RR:C19 Evidence Scale rating by reviewer:
Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.
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Review:
In their research article, the authors assert that glutamine metabolism plays an important role in the replication of the coronavirus virus family within mammalian cell systems. Employing transcriptomics, proteomics, and metabolomics methodologies, their study reveals a compelling positive correlation between heightened glutamine metabolism and the replication of coronaviruses.
Major concerns:
The overall quality of the uploaded figures is problematic, which significantly decrease the clarity and comprehensibility of the review. Several issues with specific figures further compound these problems, including:
Figures 1A and 1B display blurry and pixelated patterns.
Figure 1D is cut off at one edge, and the legends fail to elucidate the significance of numbers 1 and 8.
Figure 1H lacks a length scale for microscopic observations.
Figure 1L is lacking a legend.
Figure 4I requires re-uploading at a higher resolution.
Moreover, specific claims within the figures and text require critical attention:
In Figure 1D, the justification for the lack of GSL2 expression is problematic. Given that HBEC are bronchial epithelial cells and GSL2 is predominantly expressed in the liver, pancreas, and brain, it is expected to have low to no expression in pulmonary tissues. This needs to be justified in a better way.
For Figures 1E and 1G, it is evident that the authors did not conduct statistical analyses prior to drawing their conclusions. The absence of statistical rigor weakens the overall scientific validity.
Figures 1J and 1K are cited in the text to demonstrate the temporal RNA transcript levels association between GLS transcripts and viral transcripts OC43. However, a discrepancy arises in Figure 1J and 1K, where GLS RNA levels and viral RNA do not overlap at 12hpi. This result necessitates a detailed justification.
Figure 4J is discussed in the text as showing the effects of UP4 treatment on various parameters. The description mentions the abolition of the increases in glutamate, downstream TCA cycle intermediates, and aspartate during OC43 infection, as well as nucleosides and nucleotides. However, upon careful examination of the heatmap, it becomes clear that only nucleosides exhibit an abolition of the increase in the infected +UP4 conditions. This observation should be reflected in the figure's description.
Minor Concerns
The absence of line numbers in the preprint is making it challenging for reviewers to provide precise feedback or point out specific concerns. Adding line numbers to the document would facilitate the review process.
Figure 1M: The preprint mentioned Figure 1M in the figure legend, but the figure itself is missing. To ensure completeness and consistency, it's crucial to include Figure 1M as described in the legend.
Figure 4J Experiment Design: It's suggested that the experiment design for Figure 4J could benefit from including a control uninfected condition with UP4 to understand the impact of UP4 on uninfected cells.
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