Glucosidase inhibitors suppress SARS-CoV-2 in tissue culture and may potentiate
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Abstract
Iminosugar glucosidase inhibitors prevent the folding of a range of viral N-linked glycoproteins, ranging from hepatitis B to Ebola. We recently showed they inhibit folding and function of the ACE2 protein, which is the receptor for SARS-CoV-2, and they have also inhibited the SARS Spike polypeptides. Here we report that the imino sugar glucosidase inhibitors, N-butyl deoxynojirimycin (NBDNJ), which is approved for management of lysosomal storage disease (sold as Zavesca), and ureido-N-hexyl deoxynojirimycine (BSBI-19029), suppress the replication of SARS-ncCoV-2/USA/WA1/2020 strain, in tissue culture. Moreover, combinations of either of these iminosugars with Remdesivir were particularly potent in suppressing SARS-CoV-2. Briefly, NBDNJ, 19029 and Remdesivir suppressed SARS-CoV-2 production in A549 ACE2 human lung cells with IC90s of ~130 μM, ~4.0 μM, and 0.006 μM respectively. The combination of as little as 0.037 μM of NBDNJ or 0.04 μM 19029, respectively and 0.002 μM Remdesivir yielded IC90s. Medical strategies to manage SARS-CoV-2 infection of people are urgently needed, and although Remdesivir and Favipiravir have shown efficacy, it is limited. NBDNJ was recently reported by others to have tissue culture activity against SARS-CoV-2, so our report confirms this, and extends the findings to a more potent iminosugar, 19029 and combination with Remdesivir. Since both NBDNJ and Remdesivir are both approved and available for human use, the possibility that NBDNJ has mono therapeutic value against SARS-CoV-2 as well as can enhance Remdesivir, may have clinical implications, which are discussed, here.
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SciScore for 10.1101/2021.05.14.444190: (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
Antibodies Sentences Resources After 48 hours, cells were stained with DAPI, and in the case of SARS-CoV-2 (USA-WA1/2020 strain) with anti nucleocapsid antibody. anti nucleocapsid antibody.suggested: NoneExperimental Models: Cell Lines Sentences Resources Cells and Virus: Human lung carcinoma A549ACE2 cells were maintained in DMEM made 10% FBS (Weston et al., 2020). A549ACE2suggested: NoneBoth viruses were propagated in Vero-E6 cells. Vero-E6suggested: NoneResults from OddPub: We did not detect open data. We also did not …
SciScore for 10.1101/2021.05.14.444190: (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
Antibodies Sentences Resources After 48 hours, cells were stained with DAPI, and in the case of SARS-CoV-2 (USA-WA1/2020 strain) with anti nucleocapsid antibody. anti nucleocapsid antibody.suggested: NoneExperimental Models: Cell Lines Sentences Resources Cells and Virus: Human lung carcinoma A549ACE2 cells were maintained in DMEM made 10% FBS (Weston et al., 2020). A549ACE2suggested: NoneBoth viruses were propagated in Vero-E6 cells. Vero-E6suggested: 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.
- 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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