Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway

Zika virus (ZIKV) is an emerging mosquito-borne pathogen associated with microcephaly and other congenital abnormalities in newborns as well as neurologic complications in adults. The explosive transmission of the virus in the last ten years put it in the limelight and improved our understanding of its biology and pathology. Currently, no vaccine or drugs are available to prevent or treat ZIKV infections. Knowing the potential of flaviviruses to broaden their geographic distribution, as observed for the West Nile virus, it is of importance to develop novel antiviral strategies. In this work, we identified poly(sodium 4-styrenesulfonate) (PSSNa) as a new polymeric ZIKV inhibitor. We demonstrated that PSSNa inhibits ZIKV replication in vitro both in animal and human cells, while no cytotoxicity is observed. Our mechanistic studies indicated that PSSNa acts mostly through direct binding to ZIKV particle and blocking its attachment to the host cells.

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“…To determine at which step PSSNa hampers the ZIKV replication, a set of mechanistic assays was performed as described before [ 37 ].…”

Section: Methodsmentioning

confidence: 99%

“…To determine at which step PSSNa hampers the ZIKV replication, a set of mechanistic assays was performed as described before [37]. Assay I, "Virus inactivation assay", verified the direct inactivation of the virus by the tested compound.…”

Section: Mechanism Of Action Assaysmentioning

confidence: 99%

In Vitro Inhibition of Zika Virus Replication with Poly(Sodium 4-Styrenesulfonate)

Botwina

Obłoza

Szczepański

et al. 2020

Viruses

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“…101 Downregulated expression of MAPKs was detected in recovered COVID-19 patients, indicating the MAPK signal pathway may be one sign of patient recovery. 136 Berberine has been found to hamper influenza A and enterovirus 71 replication through inhibition of MAPK/ERK signaling pathway, 137,138 thus, inhibition of the ERK signaling pathway is one of the primary potential mechanisms of action for berberine suppression of SARS-CoV and SARS-CoV-2 replication. 139 Apoptosis-related genes including CASP3, CASP8, BAX, BID, BCL2, and BCL2L1 can initiate apoptotic signaling (P5) via the extrinsic pathway or intrinsic pathway.…”

Section: Pathway Analysis Reveals Complex Signal Transduction Regulmentioning

confidence: 99%

A small molecule compound berberine as an orally active therapeutic candidate against COVID‐19 and SARS: A computational and mechanistic study

Wang

Maskey

et al. 2021

The FASEB Journal

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The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug-and infectioninduced liver injury, as well as reducing oxidative stress. In particular, berberine has a wide range of antiviral activities such as anti-influenza, anti-hepatitis C, anticytomegalovirus, and anti-alphavirus. As an ingredient recommended in guidelines issued by the China National Health Commission for COVID-19 to be combined with other therapy, berberine is a promising orally administered therapeutic candidate against SARS-CoV and SARS-CoV-2. The current study comprehensively evaluates the potential therapeutic mechanisms of berberine in preventing and treating COVID-19 and SARS using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analysis, and 2 of 19 | WANG et Al. 1 | INTRODUCTION Coronavirus disease-19 (COVID-19) is an infectious disease caused by a newly discovered coronavirus SARS-CoV2 that has reached global pandemic status and become a major global health threat. As of December 1 2020, there have been 63,751,931 confirmed cases and 1,477,976 deaths worldwide. 1 The United States hit record-high daily COVID-19 cases in November, 2020. Since the pandemic started in March, 2020, the nation has surpassed 12 million cases and more than 266,000 Americans have died. United States could see "a surge upon a surge" of COVID-19 cases this winter. 2 During just two full days at the end of November, 2020, the country saw over 360,000 new COVID-19 cases nationwide, in addition to over 2,700 new deaths. In 2003, a zoonotic coronavirus outbreak of SARS-CoV had resulted in severe SARS with fatality rates of 10%. 3-6 The SARS-CoV-2 genome shares approximately 70%-80% sequence similarity to SARS-CoV, and causes similar clinical symptoms. 7,8 Key clinical features of COVID-19 and SARS include fever, chills, muscle pain, headache, sore throat, new loss of taste or smell, cough, shortness of breath, gastrointestinal problems in mild to moderate cases, and more serious disease involving pneumonia, acute respiratory distress syndrome, cardiovascular and hepatic failure with high morbidity. 7,8 Individuals with pre-existing conditions like cardiovascular disease, hypertension, asthma, and diabetes, 9 and elderly patients are at a higher risk to become infected with severe symptoms. 10 To date, no specific therapeutic drug or vaccine COVID-19 and SARS is available, resulting in an urgent need for broad-spectrum therapeutics for COVID-19 and other CoV infections.

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“…Mutation of Raf and ERK or treatment with MEK inhibitor (U0126) could signi cantly inhibit virus propagation [31,32] . Berberine is a major component of a variety of traditional Chinese medicines, and it can hinder the replication of in uenza A by inhibiting the nucleolar export of viral ribonucleoproteins mediated by the ERK pathway in vitro [33] .…”

Section: Discussionmentioning

confidence: 99%

Prediction of the mechanisms of action of Yinqiao powder in Influenza: A network pharmacology study

shen

Fan

2020

Preprint

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Objective To predict the potential target and pharmacological mechanism of Yinqiao Powder (YQP) in the treatment of influenza. MethodsThe symptom mapping (SymMap) platform was retrieved to obtain the targets of all herbs in YQP. Influenza-related targets were obtained using the Comparative Toxicogenomics Database (CTD) and DisgeNet database. The String database was used to construct the protein-protein interaction (PPI) network; the Metascape platform was used to enrich key targets by GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Data were visualized and analyzed using software such as Bioinformatics, Edrawmax, and Cytoscape. Results A total of 263 potential targets of YQP for influenza treatment were screened. There are 256 nodes and 3697 edges in the PPI network. The key targets of the PPI network are AKT1, TP53, INS, IL6, MAPK3, VEGFA, etc. The results of Go enrichment showed that YQP can interfere with biological processes such as response to toxic substance, cytokine-mediated signaling pathway, response to lipopolysaccharide, response to extracellular stimulus, and positive regulation of cell death. The results of KEGG pathway enrichment showed that YQP could interfere with the infection process of the influenza virus by intervening PI3K/Akt, TNF, IL-17, MAPK, and other pathways. Conclusion This study reflects the multi-target and multi-pathway action characteristics of Yinqiaosan, and its mechanism of action in the treatment of influenza may be related to the regulation of PI3K-Akt, NF-kappa B, and MAPK signaling pathways. However, further experimental studies are needed to verify the specific mechanism of YQP.

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Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway

Cited by 26 publications

References 43 publications

In Vitro Inhibition of Zika Virus Replication with Poly(Sodium 4-Styrenesulfonate)

In Vitro Inhibition of Zika Virus Replication with Poly(Sodium 4-Styrenesulfonate)

A small molecule compound berberine as an orally active therapeutic candidate against COVID‐19 and SARS: A computational and mechanistic study

Prediction of the mechanisms of action of Yinqiao powder in Influenza: A network pharmacology study

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