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Synergistic inhibition effects of andrographolide and baicalin on coronavirus mechanisms by downregulation of ACE2 protein level

Wan et al., Scientific Reports, doi:10.1038/s41598-024-54722-5
Feb 2024  
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In Vitro and mouse study showing that andrographolide and baicalin have synergistic antiviral effects against SARS-CoV-2. Andrographolide and baicalin inhibited binding between the SARS-CoV-2 spike protein and ACE2 receptor in human cells, and reduced ACE2 protein levels in lung tissues of SARS-CoV-2 infected mice. The combination reduced ACE2 protein synthesis in infected cells to a greater degree than either compound alone. In mice, andrographolide plus baicalin alleviated lung inflammation and cytokine storm triggered by the SARS-CoV-2 spike protein more effectively than individually. Additionally, andrographolide inhibited activity of the SARS-CoV-2 main protease in a dose-dependent manner, while baicalin did not. Authors suggest synergistic andrographolide and baicalin treatment could be a promising antiviral therapy against COVID-19 with multiple inhibitory mechanisms.
11 preclinical studies support the efficacy of andrographolide for COVID-19:
Wan et al., 21 Feb 2024, China, peer-reviewed, 8 authors. Contact: zengjinhao@cdutcm.edu.cn, zhaoziyi925@163.com, tangjy@cdutcm.edu.cn.
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Synergistic inhibition effects of andrographolide and baicalin on coronavirus mechanisms by downregulation of ACE2 protein level
Lina Wan, Yuchen Li, Wenhao Liao, Lizhen Lei, Maoyuan Zhao, Jinhao Zeng, Ziyi Zhao, Jianyuan Tang
Scientific Reports, doi:10.1038/s41598-024-54722-5
The SARS-CoV-2 virus, belonging to the Coronavirus genus, which poses a threat to human health worldwide. Current therapies focus on inhibiting viral replication or using anti-inflammatory/ immunomodulatory compounds to enhance host immunity. This makes the active ingredients of traditional Chinese medicine compounds ideal therapies due to their proven safety and minimal toxicity. Previous research suggests that andrographolide and baicalin inhibit coronaviruses; however, their synergistic effects remain unclear. Here, we studied the antiviral mechanisms of their synergistic use in vitro and in vivo. We selected the SARS-CoV-2 pseudovirus for viral studies and found that synergistic andrographolide and baicalein significantly reduced angiotensin-converting enzyme 2 protein level and viral entry of SARS-CoV-2 into cells compared to singal compound individually and inhibited the major protease activity of SARS-CoV-2. This mechanism is essential to reduce the pathogenesis of SARS-CoV-2. In addition, their synergistic use in vivo also inhibited the elevation of pro-inflammatory cytokines, including IL-6 and TNF-α-the primary cytokines in the development of acute respiratory distress syndrome (the main cause of COVID-19 deaths). In conclusion, this study shows that synergistic andrographolide and baicalein treatment acts as potent inhibitors of coronavirus mechanisms in vitro and in vivo-and is more effective together than in isolation. Since 2002, a zoonotic coronavirus that causes respiratory disease, including the severe acute respiratory syndromes coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus, and the recent 2019 SARS-CoV-2 has caused three outbreaks 1 . The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is the most significant global public health event with high pathogenicity and infectivity 2 . So far, hundreds of millions of test-positive cases and tens of thousands of deaths have been confirmed worldwide (https:// covid 19. who. int/) 3 . The Coronavirus genus includes SARS-CoV-2, which is an enveloped single-stranded positive-sense RNA virus with high pathogenicity. Its spike (S) protein mediates viral entry into host cells 2,4,5 , infecting human bronchial epithelial cells, upper respiratory tract cells, and lung cells, leading to irreversible lung damage, life-threatening respiratory diseases, and multi-organ failure 6 . Currently, there are no specific prevention or treatment methods available 4 . The genome RNA of SARS-CoV encodes a non-structural replicase polyprotein and structural proteins, including the S protein, nucleocapsid (N) protein, ion channel (E), and integral membrane (M) protein. The S protein is the most immunogenic of these proteins, and therefore related to vaccine development, diagnosis, and treatment 3,7 . The S protein consists of two subunits: the S1 subunit that binds to the host entry receptor angiotensin-converting enzyme 2 (ACE2) and the S2 subunit that mediates membrane fusion..
Author contributions L.W.: Methodology, performing the experiments, Formal analysis, Writing-original draft. Y.L.: Methodology, performing the experiments, Formal analysis. W.L.: Methodology, Formal analysis, Writing-review & editd. M.Z.: Methodology, performing the experiments, Formal analysis. L.L.: Methodology, performing the experiments, Formal analysis. J.Z.: Supervision. Z.Z.: Supervision. J.T.: Supervision, Writing-review & editing, Conceptualization, and coordinated the study. All authors have read and approved the final manuscript. Competing interests The authors declare no competing interests.
References
Banerjee, Perera, Tillekeratne, Potential SARS-CoV-2 main protease inhibitors, Drug Discov. Today, doi:10.1016/j.drudis.2020.12.005
Battagello, Unpuzzling COVID-19: Tissue-related signaling pathways associated with SARS-CoV-2 infection and transmission, Clin. Sci, doi:10.1042/cs20200904
Chang, Hou, Chang, Hsiao, Huang, The SARS coronavirus nucleocapsid protein-forms and functions, Antiviral Res, doi:10.1016/j.antiviral.2013.12.009
Chen, Ma, Chang, SARS-CoV-2 and the nucleus, Int. J. Biol. Sci, doi:10.7150/ijbs.72482
Choudhary, Sharma, Silakari, The interplay between inflammatory pathways and COVID-19: A critical review on pathogenesis and therapeutic options, Microb. Pathog, doi:10.1016/j.micpath.2020.104673
Cuervo, Grandvaux, ACE2: Evidence of role as entry receptor for SARS-CoV-2 and implications in comorbidities, doi:10.7554/eLife.61390
Ding, Elucidation of the mechanism of action of ginseng against acute lung injury/acute respiratory distress syndrome by a network pharmacology-based strategy, Front. Pharmacol, doi:10.3389/fphar.2020.611794
Drożdżal, An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment, Drug Resist. Updat, doi:10.1016/j.drup.2021.100794
Fu, Cheng, Wu, Understanding SARS-CoV-2-mediated inflammatory responses: From mechanisms to potential therapeutic tools, Virol Sin, doi:10.1007/s12250-020-00207-4
Ghosh, Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors, Bioorg. Med. Chem. Lett, doi:10.1016/j.bmcl.2007.08.031
Giamarellos-Bourboulis, Complex immune dysregulation in COVID-19 patients with severe respiratory failure, Cell Host Microbe, doi:10.1016/j.chom.2020.04.009
Gong, Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19: A retrospective study, BMC Infect. Dis, doi:10.1186/s12879-020-05681-5
He, Peng, Tao, Peng, Yang, Peroxiredoxin-1 aggravates lipopolysaccharide-induced septic shock via promoting inflammation, Biochem. Biophys. Res. Commun, doi:10.1016/j.bbrc.2020.04.149
Hu, Jolkkonen, Zhao, Neurotropism of SARS-CoV-2 and its neuropathological alterations: Similarities with other coronaviruses, Neurosci. Biobehav. Rev, doi:10.1016/j.neubiorev.2020.10.012
Huang, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet, doi:10.1016/s0140-6736(20)30183-5
Huang, Traditional Chinese Medicine (TCM) in the treatment of COVID-19 and other viral infections: Efficacies and mechanisms, Pharmacol. Ther, doi:10.1016/j.pharmthera.2021.107843
Indalao, Sawabuchi, Takahashi, Kido, IL-1β is a key cytokine that induces trypsin upregulation in the influenza virus-cytokine-trypsin cycle, Arch. Virol, doi:10.1007/s00705-016-3093-3
Kuba, Yamaguchi, Penninger, Angiotensin-converting enzyme 2 (ACE2) in the pathogenesis of ARDS in COVID-19, Front. Immunol, doi:10.3389/fimmu.2021.732690
Kung, Molecular virology of SARS-CoV-2 and related coronaviruses, Microbiol. Mol. Biol. Rev, doi:10.1128/mmbr.00026-21
Lamers, Haagmans, SARS-CoV-2 pathogenesis, Nat. Rev. Microbiol, doi:10.1038/s41579-022-00713-0
Lenz, Long-term effects of COVID-19: A review of current perspectives and mechanistic insights, Crit. Rev. Microbiol, doi:10.1080/1040841x.2023.2190405
Liu, Efficacy and safety of integrated traditional chinese and western medicine for corona virus disease 2019 (COVID-19): A systematic review and meta-analysis, Pharmacol. Res, doi:10.1016/j.phrs.2020.104896
Liu, Zhang, He, Li, Chinese herbs combined with Western medicine for severe acute respiratory syndrome (SARS), Cochrane Database Syst. Rev, doi:10.1002/14651858.CD004882.pub3
Oh, Sahota, Mohammadi, Pradhan, Koola, COVID-19 and catatonia: Prevalence, challenges, pathophysiology, and treatment, Ann. Clin. Psychiatry, doi:10.12788/acp.0109
Rose-John, Winthrop, Calabrese, The role of IL-6 in host defence against infections: Immunobiology and clinical implications, Nat. Rev. Rheumatol, doi:10.1038/nrrheum.2017.83
Sa-Ngiamsuntorn, Anti-SARS-CoV-2 activity of andrographis paniculata extract and its major component andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives, J. Nat. Prod, doi:10.1021/acs.jnatprod.0c01324
Samavati, Uhal, ACE2, much more than just a receptor for SARS-COV-2, Front. Cell Infect. Microbiol, doi:10.3389/fcimb.2020.00317
Schaub, Expression and characterization of SARS-CoV-2 spike proteins, Nat. Protoc, doi:10.1038/s41596-021-00623-0
Sharma, Ahmad Farouk, Lal, A review on the novel coronavirus disease evolution, transmission, detection, control and prevention, doi:10.3390/v13020202
Songvut, Suriyo, Panomvana, Rangkadilok, Satayavivad, A comprehensive review on disposition kinetics and dosage of oral administration of Andrographis paniculata, an alternative herbal medicine, in co-treatment of coronavirus disease, Front. Pharmacol, doi:10.3389/fphar.2022.952660
Synowiec, Szczepański, Barreto-Duran, Lie, Pyrc, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A systemic infection, Clin. Microbiol. Rev, doi:10.1128/cmr.00133-20
V'kovski, Kratzel, Steiner, Stalder, Thiel, Coronavirus biology and replication: Implications for SARS-CoV-2, Nat. Rev. Microbiol, doi:10.1038/s41579-020-00468-6
Yamane, Diisopropylamine dichloroacetate, a novel pyruvate dehydrogenase kinase 4 inhibitor, as a potential therapeutic agent for metabolic disorders and multiorgan failure in severe influenza, PLoS ONE, doi:10.1371/journal.pone.0098032
Yang, Islam, Wang, Li, Chen, Traditional Chinese Medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): A review and perspective, Int. J. Biol. Sci, doi:10.7150/ijbs.45538
Yang, Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection, Comp. Med
You, Inspiration for COVID-19 treatment: Network analysis and experimental validation of baicalin for cytokine storm, Front. Pharmacol, doi:10.3389/fphar.2022.853496
Zandi, Baicalein and Baicalin Inhibit SARS-CoV-2 RNA-Dependent-RNA Polymerase, Microorganisms, doi:10.3390/microorganisms9050893
Zhang, Penninger, Li, Zhong, Slutsky, Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: Molecular mechanisms and potential therapeutic target, Intensive Care Med, doi:10.1007/s00134-020-05985-9
Zhao, Suppressive effects of sunitinib on a TLR activation-induced cytokine storm, Eur. J. Pharmacol, doi:10.1016/j.ejphar.2019.04.045
Zhao, Systems pharmacological study illustrates the immune regulation, anti-infection, anti-inflammation, and multi-organ protection mechanism of Qing-Fei-Pai-Du decoction in the treatment of COVID-19, Scientific Reports, doi:10.1016/j.phymed.2020.153315
Zhu, Hou, Yang, Network pharmacology integrated with experimental validation revealed the anti-inflammatory effects of Andrographis paniculata, Sci. Rep, doi:10.1038/s41598-021-89257-6
Zumla, Chan, Azhar, Hui, Yuen, Coronaviruses-Drug discovery and therapeutic options, Nat. Rev. Drug Discov, doi:10.1038/nrd.2015.37
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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