Structural analysis of the SARS-CoV-2 methyltransferase complex involved in coronaviral RNA cap creation
This article has been Reviewed by the following groups
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
- Evaluated articles (ScreenIT)
Abstract
COVID-19 pandemic is caused by the SARS-CoV-2 virus that has several enzymes that could be targeted by antivirals including a 2’-O RNA methyltransferase (MTase) that is involved in the viral RNA cap formation; an essential process for RNA stability. This MTase is composed of two nonstructural proteins, the nsp16 catalytic subunit and the activating nsp10 protein. We have solved the crystal structure of the nsp10-nsp16 complex bound to the pan-MTase inhibitor sinefungin in the active site. Based on the structural data we built a model of the MTase in complex with RNA that illustrates the catalytic reaction. A structural comparison to the Zika MTase revealed low conservation of the catalytic site between these two RNA viruses suggesting preparation of inhibitors targeting both these viruses will be very difficult. Together, our data will provide the information needed for structure-based drug design.
Article activity feed
-
SciScore for 10.1101/2020.05.15.097980: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources The structure was solved by molecular replacement (nps10-nsp16 complex PDB ID 6W4H as the search model) and further refined in Phenix [25] and Coot [26] to good R-factors (Rwork = 18.05% and Rfree = 20.86%) and good geometry as summarized in Table 1. Phenixsuggested: (Phenix, RRID:SCR_014224)Cootsuggested: (Coot, RRID:SCR_014222)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques …SciScore for 10.1101/2020.05.15.097980: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources The structure was solved by molecular replacement (nps10-nsp16 complex PDB ID 6W4H as the search model) and further refined in Phenix [25] and Coot [26] to good R-factors (Rwork = 18.05% and Rfree = 20.86%) and good geometry as summarized in Table 1. Phenixsuggested: (Phenix, RRID:SCR_014224)Cootsuggested: (Coot, RRID:SCR_014222)Results from OddPub: Thank you for sharing your data.
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.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
-
