Host-directed therapy with 2-deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2

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1. Version published to 10.1016/j.jve.2022.100305

   Dec 1, 2022
2. 

   ScreenIT

   May 27, 2022

   SciScore for 10.1101/2022.05.24.493068: (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
   Cell culture: Cells were seeded in 24-well tissue culture plates and incubated at 37 °C in media and densities (cells per well) for the given times as indicated below; human nasal epithelial cells (HNECs) in HNEC medium at 4.5×104 (72 h) and HeLa Ohio cells in HeLa Ohio medium at 2×105 (16-20 h).	HeLa suggested: None
   LLC-MK2 and MRC-5 cells were cultured in T25 cell culture flasks in the corresponding media at densities of 8×105 and 9×105, respectively.	MRC-5 suggested:…

   SciScore for 10.1101/2022.05.24.493068: (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
   Cell culture: Cells were seeded in 24-well tissue culture plates and incubated at 37 °C in media and densities (cells per well) for the given times as indicated below; human nasal epithelial cells (HNECs) in HNEC medium at 4.5×104 (72 h) and HeLa Ohio cells in HeLa Ohio medium at 2×105 (16-20 h).	HeLa suggested: None
   LLC-MK2 and MRC-5 cells were cultured in T25 cell culture flasks in the corresponding media at densities of 8×105 and 9×105, respectively.	MRC-5 suggested: None
   Virus titration: Samples from SARS-CoV-2, HCoV-229E and HCoV-NL63 were titrated on Vero cells, MRC-5 cells, and LLC-MK2 cells, respectively.	Vero suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059) LLC-MK2 suggested: BCRJ Cat# 0146, RRID:CVCL_3009)
   Titration was performed using eightfold replicates of serial half-log10 (for SARS-CoV-2, HCoV-229E and HCoV-NL63) or log10 (for RV-B14) dilutions of virus-containing samples followed by incubation at 36 °C (SARS-CoV-2, HCoV-229E), 33 °C (HCoV-NL63) and 34 °C (RV-B14) for 5-7 days (SARS-CoV-2, HCoV-229E, RV-B14) or 9-11 days (HCoV-NL63).	HCoV-229E suggested: JCRB Cat# JCRB1838, RRID:CVCL_B3M4)

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   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).

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   Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

   As conventional RT-PCR holds limitations to detect the negative strand in excess of positive strand copies, we employed a recently published strategy by Wiehler and Proud [32] to analyze the negative strand level. We observed that 2-DG significantly reduced the genomic (+)ssRNA as well as the template (-)ssRNA, a likely cause for the measured significant reduction in detectable extracellular viral RNA (Figure 4A&B). These findings point at a 2-DG-mediated impairment in viral RNA replication and amount of released virus. In line with this, titration of the released virus on HeLa Ohio cells showed a reduction in viral load (Figure 4C). To be noted, HeLa Ohio cells used in this experimental setup, due to their cancerous origin, have a high glucose demand and are especially sensitive to glucose starvation and 2-DG treatment. Therefore, low amounts of 2-DG were used, and the cells were treated only once after the start of the RV infection. This could explain the relatively small difference in viral load (Figure 4C) in contrast to the significant difference in released extracellular viral RNA (Figure 4B). In our subsequent analysis, we found that 2-DG exerted a protective effect by significantly reducing virus-induced cell death in HeLa Ohio cells (Figure 4D). In contrast, RV infection does not cause cell lysis in cultures of healthy bronchial epithelial cells [39]. Interestingly, the same study reported increased viral replication and cell lysis after RV infection in asthmatic bro...

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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   Results from JetFighter: We did not find any issues relating to colormaps.

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   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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   Results from scite Reference Check: We found no unreliable references.

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3. 

   Version published to 10.1101/2022.05.24.493068 on bioRxiv

   May 24, 2022