Pyronaridine and artesunate are potential antiviral drugs against COVID-19 and influenza
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Abstract
Since the first human case was reported in Wuhan Province, China in December 2019, SARS-CoV-2 has caused millions of human infections in more than 200 countries worldwide with an approximately 4.01% case-fatality rate (as of 27 July, 2020; based on a WHO situation report), and COVID-19 pandemic has paralyzed our global community. Even though a few candidate drugs, such as remdesivir (a broad antiviral prodrug) and hydroxychloroquine, have been investigated in human clinical trials, their therapeutic efficacy needs to be clarified further to be used to treat COVID-19 patients. Here we show that pyronaridine and artesunate, which are the chemical components of anti-malarial drug Pyramax ® , exhibit antiviral activity against SARS-CoV-2 and influenza viruses. In human lung epithelial (Calu-3) cells, pyronaridine and artesunate were highly effective against SARS-CoV-2 while hydroxychloroquine did not show any effect at concentrations of less than 100 μM. In viral growth kinetics, both pyronaridine and artesunate inhibited the growth of SARS-CoV-2 and seasonal influenza A virus in Calu-3 cells. Taken together, we suggest that artesunate and pyronaridine might be effective drug candidates for use in human patients with COVID-19 and/or influenza, which may co-circulate during this coming winter season.
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SciScore for 10.1101/2020.07.28.225102: (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 Serial two-fold dilution from 50 μM to 1.56 μM of chemicals were added to the cell supernatants, and the cell supernatants were harvested at 24, 48, and 72 hpi for virus titration by the plaque assay in Vero cells. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Yield reduction of influenza virus: Monolayered Calu-3 cells was inoculated with influenza virus at a 0.1 MOI for 1 h. Calu-3suggested: KCLB Cat# 30055, RRID:CVCL_0609)S… SciScore for 10.1101/2020.07.28.225102: (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 Serial two-fold dilution from 50 μM to 1.56 μM of chemicals were added to the cell supernatants, and the cell supernatants were harvested at 24, 48, and 72 hpi for virus titration by the plaque assay in Vero cells. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Yield reduction of influenza virus: Monolayered Calu-3 cells was inoculated with influenza virus at a 0.1 MOI for 1 h. Calu-3suggested: KCLB Cat# 30055, RRID:CVCL_0609)Serial two-fold dilution from 12.5 μM to 1.56 μM of pyronaridine, artesunate, or oseltamivir carboxylate were added to the cell supernatants, and the cell supernatants were harvested at 24, 48, and 72 hpi for virus titration by the plaque assay in MDCK cells. MDCKsuggested: CLS Cat# 602280/p823_MDCK_(NBL-2, RRID:CVCL_0422)Software and Algorithms Sentences Resources 50% inhibitory concentration (IC50) of pyronaridine, artesunate, or hydroxychloroquine was calculated using GraphPad Prism 8 (GraphPad, San Diego, CA) GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)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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SciScore for 10.1101/2020.07.28.225102: (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 Vero, Calu-3, and Madin-Darby canine kidney (MDCK) cells were purchase from the Korean Cell Line Bank (Seoul, Republic of Korea). Calu-3suggested: BCRJ Cat# 0264, RRID:CVCL_0609Influenza A(H1N1) virus (A/Korea/01/2009, NCBI:txid644289) was prepared by propagation in MDCK cells after plaque purification. … SciScore for 10.1101/2020.07.28.225102: (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 Vero, Calu-3, and Madin-Darby canine kidney (MDCK) cells were purchase from the Korean Cell Line Bank (Seoul, Republic of Korea). Calu-3suggested: BCRJ Cat# 0264, RRID:CVCL_0609Influenza A(H1N1) virus (A/Korea/01/2009, NCBI:txid644289) was prepared by propagation in MDCK cells after plaque purification. MDCKsuggested: CLS Cat# 602280/p823_MDCK_(NBL-2), RRID:CVCL_0422Monolayered Vero cells prepared in advance was inoculated with the virusinfected cell supernatants. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059Software and Algorithms Sentences Resources 50% inhibitory concentration (IC50) of pyronaridine, artesunate, or hydroxychloroquine was calculated using GraphPad Prism 8 (GraphPad, San Diego, CA) GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)After 2 h, the cell viability was measured, and 50% cytotoxic concentration (CC50) was calculated using GraphPad Prism 8 (GraphPad). 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 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.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
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SciScore for 10.1101/2020.07.28.225102: (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 In human lung epithelial (Calu-3) cells, pyronaridine and artesuna were highly effective against SARS-CoV-2 while hydroxychloroquine did not show any effect at concentrations of less than 100 μM. Calu-3suggested: BCRJ Cat# 0264, CVCL_0609The mode of action described above is consistent with our data, which indicate that the antiviral efficacy of artesunate … SciScore for 10.1101/2020.07.28.225102: (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 In human lung epithelial (Calu-3) cells, pyronaridine and artesuna were highly effective against SARS-CoV-2 while hydroxychloroquine did not show any effect at concentrations of less than 100 μM. Calu-3suggested: BCRJ Cat# 0264, CVCL_0609The mode of action described above is consistent with our data, which indicate that the antiviral efficacy of artesunate against SARS-CoV-2 in Calu-3 cells is far superior to that in Vero cells, which are well known for their type-1 IFN pathway deficiency. Verosuggested: CLS Cat# 605372/p622_VERO, CVCL_0059For the H1N1 influenza virus, MDCK cells were used, instead of Vero cells Combination therapy. MDCKsuggested: CLS Cat# 602280/p823_MDCK_(NBL-2), CVCL_0422Software and Algorithms Sentences Resources Our data demonstrate a new possibility of repurposing antimalarial drugs against both SARS-CoV-2 and influenza A viruses. SARS-CoV-2suggested: (Active Motif Cat# 91345, AB_2847847)50% inhibitory concentration (IC50) of pyronaridine, artesunate, or hydroxychloroquine was calculated using GraphPad Prism 8 (GraphPad, San Diego, CA) GraphPadsuggested: (GraphPad Prism, SCR_002798)After 2 h, the cell viability was measured, and 50% cytotoxic concentration (CC50) was calculated using GraphPad Prism 8 (GraphPad). GraphPad Prismsuggested: (GraphPad Prism, SCR_002798)Data from additional tools added to each annotation on a weekly basis.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
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