A Novel Protein Drug, Novaferon, as the Potential Antiviral Drug for COVID-19
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Abstract
Background
Novaferon, a novel protein drug approved for the treatment of chronic hepatitis B in China, exhibits potent antiviral activities. We aimed to determine the anti-SARS-CoV-2 effects of Novaferon in vitro, and conducted a randomized, open-label, parallel group study to explore the antiviral effects of Novaferon for COVID-19.
Methods
In laboratory, the inhibition of Novaferon on viral replication in cells infected with SARS-CoV-2, and on SARS-CoV-2 entry into healthy cells was determined. Antiviral effects of Novaferon were evaluated in COVID-19 patients with treatment of Novaferon, Novaferon plus Lopinavir/Ritonavir, or Lopinavir/Ritonavir. The primary endpoint was the SARS-CoV-2 clearance rates on day 6 of treatment, and the secondary endpoint was the time to the SARS-CoV-2 clearance in COVID-19 patients
Results
Novaferon inhibited the viral replication in infected cells (EC 50 =1.02 ng/ml), and protected healthy cells from SARS-CoV-2 infection (EC 50 =0.1 ng/ml). Results from the 89 enrolled COVID-19 patients showed that both Novaferon and Novaferon plus Lopinavir/Ritonavir groups had significantly higher SARS-CoV-2 clearance rates on day 6 than the Lopinavir/Ritonavir group (50.0% vs.24.1%, p = 0.0400, and 60.0% vs.24.1%, p = 0.0053). Median time to SARS-CoV-2 clearance were 6 days, 6 days, and 9 days for three groups respectively, suggesting a 3-dayreduction of time to SARS-CoV-2 clearance in both Novaferon and Novaferon plus Lopinavir/Ritonavir groups compared with Lopinavir/Ritonavir group.
Conclusions
Novaferon exhibited anti-SARS-CoV-2 effects in vitro and in COVID-19 patients. These data justified the further evaluation of Novaferon.
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SciScore for 10.1101/2020.04.24.20077735: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization Clinical Study: Trial design and treatments: This was a randomized, open-label, parallel group study. 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 cytotoxicity of Novaferon on Vero E6 cells was assessed, and the half-maximal cytotoxic concentration (CC50) of Novaferon on Vero Cells was determined by observing the cytopathic effects (CPE) of Novaferon. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)We further observed whether the previous treatment of Vero E6 cells with … SciScore for 10.1101/2020.04.24.20077735: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization Clinical Study: Trial design and treatments: This was a randomized, open-label, parallel group study. 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 cytotoxicity of Novaferon on Vero E6 cells was assessed, and the half-maximal cytotoxic concentration (CC50) of Novaferon on Vero Cells was determined by observing the cytopathic effects (CPE) of Novaferon. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)We further observed whether the previous treatment of Vero E6 cells with Novaferon protected the cells from viral entry through exposure of the pre-treated cells to SARS-CoV-2 later. Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources Lopinavir/Ritonavir (Kaletra) was manufactured by AbbVie Inc. AbbViesuggested: (AbbVie, RRID:SCR_010484)The peak levels of SARS virus were around 10 days after onset and then the viral level began to decrease without effective antiviral treatment in SARS patients[14]. SARSsuggested: 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: We detected the following sentences addressing limitations in the study:Limitations of this study: Our study has several limitations. First, all observations were done at one hospital in one city. Second, the sample size was relatively small and was not based on statistical consideration as limited by the availability of COVID-19 patients in Changsha city. Third, the unexpected difficulties associated with the COVID-19 outbreak compromised the quality of this study. For example, it’s highly possible that adverse events were under-reported due to the lack of medical staff and the risk situation. However, these limitations shouldn’t change the overall conclusion for thisrandomized trial because the antiviral assessments were strictly performed according to a vigorous standard.
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.
- 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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