Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an immediate, major threat to public health across the globe. Here we report an in-depth molecular analysis to reconstruct the evolutionary origins of the enhanced pathogenicity of SARS-CoV-2 and other coronaviruses that are severe h...
| Main Authors: | , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Published: |
Proceedings of the National Academy of Sciences
2020
|
| Online Access: | https://hdl.handle.net/1721.1/125772 |
| _version_ | 1826199366718717952 |
|---|---|
| author | Gussow, Ayal B. Auslander, Noam Faure, Guilhem Wolf, Yuri I. Zhang, Feng Koonin, Eugene V. |
| author2 | McGovern Institute for Brain Research at MIT |
| author_facet | McGovern Institute for Brain Research at MIT Gussow, Ayal B. Auslander, Noam Faure, Guilhem Wolf, Yuri I. Zhang, Feng Koonin, Eugene V. |
| author_sort | Gussow, Ayal B. |
| collection | MIT |
| description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an immediate, major threat to public health across the globe. Here we report an in-depth molecular analysis to reconstruct the evolutionary origins of the enhanced pathogenicity of SARS-CoV-2 and other coronaviruses that are severe human pathogens. Using integrated comparative genomics and machine learning techniques, we identify key genomic features that differentiate SARS-CoV-2 and the viruses behind the two previous deadly coronavirus outbreaks, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), from less pathogenic coronaviruses. These features include enhancement of the nuclear localization signals in the nucleocapsid protein and distinct inserts in the spike glycoprotein that appear to be associated with high case fatality rate of these coronaviruses as well as the host switch from animals to humans. The identified features could be crucial contributors to coronavirus pathogenicity and possible targets for diagnostics, prognostication, and interventions. |
| first_indexed | 2024-09-23T11:19:04Z |
| format | Article |
| id | mit-1721.1/125772 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:19:04Z |
| publishDate | 2020 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1257722022-10-01T02:46:35Z Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses Gussow, Ayal B. Auslander, Noam Faure, Guilhem Wolf, Yuri I. Zhang, Feng Koonin, Eugene V. McGovern Institute for Brain Research at MIT Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Massachusetts Institute of Technology. Department of Biological Engineering Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an immediate, major threat to public health across the globe. Here we report an in-depth molecular analysis to reconstruct the evolutionary origins of the enhanced pathogenicity of SARS-CoV-2 and other coronaviruses that are severe human pathogens. Using integrated comparative genomics and machine learning techniques, we identify key genomic features that differentiate SARS-CoV-2 and the viruses behind the two previous deadly coronavirus outbreaks, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), from less pathogenic coronaviruses. These features include enhancement of the nuclear localization signals in the nucleocapsid protein and distinct inserts in the spike glycoprotein that appear to be associated with high case fatality rate of these coronaviruses as well as the host switch from animals to humans. The identified features could be crucial contributors to coronavirus pathogenicity and possible targets for diagnostics, prognostication, and interventions. National Institutes of Health (Grant 1R01- MH110049) National Institutes of Health (Grant 1DP1-HL141201) 2020-06-11T20:48:15Z 2020-06-11T20:48:15Z 2020-06 2020-04 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 https://hdl.handle.net/1721.1/125772 Gussow, Ayal B. et al. "Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses." Proceedings of the National Academy of Sciences (June 2020) © 2020 the Author(s) http://dx.doi.org/10.1073/pnas.2008176117 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Gussow, Ayal B. Auslander, Noam Faure, Guilhem Wolf, Yuri I. Zhang, Feng Koonin, Eugene V. Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses |
| title | Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses |
| title_full | Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses |
| title_fullStr | Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses |
| title_full_unstemmed | Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses |
| title_short | Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses |
| title_sort | genomic determinants of pathogenicity in sars cov 2 and other human coronaviruses |
| url | https://hdl.handle.net/1721.1/125772 |
| work_keys_str_mv | AT gussowayalb genomicdeterminantsofpathogenicityinsarscov2andotherhumancoronaviruses AT auslandernoam genomicdeterminantsofpathogenicityinsarscov2andotherhumancoronaviruses AT faureguilhem genomicdeterminantsofpathogenicityinsarscov2andotherhumancoronaviruses AT wolfyurii genomicdeterminantsofpathogenicityinsarscov2andotherhumancoronaviruses AT zhangfeng genomicdeterminantsofpathogenicityinsarscov2andotherhumancoronaviruses AT koonineugenev genomicdeterminantsofpathogenicityinsarscov2andotherhumancoronaviruses |