Abstract
The coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), has spread worldwide, affecting over 250 million people and resulting in over five million deaths. Antivirals that are effective are still limited. The antiviral activities of the Petasites hybdridus CO2 extract Ze 339 were previously reported. Thus, to assess the anti-SARS-CoV-2 activity of Ze 339 as well as isopetasin and neopetasin as major active compounds, a CPE and plaque reduction assay in Vero E6 cells was used for viral output. Antiviral effects were tested using the original virus (Wuhan) and the Delta variant of SARS-CoV-2. The antiviral drug remdesivir was used as control. Pre-treatment with Ze 339 in SARS-CoV-2-infected Vero E6 cells with either virus variant significantly inhibited virus replication with IC50 values of 0.10 and 0.40 μg/mL, respectively. The IC50 values obtained for isopetasin ranged between 0.37 and 0.88 μM for both virus variants, and that of remdesivir ranged between 1.53 and 2.37 μM. In conclusion, Ze 339 as well as the petasins potently inhibited SARS-CoV-2 replication in vitro of the Wuhan and Delta variants. Since time is of essence in finding effective treatments, clinical studies will have to demonstrate if Ze339 can become a therapeutic option to treat SARS-CoV-2 infections.
Highlights
IntroductionCOVID-19 (coronavirus disease 2019) first appeared in China at the end of 2019 and has, since spread around the globe, causing more than 5 million deaths [1]
COVID-19 first appeared in China at the end of 2019 and has, since spread around the globe, causing more than 5 million deaths [1]
By visualization of the extent of the cytopathogenic effect (CPE) in the form of cytolytic plaque formation on Vero E6 cells when infected with a clinical strain of SARS-CoV-2, Wuhan
Summary
COVID-19 (coronavirus disease 2019) first appeared in China at the end of 2019 and has, since spread around the globe, causing more than 5 million deaths [1]. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly via droplets and aerosols (for review see [2]). The disease affects the upper respiratory tract and lungs, heart, liver, gastrointestinal tract, and other organs, but the majority of infections remains asymptomatic, and patients develop only mild symptoms [3]. Observations include lymphocytopenia; an increase in neutrophils; and increased serum levels of IL-1β, IL-2, IL-4, IL-6, IL-10, TNF-α, and interferonγ [3,5,6] This cytokine response ( referred to as ‘cytokine storm’) is associated with cellular injury, which in turn is reflected in increased serum levels of lactate dehydrogenase (LDH), cardiac and hepatic enzymes, and the activation of coagulation and fibrinolysis with markedly increased plasma levels of D-dimers, among others [3,5,6]. Several therapeutic strategies to target the hyperinflammation caused by an overactive cytokine response are currently being explored (for review see [13])
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