Antiviral activity of molnupiravir precursor NHC against SARS-CoV-2 Variants of Concern (VOCs) and its therapeutic window in a human lung cell model

SciScore for 10.1101/2021.11.23.469695: (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
) Human ACE2-A549 cells were grown to confluency and infected at an MOI of 0.1 in either DMEM with 2%FBS and 0.05mg/ml gentamicin, or in the same media containing 0.01µM, 0.1µM, 1µM or 10µM NHC by allowing virus to adsorb to cells in a volume of 100µl for one hour at 37°C, and then topping up to 500µl with the relevant media afterwards.	ACE2-A549 suggested: None
Results In order to find the appropriate concentration range of NHC in hACE2-A549 cells, to investigate the effect on viral biology, Cell-titer Glo Assay (Promega) were used to measure % ATP production in cells.	hACE2-A549 suggested: None
Software and Algorithms
Sentences	Resources
Primer-trimmed bam files were further analysed using DiversiTools (http://josephhughes.github.io/DiversiTools/) with the “-orfs” function to generate the ratio of amino acid change in the reads and coverage at each site of protein in comparison to the reference SARS-CoV-2 genome (MN908947.3).	DiversiTools suggested: None
The absolute IC50 values were calculated using GraphPad Prism 9, using a non-linear 4-parameter logistic regression in a dose-response curve.	GraphPad Prism suggested: (GraphPad Prism, RRID:SCR_002798)

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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:

However, in-vitro systems have several limitations in comparison to live models of infection, so results should be interpreted with care, although the mechanism of action will be intra-cellular. Use of molnupiravir in a Syrian hamster model infected with SARS-CoV-2 resulted in a drop in viral load and reduced lung pathology compared to controls Treatment 12 hours post-infection resulted in a protective effect 12 but not at 24 hours post- infection. Further work is required to delineate the true treatment window of the drug in humans with mild to moderate disease. Anti-viral drugs are best given early in infection to reduce viral load. In-vivo ferret models have shown that severity is linked to the size of the viral inoculum18. Therefore, molnupiravir likely acts to reduce disease by reducing viral load in patients, and potentially subsequently reducing transmission. 10,12. One of the main benefits of molnupiravir as opposed to remdesivir is that it can be administered orally. However, as was seen with the Influenza anti-viral, Tamiflu, resistance to anti-virals can develop rapidly develop resistance is necessary, though it is likely that any adaptation for resistance will correspond with a reduction in fitness as seen with remdesivir 20. Use of molnupiravir would likely be most beneficial if used in combination with another treatment, preferably targeting a different part of the viral life cycle as has been used with success for HIV treatment. Finally, molnupiravir has broad ...

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Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

Identifier	Status	Title
NCT04746183	Recruiting	AGILE (Early Phase Platform Trial for COVID-19)

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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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