Determination of intermediate state structures in the opening pathway of SARS-CoV-2 spike using cryo-electron microscopy.


Type
Article
Change log
Authors
Brotzakis, Z Faidon 
Löhr, Thomas 
Vendruscolo, Michele  ORCID logo  https://orcid.org/0000-0002-3616-1610
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.

Description
Keywords
34 Chemical Sciences, Lung, Prevention, Emerging Infectious Diseases, Pneumonia, Infectious Diseases, Pneumonia & Influenza, Vaccine Related, Biodefense, 3 Good Health and Well Being
Journal Title
Chem Sci
Conference Name
Journal ISSN
2041-6520
2041-6539
Volume Title
12
Publisher
Royal Society of Chemistry (RSC)