Study of Baicalin toward COVID-19 Treatment: In silico Target Analysis and in vitro Inhibitory Effects on SARS-CoV-2 Proteases

Lin, Chi‐Tsai; Tsai, Fuu‐Jen; Hsu, Yu-Ting; Ho, Tsung‐Jung; Wang, Guo-Kai; Chiu, Yu–Jen; Ha, Hai‐Anh; Yang, Jai Sing

doi:10.1159/000519564

Cited by 26 publications

(18 citation statements)

References 47 publications

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“…Encouragingly, a recent study identified good binding affinity of baicalin to the major targets of SARS-CoV-2, 3-trypsin-like cysteine protease (3CLpro) and papain-like protease (PLpro), using pharmacophore fitting and molecular docking techniques ( Lin et al, 2021 ). It suggested that baicalin may inhibit proteases and reduce CS through inflammation-related pathways.…”

Section: Discussionmentioning

confidence: 99%

Inspiration for COVID-19 Treatment: Network Analysis and Experimental Validation of Baicalin for Cytokine Storm

You

Fan

et al. 2022

Front. Pharmacol.

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Background: Cytokine storm (CS) is a systemic inflammatory syndrome and a major cause of multi-organ failure and even death in COVID-19 patients. With the increasing number of COVID-19 patients, there is an urgent need to develop effective therapeutic strategies for CS. Baicalin is an anti-inflammatory and antiviral traditional Chinese medicine. In the present study, we aimed to evaluate the therapeutic mechanism of baicalin against CS through network analysis and experimental validation, and to detect key targets of CS that may bind closely to baicalin through molecular docking.Method: Access to potential targets of baicalin and CS in public databases. We constructed the protein-protein interaction (PPI) network of baicalin and CS by Cytoscape 9.0 software and performed network topology analysis of the potential targets. Then, the hub target was identified by molecular docking technique and validated in the CS model. Finally, GO and KEGG pathway functional enrichment analysis of common targets were confirmed using R language, and the location of overlapping targets in key pathways was queried via KEGG Mapper.Result: A total of 86 overlapping targets of baicalin and CS were identified, among which MAPK14, IL2, FGF2, CASP3, PTGS2, PIK3CA, EGFR, and TNF were the core targets. Moreover, it was found that baicalin bound most closely to TNF through molecular docking, and demonstrated that baicalin can effectively inhibit the elevation of TNF-α in vitro and in vivo. Furthermore, bioenrichment analysis revealed that the TNF signaling pathway and IL-17 signaling pathway may be potential key pathways for baicalin to treat CS.Conclusion: Based on this study, baicalin was identified as a potential drug for the alleviation of CS, and the possible key targets and pathways of baicalin for the treatment of CS were elucidated to reveal the main pharmacological mechanisms.

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Section: Discussionmentioning

confidence: 99%

Inspiration for COVID-19 Treatment: Network Analysis and Experimental Validation of Baicalin for Cytokine Storm

You

Fan

et al. 2022

Front. Pharmacol.

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“…Moreover, the action mechanisms of reported chemical compounds in ARND combating COVID-19 were diverse. Pathway analysis indicated that baicalin (drug 4) has targets in human cells associated with signals of pro-inflammatory cytokines [ 82 ]. The results of prediction by using the Swiss Target Prediction server disclosed that norwogonin (drug 4) and baicalein displayed binding with a high affinity for enzymes associated with pulmonary damage, such as arachidonate 15-lipoxygenase (ALOX15), cycline dependent kinase 1 (CDK1), lysine-specific demethylase 4D (KDM4D), and xanthine dehydrogenase (XDH) [ 63 ].…”

Section: Resultsmentioning

confidence: 99%

An anti-inflammatory and anti-fibrotic proprietary Chinese medicine nasal spray designated as Allergic Rhinitis Nose Drops (ARND) with potential to prevent SARS-CoV-2 coronavirus infection by targeting RBD (Delta)- angiotensin converting enzyme 2 (ACE2) binding

Yip

Lee

et al. 2022

Chin Med

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Background Since the outbreak of COVID-19 has resulted in over 313,000,000 confirmed cases of infection and over 5,500,000 deaths, substantial research work has been conducted to discover agents/ vaccines against COVID-19. Undesired adverse effects were observed in clinical practice and common vaccines do not protect the nasal tissue. An increasing volume of direct evidence based on clinical studies of traditional Chinese medicines (TCM) in the treatment of COVID-19 has been reported. However, the safe anti-inflammatory and anti-fibrotic proprietary Chinese medicines nasal spray, designated as Allergic Rhinitis Nose Drops (ARND), and its potential of re-purposing for suppressing viral infection via SARS-CoV-2 RBD (Delta)- angiotensin converting enzyme 2 (ACE2) binding have not been elucidated. Purpose To characterize ARND as a potential SARS-CoV-2 entry inhibitor for its possible preventive application in anti-virus hygienic agent. Methods Network pharmacology analysis of ARND was adopted to asacertain gene targets which were commonly affected by COVID-19. The inhibitory effect of ARND on viral infection was determined by an in vitro pseudovirus assay. Furthermore, ARND was confirmed to have a strong binding affinity with ACE2 and SARS-CoV-2 spike-RBD (Delta) by ELISA. Finally, inflammatory and fibrotic cell models were used in conjunction in this study. Results The results suggested ARND not only inhibited pseudovirus infection and undermined the binding affinity between ACE2 and the Spike protein (Delta), but also attenuated the inflammatory response upon infection and may lead to a better prognosis with a lower risk of pulmonary fibrosis. The data in this study also provide a basis for further development of ARND as an antiviral hygienic product and further investigations on ARND in the live virus, in vivo and COVID-19 patients. ARND holds promise for use in the current COVID-19 outbreak as well as in future pandemics. Conclusion ARND could be considered as a safe anti-SARS-CoV-2 agent with potential to prevent SARS-CoV-2 coronavirus infection. Graphical abstract

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“…Quercetin, apigenin, baicalin, luteolin, hesperidin, genistein, proanthocyanidin and eriodictyol have been found to be capable of alleviating oxidative stress in diabetic nephropathy [63]. Incidentally, all the above flavonoid compounds have been reported to bind to SARS-CoV-2 protein components or the receptor hACE2 [54][55][56][64][65][66][67][68][69]. These flavonoids are also antioxidants suggesting a common mode of action in both COVID-19 and diabetes, which in all probability is through reducing oxidative stress.…”

Section: Synergistic Kidney Damage and Morbidity Due To Covid-19 And ...mentioning

confidence: 99%

Does Oxidative Stress Management Help Alleviation of COVID-19 Symptoms in Patients Experiencing Diabetes?

et al. 2022

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Severe acute respiratory syndrome (SARS)-CoV-2 virus causes novel coronavirus disease 2019 (COVID-19) with other comorbidities such as diabetes. Diabetes is the most common cause of diabetic nephropathy, which is attributed to hyperglycemia. COVID-19 produces severe complications in people with diabetes mellitus. This article explains how SARS-CoV-2 causes more significant kidney damage in diabetic patients. Importantly, COVID-19 and diabetes share inflammatory pathways of disease progression. SARS-CoV-2 binding with ACE-2 causes depletion of ACE-2 (angiotensin-converting enzyme 2) from blood vessels, and subsequently, angiotensin-II interacts with angiotensin receptor-1 from vascular membranes that produce NADPH (nicotinamide adenine dinucleotide hydrogen phosphate) oxidase, oxidative stress, and constriction of blood vessels. Since diabetes and COVID-19 can create oxidative stress, we hypothesize that COVID-19 with comorbidities such as diabetes can synergistically increase oxidative stress leading to end-stage renal failure and death. Antioxidants may therefore prevent renal damage-induced death by inhibiting oxidative damage and thus can help protect people from COVID-19 related comorbidities. A few clinical trials indicated how effective the antioxidant therapy is against improving COVID-19 symptoms, based on a limited number of patients who experienced COVID-19. In this review, we tried to understand how effective antioxidants (such as vitamin D and flavonoids) can act as food supplements or therapeutics against COVID-19 with diabetes as comorbidity based on recently available clinical, preclinical, or in silico studies.

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Study of Baicalin toward COVID-19 Treatment: In silico Target Analysis and in vitro Inhibitory Effects on SARS-CoV-2 Proteases

Cited by 26 publications

References 47 publications

Inspiration for COVID-19 Treatment: Network Analysis and Experimental Validation of Baicalin for Cytokine Storm

Inspiration for COVID-19 Treatment: Network Analysis and Experimental Validation of Baicalin for Cytokine Storm

An anti-inflammatory and anti-fibrotic proprietary Chinese medicine nasal spray designated as Allergic Rhinitis Nose Drops (ARND) with potential to prevent SARS-CoV-2 coronavirus infection by targeting RBD (Delta)- angiotensin converting enzyme 2 (ACE2) binding

Does Oxidative Stress Management Help Alleviation of COVID-19 Symptoms in Patients Experiencing Diabetes?

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