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Article: A Path toward SARS-CoV-2 Attenuation: Metabolic Pressure on CTP Synthesis Rules the Virus Evolution

TitleA Path toward SARS-CoV-2 Attenuation: Metabolic Pressure on CTP Synthesis Rules the Virus Evolution
Authors
KeywordsABCE1
cytoophidia
Maxwell's demon
Nsp1
phosphoribosyltransferase
Issue Date2020
PublisherOxford University Press for Society for Molecular Biology and Evolution. The Journal's web site is located at http://gbe.oxfordjournals.org
Citation
Genome Biology and Evolution, 2020, v. 12, p. 2467-2485 How to Cite?
AbstractIn the context of the COVID-19 pandemic, we describe here the singular metabolic background that constrains enveloped RNA viruses to evolve toward likely attenuation in the long term, possibly after a step of increased pathogenicity. Cytidine triphosphate (CTP) is at the crossroad of the processes allowing SARS-CoV-2 to multiply, because CTP is in demand for four essential metabolic steps. It is a building block of the virus genome, it is required for synthesis of the cytosine-based liponucleotide precursors of the viral envelope, it is a critical building block of the host transfer RNAs synthesis and it is required for synthesis of dolichol-phosphate, a precursor of viral protein glycosylation. The CCA 3'-end of all the transfer RNAs required to translate the RNA genome and further transcripts into the proteins used to build active virus copies is not coded in the human genome. It must be synthesized de novo from CTP and ATP. Furthermore, intermediary metabolism is built on compulsory steps of synthesis and salvage of cytosine-based metabolites via uridine triphosphate that keep limiting CTP availability. As a consequence, accidental replication errors tend to replace cytosine by uracil in the genome, unless recombination events allow the sequence to return to its ancestral sequences. We document some of the consequences of this situation in the function of viral proteins. This unique metabolic setup allowed us to highlight and provide a raison d'etre to viperin, an enzyme of innate antiviral immunity, which synthesizes 3'-deoxy-3',4'-didehydro-CTP as an extremely efficient antiviral nucleotide.
Persistent Identifierhttp://hdl.handle.net/10722/295769
ISSN
2023 Impact Factor: 3.2
2023 SCImago Journal Rankings: 1.315
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorOu, Z-
dc.contributor.authorOuzounis, C-
dc.contributor.authorWang, D-
dc.contributor.authorSun, W-
dc.contributor.authorLi, J-
dc.contributor.authorChen, W-
dc.contributor.authorMarlière, P-
dc.contributor.authorDanchin, A-
dc.date.accessioned2021-02-08T08:13:45Z-
dc.date.available2021-02-08T08:13:45Z-
dc.date.issued2020-
dc.identifier.citationGenome Biology and Evolution, 2020, v. 12, p. 2467-2485-
dc.identifier.issn1759-6653-
dc.identifier.urihttp://hdl.handle.net/10722/295769-
dc.description.abstractIn the context of the COVID-19 pandemic, we describe here the singular metabolic background that constrains enveloped RNA viruses to evolve toward likely attenuation in the long term, possibly after a step of increased pathogenicity. Cytidine triphosphate (CTP) is at the crossroad of the processes allowing SARS-CoV-2 to multiply, because CTP is in demand for four essential metabolic steps. It is a building block of the virus genome, it is required for synthesis of the cytosine-based liponucleotide precursors of the viral envelope, it is a critical building block of the host transfer RNAs synthesis and it is required for synthesis of dolichol-phosphate, a precursor of viral protein glycosylation. The CCA 3'-end of all the transfer RNAs required to translate the RNA genome and further transcripts into the proteins used to build active virus copies is not coded in the human genome. It must be synthesized de novo from CTP and ATP. Furthermore, intermediary metabolism is built on compulsory steps of synthesis and salvage of cytosine-based metabolites via uridine triphosphate that keep limiting CTP availability. As a consequence, accidental replication errors tend to replace cytosine by uracil in the genome, unless recombination events allow the sequence to return to its ancestral sequences. We document some of the consequences of this situation in the function of viral proteins. This unique metabolic setup allowed us to highlight and provide a raison d'etre to viperin, an enzyme of innate antiviral immunity, which synthesizes 3'-deoxy-3',4'-didehydro-CTP as an extremely efficient antiviral nucleotide.-
dc.languageeng-
dc.publisherOxford University Press for Society for Molecular Biology and Evolution. The Journal's web site is located at http://gbe.oxfordjournals.org-
dc.relation.ispartofGenome Biology and Evolution-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectABCE1-
dc.subjectcytoophidia-
dc.subjectMaxwell's demon-
dc.subjectNsp1-
dc.subjectphosphoribosyltransferase-
dc.titleA Path toward SARS-CoV-2 Attenuation: Metabolic Pressure on CTP Synthesis Rules the Virus Evolution-
dc.typeArticle-
dc.identifier.emailDanchin, A: adanchin@hkucc.hku.hk-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1093/gbe/evaa229-
dc.identifier.pmid33125064-
dc.identifier.pmcidPMC7665462-
dc.identifier.scopuseid_2-s2.0-85097570817-
dc.identifier.hkuros321217-
dc.identifier.volume12-
dc.identifier.spage2467-
dc.identifier.epage2485-
dc.identifier.isiWOS:000606568300021-
dc.publisher.placeUnited Kingdom-

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