The IMPDH inhibitor merimepodib suppresses SARS-CoV-2 replication in vitro
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Abstract
The ongoing COVID-19 pandemic continues to pose a major public health burden around the world. The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over one million people worldwide as of April, 2020, and has led to the deaths of nearly 300,000 people. No approved vaccines or treatments in the USA currently exist for COVID-19, so there is an urgent need to develop effective countermeasures. The IMPDH inhibitor merimepodib (MMPD) is an investigational antiviral drug that acts as a noncompetitive inhibitor of IMPDH. It has been demonstrated to suppress replication of a variety of emerging RNA viruses. We report here that MMPD suppresses SARS-CoV-2 replication in vitro. After overnight pretreatment of Vero cells with 10 μM of MMPD, viral titers were reduced by 4 logs of magnitude, while pretreatment for 4 hours resulted in a 3-log drop. The effect is dose-dependent, and concentrations as low as 3.3 μM significantly reduced viral titers when the cells were pretreated prior to infection. The results of this study provide evidence that MMPD may be a viable treatment option for COVID-19.
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SciScore for 10.1101/2020.04.07.028589: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The virus was subsequently titrated and passaged once more on Vero cells, grown in DMEM supplemented with 5% FBS and 1% penicillin and streptomycin solution. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)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 …SciScore for 10.1101/2020.04.07.028589: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The virus was subsequently titrated and passaged once more on Vero cells, grown in DMEM supplemented with 5% FBS and 1% penicillin and streptomycin solution. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)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.
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