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

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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.

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

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Article information


Submitted
13 Jan 2021
Accepted
01 Jun 2021
First published
03 Jun 2021

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2021, Advance Article
Article type
Edge Article

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

Z. F. Brotzakis, T. Löhr and M. Vendruscolo, Chem. Sci., 2021, Advance Article , DOI: 10.1039/D1SC00244A

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