Due to the challenges for developing vaccines in devastating pandemic situations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing and screening of novel antiviral agents are peremptorily demanded. Herein, we developed EGYVIR as a potent immunomodulatory herbal extract with promising antiviral activity against SARS-CoV-2. It constitutes of a combination of black pepper extract with curcumin extract. The antiviral effect of EGYVIR extract is attributed to the two key phases of the disease in severe cases. First, the inhibition of the nuclear translocation of NF-kβ p50, attenuating the SARS-CoV-2 infection-associated cytokine storm. Additionally, the EGYVIR extract has an in vitro virucidal effect for SARS-CoV-2. The in vitro study of EGYVIR extract against SARS-CoV-2 on Huh-7 cell lines, revealed the potential role of NF-kβ/TNFα/IL-6 during the infection process. EGYVIR antagonizes the NF-kβ pathway in-silico and in-vitro studies. Consequently, it has the potential to hinder the release of IL-6 and TNFα, decreasing the production of essential cytokines storm elements.

Background: The SARS-COV-2 is a worldwide pandemic problem. We developed a herbal extract with potent in-vitro virucidal, anti-inflammatory and immunomodulatory effects called EGIVIR. Our aim is to assess the bioavailability and cytotoxicity of EGYVIR on different organs and biological systems in Sprague Dawley rats as a model of experimental animals. Methods: 128 rats were divided into 16 groups (8 rats each), where Egyvir was assessed in oral doses of 20, 30, and 40 mg/kg body weight, and by inhalation in 0.2, 0.3, and 0.4 mg/kg body weight, four times/day, compared to the control groups.   Results: The Egyvir had no significant effect on the blood pressure, pulse, motor activity, histological, hematological, and coagulation profiles. Also, the blood levels of triglycerides, cholesterol, blood glucose, lactate dehydrogenase (LDH), and creatine phosphor kinase (CPK) were not significantly affected. Egyvir had no harmful effect on the kidney and liver functions, blood electrolytes levels and urinary levels of sodium, potassium, and chloride. There was no significant effect on the serum levels of interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-10, interferon- γ (IFN-γ), and tumor necrosis factor- α (TNF-α). Additionally, there was no significant change in the levels of Superoxide dismutase (SOD), catalase, reduced glutathione (GSH), and malonaldehyde (MDA) in comparison to the control groups (P<0.05). Conclusion: Egyvir is considered a safe antiviral natural drug. It could be used for the treatment of SARS-COV-2 without any adverse effects when used with the recommended doses. However, these data are a preliminary step for validation in a clinical setting.