Inhibitors of L-type calcium channels show therapeutic potential for treating SARS-CoV-2 infections by preventing virus entry and spread
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Abstract
COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2). The virus is responsible for an ongoing pandemic and concomitant public health crisis around the world. While vaccine development is proving to be highly successful, parallel drug development approaches are also critical in the response to SARS-CoV-2 and other emerging viruses. Coronaviruses require Ca 2+ ions for host cell entry and we have previously shown that Ca 2+ modulates the interaction of the viral fusion peptide with host cell membranes. In an attempt to accelerate drug development, we tested a panel of L-type calcium channel blocker (CCB) drugs currently developed for other conditions, to determine whether they would inhibit SARS-CoV-2 infection in cell culture. All the CCBs tested showed varying degrees of inhibition, with felodipine and nifedipine strongly limiting SARS-CoV-2 entry and infection in epithelial lung cells at concentrations where cell toxicity was minimal. Further studies with pseudo-typed particles displaying the SARS-CoV-2 spike protein suggested that inhibition occurs at the level of virus entry. Overall, our data suggest that certain CCBs have potential to treat SARS-CoV-2 infections and are worthy of further examination for possible treatment of COVID-19.
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SciScore for 10.1101/2020.07.21.214577: (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 SARS-CoV-2 infections and TCID50 assays: Vero E6 and Calu-3 cells were grown to confluency under biosafety level-2 (BSL-2) conditions. Calu-3suggested: KCLB Cat# 30055, RRID:CVCL_0609)Undiluted and diluted samples were then added to the Vero E6 cells and grown for 72 hours at 37° C and 5% CO2. Vero E6suggested: NoneFor PP production, HEK 293T cells were transfected with pCDNA3.1/SARS-CoV-2 S Wuhan Hu-1 to generate SARS-CoV-2 S carrying … SciScore for 10.1101/2020.07.21.214577: (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 SARS-CoV-2 infections and TCID50 assays: Vero E6 and Calu-3 cells were grown to confluency under biosafety level-2 (BSL-2) conditions. Calu-3suggested: KCLB Cat# 30055, RRID:CVCL_0609)Undiluted and diluted samples were then added to the Vero E6 cells and grown for 72 hours at 37° C and 5% CO2. Vero E6suggested: NoneFor PP production, HEK 293T cells were transfected with pCDNA3.1/SARS-CoV-2 S Wuhan Hu-1 to generate SARS-CoV-2 S carrying PPs. HEK 293Tsuggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)Software and Algorithms Sentences Resources Data was analyzed using Microsoft Excel and GraphPad Prism 8. Microsoft Excelsuggested: (Microsoft Excel, RRID:SCR_016137)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
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.
- 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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