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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1431617
This article is part of the Research Topic Immunomodulatory Natural Products - their Pharmacological and Therapeutic potential View all 4 articles

Clinical efficacy of Fufang Yinhua Jiedu (FFYH) granules in mild COVID-19 and its anti-SARS-CoV-2 mechanism by blocking autophagy through inhibiting AKT/mTOR signaling pathway

Provisionally accepted
Pinghu Zhang Pinghu Zhang 1*Wenlei Wang Wenlei Wang 1Zhihui Zheng Zhihui Zheng 1Xiaoyuan Qi Xiaoyuan Qi 2Hailin Wei Hailin Wei 1Xuhua Mao Xuhua Mao 2Qin Su Qin Su 1Xiang Chen Xiang Chen 2Yan Feng Yan Feng 2Guohong Qiao Guohong Qiao 2Tieliang Ma Tieliang Ma 2Zhian Tang Zhian Tang 2Guangming Zhou Guangming Zhou 2Jinqiang Zhuang Jinqiang Zhuang 3
  • 1 Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
  • 2 Yixing People's Hospital, Yixing, Jiangsu, China
  • 3 Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, China

The final, formatted version of the article will be published soon.

    Background: Fufang Yinhua Jiedu granules (FFYHs) are recommended for treating coronavirus pneumonia in China. However, its anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity and clinical efficacy against COVID-19 remain to be confirmed.Aims: Our study aimed to investigate the anti-SARS-CoV-2 effect and potential mechanism of FFYH.The activity of FFYH against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated via cell pathogenic effects, immunoblotting, immunofluorescence staining and qRT-PCR. The potential mechanism of FFYH against SARS-CoV-2 was investigated by immunoblotting. One head-to-head randomized controlled trial was designed to evaluate the clinical efficacy of FFYH in mild COVID-19. Two hundred patients were randomly recruited to receive either FFYH or LHQW (Lianhua Qingwen granules). Results: The in vitro results indicated that FFYH effectively inhibited SARS-CoV-2 replication by suppressing CPE and decreasing viral RNA and protein expression. A time-of-drug-addition assay confirmed that FFYH mainly targeted the binding and replication stages of the SARS-CoV-2 life cycle. Mechanistic studies revealed that blocking SARS-CoV-2-triggered autophagy may be the primary mechanism by which FFYH protects against SARS-CoV-2 infection by regulating the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Clinical results confirmed that FFYH effectively shortened the recovery time of clinical symptoms and viral nucleic acid negativity, improved abnormal hematology parameters and controlled excessive cytokine responses in mild COVID-19 patients. Subgroup analysis revealed that FFYH improved the recovery time of clinical symptoms, improved hematological parameters and controlled excessive cytokine storms to a greater extent in the mild COVID-19 male subgroup, abnormal hematology subgroup and 32-42-year-old subgroup than in the corresponding LHQW subgroup (P<0.05). No patients progressed to severe or critical cases. Conclusion: Our results indicate that FFYH not only has good antiviral activity against SARS-CoV-2 but also has significant efficacy against COVID-19, indicating that FFYH may be a novel complementary option for treating COVID-19.

    Keywords: COVID-19, Fufang Yinhua Jiedu granules, PI3K/AKT/mTOR, Cytokine storm, Autophagy

    Received: 12 May 2024; Accepted: 27 Aug 2024.

    Copyright: © 2024 Zhang, Wang, Zheng, Qi, Wei, Mao, Su, Chen, Feng, Qiao, Ma, Tang, Zhou and Zhuang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Pinghu Zhang, Medical College, Yangzhou University, Yangzhou, 225001, Jiangsu Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.