Article: Determination of intermediate state structures in the opening pathway of SARS-CoV-2 spike using cryo-electron microscopy.
2021 Volume 12, Issue 26, Page(s) 9168–9175
Abstract: ... cryo-electron microscopy approach to determine the opening pathway that brings spike from its inactive (closed ... conformation to its active (open) one. The knowledge of the structures of the intermediate states of spike ... Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19, a highly ...
| Abstract | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19, a highly infectious disease that is severely affecting our society and welfare systems. In order to develop therapeutic interventions against this condition, one promising strategy is to target spike, the trimeric transmembrane glycoprotein that the virus uses to recognise and bind its host cells. Here we use a metainference cryo-electron microscopy approach to determine the opening pathway that brings spike from its inactive (closed) conformation to its active (open) one. The knowledge of the structures of the intermediate states of spike along this opening pathway enables us to identify a cryptic pocket that is not exposed in the open and closed states. These results underline the opportunities offered by the determination of the structures of the transient intermediate states populated during the dynamics of proteins to allow the therapeutic targeting of otherwise invisible cryptic binding sites. |
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| Language | English |
| Publishing date | 2021-06-03 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 2559110-1 |
| ISSN | 2041-6539 ; 2041-6520 |
| ISSN (online) | 2041-6539 |
| ISSN | 2041-6520 |
| DOI | 10.1039/d1sc00244a |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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