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Leçons biochimiques et statistiques de l’évolution du virus SARS-CoV-2 : nouveaux chemins pour combattre les virus

Authors :
Cluzel, Nicolas
Lambert, Amaury
Maday, Yvon
Turinici, Gabriel
Danchin, Antoine
Source :
Comptes Rendus Biologies, Vol 343, Iss 2, Pp 177-209 (2020)
Publication Year :
2020
Publisher :
Académie des sciences, 2020.

Abstract

In the fight against the spread of COVID-19 the emphasis is on vaccination or on reactivating existing drugs used for other purposes. The tight links that necessarily exist between the virus as it multiplies and the metabolism of its host are systematically ignored. Here we show that the metabolism of all cells is coordinated by the availability of a core building block of the cell’s genome, cytidine triphosphate (CTP). This metabolite is also the key to the synthesis of the viral envelope and to the translation of its genome into proteins. This unique role explains why evolution has led to the early emergence in animals of an antiviral immunity enzyme, viperin, that synthesizes a toxic analogue of CTP. The constraints arising from this dependency guide the evolution of the virus. With this in mind, we explored the real-time experiment taking place before our eyes using probabilistic modelling approaches to the molecular evolution of the virus. We have thus followed, almost on a daily basis, the evolution of the composition of the viral genome to link it to the progeny produced over time, particularly in the form of blooms that sparked a firework of viral mutations. Some of those certainly increase the propagation of the virus. This led us to make out the critical role in this evolution of several proteins of the virus, such as its nucleocapsid N, and more generally to begin to understand how the virus ties up the host metabolism to its own benefit. A way for the virus to escape CTP-dependent control in cells would be to infect cells that are not expected to grow, such as neurons. This may account for unexpected body sites of viral development in the present epidemic.

Details

Language :
English, French
ISSN :
17683238
Volume :
343
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Comptes Rendus Biologies
Publication Type :
Academic Journal
Accession number :
edsdoj.b6165bd1935404293ed634a7e0a9c15
Document Type :
article
Full Text :
https://doi.org/10.5802/crbiol.16