved between the two SARS viruses, we aimed to map in silico structural differences and putative sequence-driven alterations of regulatory elements within and adjacently to the YXXΦ motifs that could predict variations in ORF3a functions. Using robust bioinformatics tools, we investigated the presence of relevant post-translational modifications and the YXXΦ motif involvement in protein-protein interactions. Our study suggests that the predicted YXXΦ-related features may confer specific—yet to be discovered—functions to ORF3a proteins, significant to the new virus and related to enhanced propagation, host immune regulation and virulence.https://www.mdpi.com/2218-273X/12/8/1052SARS-CoVSARS-CoV-2ORF3aYXXΦ motifpost-translational modificationsimmune response |
| spellingShingle | Athanassios Kakkanas Eirini Karamichali Efthymia Ioanna Koufogeorgou Stathis D. Kotsakis Urania Georgopoulou Pelagia Foka Targeting the YXXΦ Motifs of the SARS Coronaviruses 1 and 2 ORF3a Peptides by In Silico Analysis to Predict Novel Virus—Host Interactions Biomolecules SARS-CoV SARS-CoV-2 ORF3a YXXΦ motif post-translational modifications immune response |
| title | Targeting the YXXΦ Motifs of the SARS Coronaviruses 1 and 2 ORF3a Peptides by In Silico Analysis to Predict Novel Virus—Host Interactions |
| title_full | Targeting the YXXΦ Motifs of the SARS Coronaviruses 1 and 2 ORF3a Peptides by In Silico Analysis to Predict Novel Virus—Host Interactions |
| title_fullStr | Targeting the YXXΦ Motifs of the SARS Coronaviruses 1 and 2 ORF3a Peptides by In Silico Analysis to Predict Novel Virus—Host Interactions |
| title_full_unstemmed | Targeting the YXXΦ Motifs of the SARS Coronaviruses 1 and 2 ORF3a Peptides by In Silico Analysis to Predict Novel Virus—Host Interactions |
| title_short | Targeting the YXXΦ Motifs of the SARS Coronaviruses 1 and 2 ORF3a Peptides by In Silico Analysis to Predict Novel Virus—Host Interactions |
| title_sort | targeting the yxxφ motifs of the sars coronaviruses 1 and 2 orf3a peptides by in silico analysis to predict novel virus host interactions |
| topic | SARS-CoV SARS-CoV-2 ORF3a YXXΦ motif post-translational modifications immune response |
| url | https://www.mdpi.com/2218-273X/12/8/1052 |
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