Clinical Efficacy of Fufang Yinhua Jiedu (FFYH) Granules in Mild COVID-19 and Its Anti-SARS-CoV-2 Mechanism by Blocking Autophagy Through Inhibiting the AKT/mTOR Signaling Pathway

Overview

Journal Front Pharmacol

Date 2024 Oct 1

PMID 39351097

Authors

Wenlei Wang

Zhihui Zheng

Xiaoyuan Qi

Hailin Wei

Xuhua Mao

Qin Su

Xiang Chen

Yan Feng

Guohong Qiao

Tieliang Ma

Zhian Tang

Guangming Zhou

Jinqiang Zhuang

Pinghu Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Fufang Yinhua Jiedu (FFYH) granules are recommended for treating coronavirus pneumonia (COVID-19) 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.

Materials And Methods: 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 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 ( < 0.05). No patients progressed to severe or critical cases.

Conclusion: Our results indicate that FFYH not only has good anti-viral 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.

References

Fernandes M, Barata J . IL-7 and IL-7R in health and disease: An update through COVID times. Adv Biol Regul. 2022; 87:100940. DOI: 10.1016/j.jbior.2022.100940. View

Jiang Y, Rubin L, Peng T, Liu L, Xing X, Lazarovici P . Cytokine storm in COVID-19: from viral infection to immune responses, diagnosis and therapy. Int J Biol Sci. 2022; 18(2):459-472. PMC: 8741849. DOI: 10.7150/ijbs.59272. View

Yang Y, Shen C, Li J, Yuan J, Wei J, Huang F . Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19. J Allergy Clin Immunol. 2020; 146(1):119-127.e4. PMC: 7189843. DOI: 10.1016/j.jaci.2020.04.027. View

Kramer B, Knoll R, Bonaguro L, ToVinh M, Raabe J, Astaburuaga-Garcia R . Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19. Immunity. 2021; 54(11):2650-2669.e14. PMC: 8416549. DOI: 10.1016/j.immuni.2021.09.002. View

Zhang W, Zhang Z, Ye Y, Luo Y, Pan S, Qi H . Lymphocyte percentage and hemoglobin as a joint parameter for the prediction of severe and nonsevere COVID-19: a preliminary study. Ann Transl Med. 2020; 8(19):1231. PMC: 7607120. DOI: 10.21037/atm-20-6001. View

Michot J, Albiges L, Chaput N, Saada V, Pommeret F, Griscelli F . Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: a case report. Ann Oncol. 2020; 31(7):961-964. PMC: 7136869. DOI: 10.1016/j.annonc.2020.03.300. View

Zhang L, Wu L, Xu X, Yuan Y, Jiang R, Yan X . Effectiveness of Lianhua Qingwen Capsule in Treatment of Asymptomatic COVID-19 Patients: A Randomized, Controlled Multicenter Trial. J Integr Complement Med. 2022; 28(11):887-894. DOI: 10.1089/jicm.2021.0352. View

Lyu M, Fan G, Xiao G, Wang T, Xu D, Gao J . Traditional Chinese medicine in COVID-19. Acta Pharm Sin B. 2021; 11(11):3337-3363. PMC: 8450055. DOI: 10.1016/j.apsb.2021.09.008. View

Gassen N, Papies J, Bajaj T, Emanuel J, Dethloff F, Chua R . SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals. Nat Commun. 2021; 12(1):3818. PMC: 8217552. DOI: 10.1038/s41467-021-24007-w. View

10.

Zizzo G, Tamburello A, Castelnovo L, Laria A, Mumoli N, Faggioli P . Immunotherapy of COVID-19: Inside and Beyond IL-6 Signalling. Front Immunol. 2022; 13:795315. PMC: 8948465. DOI: 10.3389/fimmu.2022.795315. View

11.

Djakpo D, Wang Z, Zhang R, Chen X, Chen P, Antoine M . Blood routine test in mild and common 2019 coronavirus (COVID-19) patients. Biosci Rep. 2020; 40(8). PMC: 7414516. DOI: 10.1042/BSR20200817. View

12.

Zhang X, Yuan H, Yang Z, Hu X, Mahmmod Y, Zhu X . SARS-CoV-2: An Updated Review Highlighting Its Evolution and Treatments. Vaccines (Basel). 2022; 10(12). PMC: 9780920. DOI: 10.3390/vaccines10122145. View

13.

Aliyari S, Ghaffari A, Pernet O, Parvatiyar K, Wang Y, Gerami H . Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2. Acta Pharm Sin B. 2022; 12(4):1624-1635. PMC: 8883762. DOI: 10.1016/j.apsb.2022.02.019. View

14.

Dharra R, Sharma A, Datta S . Emerging aspects of cytokine storm in COVID-19: The role of proinflammatory cytokines and therapeutic prospects. Cytokine. 2023; 169:156287. PMC: 10291296. DOI: 10.1016/j.cyto.2023.156287. View

15.

Zhang D, Zhang B, Lv J, Sa R, Zhang X, Lin Z . The clinical benefits of Chinese patent medicines against COVID-19 based on current evidence. Pharmacol Res. 2020; 157:104882. PMC: 7198419. DOI: 10.1016/j.phrs.2020.104882. View

16.

Zhu Y, Chen D, Zhu Y, Ge X, Li Z, Miao H . Clinical observation of glucocorticoid therapy for critically ill patients with COVID-19 pneumonia. J Int Med Res. 2023; 51(2):3000605221149292. PMC: 9972059. DOI: 10.1177/03000605221149292. View

17.

Wang C, Wang H, Liu X, Xu D, Tang Y, Luo P . Traditional Chinese medicine for the treatment of influenza: a systematic review and meta-analysis of randomized controlled trials. J Tradit Chin Med. 2014; 34(5):527-31. DOI: 10.1016/s0254-6272(15)30057-1. View

18.

Algassim A, Elghazaly A, Alnahdi A, Mohammed-Rahim O, Alanazi A, Aldhuwayhi N . Prognostic significance of hemoglobin level and autoimmune hemolytic anemia in SARS-CoV-2 infection. Ann Hematol. 2020; 100(1):37-43. PMC: 7486165. DOI: 10.1007/s00277-020-04256-3. View

19.

Li J, Wang R, Guo W, Li J . Efficacy and safety of traditional Chinese medicine for the treatment of influenza A (H1N1): A meta-analysis. J Chin Med Assoc. 2016; 79(5):281-91. DOI: 10.1016/j.jcma.2015.10.009. View

20.

Shen P, Li J, Tu S, Wu Y, Peng Y, Chen G . Positive effects of Lianhuaqingwen granules in COVID-19 patients: A retrospective study of 248 cases. J Ethnopharmacol. 2021; 278:114220. PMC: 8139441. DOI: 10.1016/j.jep.2021.114220. View