Pre-pandemic artificial MERS analog of polyfunctional SARS-CoV-2 S1/S2 furin cleavage site domain is unique among spike proteins of genus Betacoronavirus
Abstract Objectives SARS-CoV-2 spike (S) glycoprotein furin cleavage site is a key determinant of SARS-CoV-2 virulence and COVID-19 pathogencity. Located at the S1/S2 junction, it is unique among sarbecoviruses but frequently found among betacoronaviruses. Recent evidence suggests that this site inc...
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BMC
2024-12-01
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| Series: | BMC Genomic Data |
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| Online Access: | https://doi.org/10.1186/s12863-024-01290-2 |
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| author | Andreas Martin Lisewski |
| author_facet | Andreas Martin Lisewski |
| author_sort | Andreas Martin Lisewski |
| collection | DOAJ |
| description | Abstract Objectives SARS-CoV-2 spike (S) glycoprotein furin cleavage site is a key determinant of SARS-CoV-2 virulence and COVID-19 pathogencity. Located at the S1/S2 junction, it is unique among sarbecoviruses but frequently found among betacoronaviruses. Recent evidence suggests that this site includes two additional functional motifs: a pat7 nuclear localization signal and two flanking O-glycosites. However, a systematic genus and subgenus analysis of spike protein sequences bearing this polyfunctional sequence domain has been missing. Data description Here we report comprehensive sequence data to demonstrate that among spike proteins of genus Betacoronavirus and outside of the SARS-CoV-2 clade a fully analogous S1/S2 domain was found in only one other virus: the artificial MERS infectious clone MERS-MA30, described already in 2017, which was rationally selected from serial passage in genetically humanized mice. As the evolutionarily closest betacoronaviruses outside of the SARS-CoV-2 clade lack all its three functional motifs, these data extend—beyond natural evolution and zoonosis—the current view on SARS-CoV-2 pre-pandemic origins by presenting the analogous S1/S2 MERS-MA30 sequence domain as a precise molecular blueprint for SARS-CoV-2. |
| format | Article |
| id | doaj-art-940ffe1cb384484cb796e8ce40d6006c |
| institution | DOAJ |
| issn | 2730-6844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomic Data |
| spelling | doaj-art-940ffe1cb384484cb796e8ce40d6006c2025-08-20T02:40:18ZengBMCBMC Genomic Data2730-68442024-12-012511410.1186/s12863-024-01290-2Pre-pandemic artificial MERS analog of polyfunctional SARS-CoV-2 S1/S2 furin cleavage site domain is unique among spike proteins of genus BetacoronavirusAndreas Martin Lisewski0School of Science, Constructor UniversityAbstract Objectives SARS-CoV-2 spike (S) glycoprotein furin cleavage site is a key determinant of SARS-CoV-2 virulence and COVID-19 pathogencity. Located at the S1/S2 junction, it is unique among sarbecoviruses but frequently found among betacoronaviruses. Recent evidence suggests that this site includes two additional functional motifs: a pat7 nuclear localization signal and two flanking O-glycosites. However, a systematic genus and subgenus analysis of spike protein sequences bearing this polyfunctional sequence domain has been missing. Data description Here we report comprehensive sequence data to demonstrate that among spike proteins of genus Betacoronavirus and outside of the SARS-CoV-2 clade a fully analogous S1/S2 domain was found in only one other virus: the artificial MERS infectious clone MERS-MA30, described already in 2017, which was rationally selected from serial passage in genetically humanized mice. As the evolutionarily closest betacoronaviruses outside of the SARS-CoV-2 clade lack all its three functional motifs, these data extend—beyond natural evolution and zoonosis—the current view on SARS-CoV-2 pre-pandemic origins by presenting the analogous S1/S2 MERS-MA30 sequence domain as a precise molecular blueprint for SARS-CoV-2.https://doi.org/10.1186/s12863-024-01290-2GenomicsDirected evolutionArtificial virus hostBetacoronavirusFurin cleavage siteNuclear localization signal |
| spellingShingle | Andreas Martin Lisewski Pre-pandemic artificial MERS analog of polyfunctional SARS-CoV-2 S1/S2 furin cleavage site domain is unique among spike proteins of genus Betacoronavirus BMC Genomic Data Genomics Directed evolution Artificial virus host Betacoronavirus Furin cleavage site Nuclear localization signal |
| title | Pre-pandemic artificial MERS analog of polyfunctional SARS-CoV-2 S1/S2 furin cleavage site domain is unique among spike proteins of genus Betacoronavirus |
| title_full | Pre-pandemic artificial MERS analog of polyfunctional SARS-CoV-2 S1/S2 furin cleavage site domain is unique among spike proteins of genus Betacoronavirus |
| title_fullStr | Pre-pandemic artificial MERS analog of polyfunctional SARS-CoV-2 S1/S2 furin cleavage site domain is unique among spike proteins of genus Betacoronavirus |
| title_full_unstemmed | Pre-pandemic artificial MERS analog of polyfunctional SARS-CoV-2 S1/S2 furin cleavage site domain is unique among spike proteins of genus Betacoronavirus |
| title_short | Pre-pandemic artificial MERS analog of polyfunctional SARS-CoV-2 S1/S2 furin cleavage site domain is unique among spike proteins of genus Betacoronavirus |
| title_sort | pre pandemic artificial mers analog of polyfunctional sars cov 2 s1 s2 furin cleavage site domain is unique among spike proteins of genus betacoronavirus |
| topic | Genomics Directed evolution Artificial virus host Betacoronavirus Furin cleavage site Nuclear localization signal |
| url | https://doi.org/10.1186/s12863-024-01290-2 |
| work_keys_str_mv | AT andreasmartinlisewski prepandemicartificialmersanalogofpolyfunctionalsarscov2s1s2furincleavagesitedomainisuniqueamongspikeproteinsofgenusbetacoronavirus |