Shufeng Jiedu, a promising herbal therapy for moderate COVID-19:Antiviral and anti-inflammatory properties, pathways of bioactive compounds, and a clinical real-world pragmatic study

XIA, Lu; SHI, Yujing; SU, Jie; Friedemann, Thomas; TAO, Zhenggang; Lu, Yunfei; LING, Yun; Lv, Ying; ZHAO, Ronghua; GENG, Zihan; CUI, Xiaolan; LU, Hongzhou; Schröder, Sven

BACKGROUND: Shufeng Jiedu capsules (SFJDC), a patented herbal drug composed of eight medicinal plants, is used for the treatment of different viral respiratory tract infectious diseases. Based on its antiviral, anti-inflammatory and immunoregulatory activity in acute lung injury, SFJDC might be a promising candidate for the treatment of COVID-19. PURPOSE: To evaluate the antiviral and anti-inflammatory properties and to discover the mechanism of action of SFJDC as a potential drug for the treatment of COVID-19. Furthermore, the study should determine the clinical effectiveness of SFJDC for the treatment of COVID-19. DESIGN: We analyzed the antiviral and anti-inflammatory effects of SFJDC in a HCoV-229E mouse model on lung index, virus load in the lung, the release of cytokines, and on T- and B-lymphocytes. The mechanism of action was further investigated by network analysis. Additionally, we investigated data from a clinical pragmatic real-world study for patients with confirmed COVID-19, to evaluate the clinical effect of SFJDC and to determine the best time to start the treatment. RESULTS: SFJDC significantly reduced the virus load in the lung of HCoV-229E mice (from 1109.29±696.75 to 0±0 copies/ml), decreased inflammatory factors IL-6, IL-10, TNF-α, and IFN-γ in the lung, and increased the amount of CD4(+) and CD8(+) cells in the blood compared to the model group. Network analysis revealed that SFJDC reduces the activity of NFκB via several signaling pathways. Quercetin, wogonin, and polydatin bind directly to the main protease (M(pro)) of SARS-CoV-2. Clinical data showed that SFJDC, added to standard antiviral therapy (AVD), significantly reduced the clinical recovery time of COVID-19 and fatigue (from 3.55±4.09 to 1.19±2.28 days) as well as cough (from 5.67±5.64 to 3.47±3.75) days compared to AVD alone. SFJDC therapy was significantly more effective when used within the first 8 days after the onset of symptoms. CONCLUSION: SFJDC might be a promising drug for the treatment of COVID-19, but large-scale randomized, double-blinded, placebo-controlled clinical trials are needed to complement the real-world evidence. It might be beneficial to start SFJDC treatment as early as possible in suspected cases of COVID-19.