Biochemical and mathematical lessons from the evolution of the SARS-CoV-2 virus: paths for novel antiviral warfare
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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.
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SciScore for 10.1101/2020.07.31.230607: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Organisms/Strains Sentences Resources Since this model is nested in the first (3-parameter) model, we used as test statistic the likelihood ratio 2Δl = 2(l1 - l0), where l0 is the log-likelihood under assumption H0 (3-parameter TN93 model estimating all the elements of the tree) and 11 is the log-likelihood under assumption H1 (6-parameter TN93 model with local differentiation of the parameters downstream of a node of interest). l1 - l0suggested: NoneSoftware and Algorithms Sentences Resources We used program MAFFT [51] to generate these alignments. MAFFTsuggested: (MAFFT, RRID:SCR_011811)To this purpose, we … SciScore for 10.1101/2020.07.31.230607: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Organisms/Strains Sentences Resources Since this model is nested in the first (3-parameter) model, we used as test statistic the likelihood ratio 2Δl = 2(l1 - l0), where l0 is the log-likelihood under assumption H0 (3-parameter TN93 model estimating all the elements of the tree) and 11 is the log-likelihood under assumption H1 (6-parameter TN93 model with local differentiation of the parameters downstream of a node of interest). l1 - l0suggested: NoneSoftware and Algorithms Sentences Resources We used program MAFFT [51] to generate these alignments. MAFFTsuggested: (MAFFT, RRID:SCR_011811)To this purpose, we developed a Python script to modify the JSON file used as input by the Auspice program. Pythonsuggested: (IPython, RRID:SCR_001658)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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