Does SARS-CoV-2 bind to human ACE2 stronger than SARS-CoV?
The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, was declared a pandemic by the World Health Organization in March 2020. Genetically, SARS-CoV-2 is closely related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in mor...
| প্রধান লেখক: | , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
American Chemical Society
2020
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| _version_ | 1826264903621541888 |
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| author | Nguyen, HL Lan, PD Thai, NQ Nissley, DA O'Brien, EP Li, MS |
| author_facet | Nguyen, HL Lan, PD Thai, NQ Nissley, DA O'Brien, EP Li, MS |
| author_sort | Nguyen, HL |
| collection | OXFORD |
| description | The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, was declared a pandemic by the World Health Organization in March 2020. Genetically, SARS-CoV-2 is closely related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries from 2002 to 2003. Given the significant morbidity and mortality rate, the current pandemic poses a danger to all of humanity, prompting us to understand the activity of SARS-CoV-2 at the atomic level. Experimental studies have revealed that spike proteins of both SARS-CoV-2 and SARS-CoV bind to angiotensin-converting enzyme 2 (ACE2) before entering the cell for replication. However, the binding affinities reported by different groups seem to contradict each other. Wrapp et al. (Science2020, 367, 1260–1263) showed that the spike protein of SARS-CoV-2 binds to the ACE2 peptidase domain (ACE2-PD) more strongly than does SARS-CoV, and this fact may be associated with a greater severity of the new virus. However, Walls et al. (Cell2020, 181, 281–292) reported that SARS-CoV-2 exhibits a higher binding affinity, but the difference between the two variants is relatively small. To understand the binding mechanism and experimental results, we investigated how the receptor binding domain (RBD) of SARS-CoV (SARS-CoV-RBD) and SARS-CoV-2 (SARS-CoV-2-RBD) interacts with a human ACE2-PD using molecular modeling. We applied a coarse-grained model to calculate the dissociation constant and found that SARS-CoV-2 displays a 2-fold higher binding affinity. Using steered all-atom molecular dynamics simulations, we demonstrate that, like a coarse-grained simulation, SARS-CoV-2-RBD was associated with ACE2-PD more strongly than was SARS-CoV-RBD, as evidenced by a higher rupture force and larger pulling work. We show that the binding affinity of both viruses to ACE2 is driven by electrostatic interactions. |
| first_indexed | 2024-03-06T20:15:20Z |
| format | Journal article |
| id | oxford-uuid:2bf5c296-59ca-4589-88f5-875077391f1c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:15:20Z |
| publishDate | 2020 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:2bf5c296-59ca-4589-88f5-875077391f1c2022-03-26T12:34:07ZDoes SARS-CoV-2 bind to human ACE2 stronger than SARS-CoV?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2bf5c296-59ca-4589-88f5-875077391f1cEnglishSymplectic ElementsAmerican Chemical Society2020Nguyen, HLLan, PDThai, NQNissley, DAO'Brien, EPLi, MSThe 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, was declared a pandemic by the World Health Organization in March 2020. Genetically, SARS-CoV-2 is closely related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries from 2002 to 2003. Given the significant morbidity and mortality rate, the current pandemic poses a danger to all of humanity, prompting us to understand the activity of SARS-CoV-2 at the atomic level. Experimental studies have revealed that spike proteins of both SARS-CoV-2 and SARS-CoV bind to angiotensin-converting enzyme 2 (ACE2) before entering the cell for replication. However, the binding affinities reported by different groups seem to contradict each other. Wrapp et al. (Science2020, 367, 1260–1263) showed that the spike protein of SARS-CoV-2 binds to the ACE2 peptidase domain (ACE2-PD) more strongly than does SARS-CoV, and this fact may be associated with a greater severity of the new virus. However, Walls et al. (Cell2020, 181, 281–292) reported that SARS-CoV-2 exhibits a higher binding affinity, but the difference between the two variants is relatively small. To understand the binding mechanism and experimental results, we investigated how the receptor binding domain (RBD) of SARS-CoV (SARS-CoV-RBD) and SARS-CoV-2 (SARS-CoV-2-RBD) interacts with a human ACE2-PD using molecular modeling. We applied a coarse-grained model to calculate the dissociation constant and found that SARS-CoV-2 displays a 2-fold higher binding affinity. Using steered all-atom molecular dynamics simulations, we demonstrate that, like a coarse-grained simulation, SARS-CoV-2-RBD was associated with ACE2-PD more strongly than was SARS-CoV-RBD, as evidenced by a higher rupture force and larger pulling work. We show that the binding affinity of both viruses to ACE2 is driven by electrostatic interactions. |
| spellingShingle | Nguyen, HL Lan, PD Thai, NQ Nissley, DA O'Brien, EP Li, MS Does SARS-CoV-2 bind to human ACE2 stronger than SARS-CoV? |
| title | Does SARS-CoV-2 bind to human ACE2 stronger than SARS-CoV? |
| title_full | Does SARS-CoV-2 bind to human ACE2 stronger than SARS-CoV? |
| title_fullStr | Does SARS-CoV-2 bind to human ACE2 stronger than SARS-CoV? |
| title_full_unstemmed | Does SARS-CoV-2 bind to human ACE2 stronger than SARS-CoV? |
| title_short | Does SARS-CoV-2 bind to human ACE2 stronger than SARS-CoV? |
| title_sort | does sars cov 2 bind to human ace2 stronger than sars cov |
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