A conserved motif within the NSP2 of SARS-CoV-2 is required for processing of the distal NSP1/NSP2 junction by NSP3
Abstract In 2019, the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) started to spread globally and caused the COVID-19 pandemic. SARS-CoV-2, like other members of the Coronaviridae, has a single-stranded, positive sense RNA genome about 30 kb in length, which is translated to ge...
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2025-07-01
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| author | Thea Kristensen Preben Normann Graham J. Belsham |
| author_facet | Thea Kristensen Preben Normann Graham J. Belsham |
| author_sort | Thea Kristensen |
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| description | Abstract In 2019, the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) started to spread globally and caused the COVID-19 pandemic. SARS-CoV-2, like other members of the Coronaviridae, has a single-stranded, positive sense RNA genome about 30 kb in length, which is translated to generate 16 non-structural proteins (NSPs); a set of sub-genomic mRNAs encode the structural and accessory proteins. The ORF1a precursor includes NSP1-11 and is processed by virus-encoded proteases to produce the mature proteins. We recently identified a short, highly conserved motif (YCPRP) within the structural protein precursor of foot-and-mouth disease virus (FMDV), a member of the Picornaviridae. This motif is conserved among picornaviruses and is found as (W/F/Y)-x-P-R-(P/A). The motif has a major influence on the processing of the FMDV capsid precursor (P1-2A) by the viral protease 3Cpro. We have now identified a similar motif (WVPRA) within the NSP2 of SARS-CoV-2. Interestingly, this motif is required for the efficient processing of the NSP1-NSP2 junction by the SARS-CoV-2 protease PLpro (NSP3) and a single amino acid substitution within the motif can abrogate cleavage of this junction. We hypothesise that this motif acts, within NSP1-NSP2, to enable this precursor to fold correctly and allow efficient processing of the NSP1/NSP2 junction. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-7d4d80d051fa44c8b7589f48ddc963a62025-08-20T04:02:46ZengNature PortfolioScientific Reports2045-23222025-07-011511910.1038/s41598-025-10244-2A conserved motif within the NSP2 of SARS-CoV-2 is required for processing of the distal NSP1/NSP2 junction by NSP3Thea Kristensen0Preben Normann1Graham J. Belsham2Department of Veterinary and Animal Sciences, University of CopenhagenDepartment of Veterinary and Animal Sciences, University of CopenhagenDepartment of Veterinary and Animal Sciences, University of CopenhagenAbstract In 2019, the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) started to spread globally and caused the COVID-19 pandemic. SARS-CoV-2, like other members of the Coronaviridae, has a single-stranded, positive sense RNA genome about 30 kb in length, which is translated to generate 16 non-structural proteins (NSPs); a set of sub-genomic mRNAs encode the structural and accessory proteins. The ORF1a precursor includes NSP1-11 and is processed by virus-encoded proteases to produce the mature proteins. We recently identified a short, highly conserved motif (YCPRP) within the structural protein precursor of foot-and-mouth disease virus (FMDV), a member of the Picornaviridae. This motif is conserved among picornaviruses and is found as (W/F/Y)-x-P-R-(P/A). The motif has a major influence on the processing of the FMDV capsid precursor (P1-2A) by the viral protease 3Cpro. We have now identified a similar motif (WVPRA) within the NSP2 of SARS-CoV-2. Interestingly, this motif is required for the efficient processing of the NSP1-NSP2 junction by the SARS-CoV-2 protease PLpro (NSP3) and a single amino acid substitution within the motif can abrogate cleavage of this junction. We hypothesise that this motif acts, within NSP1-NSP2, to enable this precursor to fold correctly and allow efficient processing of the NSP1/NSP2 junction.https://doi.org/10.1038/s41598-025-10244-2SARS-CoV-2Intramolecular chaperoneCoronavirusNSP2Proteolytic processing |
| spellingShingle | Thea Kristensen Preben Normann Graham J. Belsham A conserved motif within the NSP2 of SARS-CoV-2 is required for processing of the distal NSP1/NSP2 junction by NSP3 Scientific Reports SARS-CoV-2 Intramolecular chaperone Coronavirus NSP2 Proteolytic processing |
| title | A conserved motif within the NSP2 of SARS-CoV-2 is required for processing of the distal NSP1/NSP2 junction by NSP3 |
| title_full | A conserved motif within the NSP2 of SARS-CoV-2 is required for processing of the distal NSP1/NSP2 junction by NSP3 |
| title_fullStr | A conserved motif within the NSP2 of SARS-CoV-2 is required for processing of the distal NSP1/NSP2 junction by NSP3 |
| title_full_unstemmed | A conserved motif within the NSP2 of SARS-CoV-2 is required for processing of the distal NSP1/NSP2 junction by NSP3 |
| title_short | A conserved motif within the NSP2 of SARS-CoV-2 is required for processing of the distal NSP1/NSP2 junction by NSP3 |
| title_sort | conserved motif within the nsp2 of sars cov 2 is required for processing of the distal nsp1 nsp2 junction by nsp3 |
| topic | SARS-CoV-2 Intramolecular chaperone Coronavirus NSP2 Proteolytic processing |
| url | https://doi.org/10.1038/s41598-025-10244-2 |
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