Background: In December 2019, a novel coronavirus, SARS-CoV-2 caused a series of acute atypical respiratory diseases worldwide. However, there is still a lack of drugs with clear curative effects, and the clinical trial research of vaccines has not been completely finished.
Purpose: LH capsules are approved TCM patent medicine that are widely used for the treatment of respiratory tract infectious diseases caused by colds and flu. On April 12, 2020, LH capsules and granules were officially repurposed by the China Food and Drug Administration (CFDA) for patients with mild COVID-19 based on their safety and efficacy demonstrated through multicentre, randomized, controlled clinical trials. We hope to conduct a comprehensive review of it through modern pharmacy methods, and try to explain its possible mechanism.
Methods: Using the full names of LH capsules Lianhuaqingwen, Lianhua Qingwen andSARS-COV-2, COVID-19 as the keywords of the search terms, systemically search for existing related papers in various databases such as Web of Science and PubMed. And completed the collection of clinical data in ClinicalTrials.gov and Chinese Clinical Trial Registry. Last but not least, we have sorted out the anti-inflammatory and antiviral mechanisms of LH capsules through literature and Selleck.
Results: This review systematically sorted out the active ingredients in LH capsules. Furthermore, the related pharmacological and clinical trials of LH capsule on SARS-CoV-2, IAV and IBV were discussed in detail. Moreover, the present review provides the first summary of the potential molecular mechanism of specific substances in LH capsules involved in resistance to SARS-COV-2 infection and the inhibition of cytokine storm syndrome (CSS) caused by IL-6.
Conclusion: This review summarizes the available reports and evidence that support the use of LH capsules as potential drug candidates for the prevention and treatment of COVID-19. However, TCM exerts its effects through multiple targets and multiple pathways, and LH capsules are not an exception. Therefore, the relevant mechanisms need to be further improved and experimentally verified.
Keywords: 3C-like protease (3CLpro); 3CLpro, 3C-like protease; ACE2, Angiotensin-converting enzyme 2; AECOPD, Acute exacerbation of chronic obstructive pulmonary disease; AIDS, Acquired immune deficiency syndrome; AQP3, Aquaporins 3; ARDS, Acute respiratory distress syndrome; CAT, COPD assessment test; CC50, 50% Cytotoxic concentration; CCL-2/MCP-1, C—C motif ligand 2/monocyte chemoattractant protein-1; CFDA, China Food and Drug Administration; COPD, Chronic obstructive pulmonary disease; COVID-19; COVID-19, Coronavirus disease 2019; CPE, Cytopathic effect; CSS, Cytokine storm syndrome; CT, Computed tomography; CXCL-10/IP-10, C-X-C Motif Chemokine Ligand 10/ Interferon Gamma-induced Protein 10; Cytokine storm syndrome (CSS); DMSO, Dimethyl sulfoxide; E protein, Envelope protein; ERK, Extracellular signal-regulated kinase; FBS, Fatal bovine serum; Forsythia honeysuckle (Lianhuaqingwen,LH) capsules; Grb2, Growth factor receptor-bound protein 2; HIV, Human immunodeficiency virus; HPLC, High-performance liquid chromatography; HSV-1, Herpes simplex virus type 1; HVJ, Hemagglutinating virus of Japan; Hep-2, Human epithelial type 2; Huh-7, Human Hepatocellular Carcinoma-7; IAV, Influenza A virus; IBV, Influenza B virus; IC50, 50% Inhibition concentration; IFN-λ1, Interferon-λ1; IL-6, Interleukin-6; IL-6R, IL-6 Receptor; IL-8, Interleukin-8; IP-10, Interferon-inducible protein-10; JAK/STAT, Janus kinase/signal transducers and activators of transcription; JAK1/2, Janus kinase1/2; LD50, 50% Lethal dose; LH capsules, Forsythia honeysuckle (Lianhuaqingwen) capsules; M protein, Membrane protein; MAPK, Mitogen-activated protein kinase; MCP-1, Monocyte chemotactic protein 1; MDCK, Madin-darby canine kidney; MEK, Mitogen-activated protein kinase kinase; MERS, Middle east respiratory syndrome; MIP-1β, Macrophage Inflammatory Protein-1β; MLD50, 50% Minimum lethal dose; MOF, Multifunctional organ damage; MOI, Multiplicity of infection; MTT, Methyl Thiazolyl Tetrazolium; NF-kB, Nuclear transcription factor kappa-B; NHC, National Health Commission; ORFs, Open reading frames; PBS, Phosphate buffered saline; PHN, Phillyrin; PI3K, Phosphoinositide 3-kinases; PKA/p-CREB, Protein kinase A /phosphorylated cAMP response element-binding protein; PKB, Akt, Protein kinase B; PLpro, Papain-like proteases; PRC, People's Republic of China; QC, Quality control; RANTES, Regulated on activation normal T cell expressed and secreted; RSV, Respiratory syncytial virus; RT-PCR, Reverse transcription PCR; Ras, Ras GTPase; SARS-CoV-2; TCID50, 50% Tissue culture infective dose; TD0, Non-toxic Dose; TD50, Half-toxic dose; Vero E6, African Green Monkey Kidney Epithelial-6; gp-130, Glycoprotein 130; mIL-6R, Membrane-bound form IL-6 Receptor; mTOR, Mammalian target of rapamycin; nsps, Non-structural proteins; qPCR, Quantitative PCR.
© 2021 The Authors. Published by Elsevier B.V.