In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance
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Abstract
In vitro selection of remdesivir-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed the emergence of a V166L substitution, located outside of the polymerase active site of the Nsp12 protein, after 9 passages of a single lineage. V166L remained the only Nsp12 substitution after 17 passages (10 μM remdesivir), conferring a 2.3-fold increase in 50% effective concentration (EC 50 ).
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SciScore for 10.1101/2022.02.07.479493: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources A WT SARS-CoV-2 isolate (D614G Spike + P323L nsp12 changes compared to WA1 strain) was passaged in Vero E6 cells initially in the presence of 1 µM of RDV and then increasing the drug concentration until clear virally-induced cytopathic effects were noted. Vero E6suggested: RRID:CVCL_XD71)Briefly, A549-hACE2 cells were seeded at 12,000 cells per well in medium containing 2% FBS into a white clear-bottom 96-well plate (Corning) at a volume of 50 µL and incubated … SciScore for 10.1101/2022.02.07.479493: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources A WT SARS-CoV-2 isolate (D614G Spike + P323L nsp12 changes compared to WA1 strain) was passaged in Vero E6 cells initially in the presence of 1 µM of RDV and then increasing the drug concentration until clear virally-induced cytopathic effects were noted. Vero E6suggested: RRID:CVCL_XD71)Briefly, A549-hACE2 cells were seeded at 12,000 cells per well in medium containing 2% FBS into a white clear-bottom 96-well plate (Corning) at a volume of 50 µL and incubated overnight at 37°C with 5% CO2. A549-hACE2suggested: RRID:CVCL_A5KB)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:- No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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