Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase
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Abstract
The ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. Here we show that Favipiravir exerts an antiviral effect as a nucleotide analogue through a combination of chain termination, slowed RNA synthesis and lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.
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SciScore for 10.1101/2020.05.15.098731: (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. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources In vitro infection assays: Cell line: VeroE6 (ATCC CRL-1586) cells were grown in minimal essential medium (Life Technologies) with 7.5% heat-inactivated fetal calf serum (FCS), at 37 °C with 5 % CO2 with 1 % penicillin/streptomycin (PS, 5000 U.mL-1 and 5000 μg.mL-1respectively; VeroE6suggested: NoneSoftware and Algorithms Sentences Resources The intensity of each band was quantified using the ImageQuant software (GE Healthcare)/Image … SciScore for 10.1101/2020.05.15.098731: (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. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources In vitro infection assays: Cell line: VeroE6 (ATCC CRL-1586) cells were grown in minimal essential medium (Life Technologies) with 7.5% heat-inactivated fetal calf serum (FCS), at 37 °C with 5 % CO2 with 1 % penicillin/streptomycin (PS, 5000 U.mL-1 and 5000 μg.mL-1respectively; VeroE6suggested: NoneSoftware and Algorithms Sentences Resources The intensity of each band was quantified using the ImageQuant software (GE Healthcare)/Image Gauge (Fuji) and/or using ImageJ as implemented in the Fiji package, with background subtraction. ImageQuantsuggested: (ImageQuant, RRID:SCR_014246)GE Healthcare)/Imagesuggested: NoneImageJsuggested: (ImageJ, RRID:SCR_003070)Fijisuggested: (Fiji, RRID:SCR_002285)Antiviral experiments data were analyzed using GraphPad Prism 7 software (Graph pad software) GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Quasi species with frequency over 0.1% were studied. Quasisuggested: NoneResults 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.
- 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.
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