Comprehensive assessment of side effects in COVID-19 drug pipeline from a network perspective

Wu, Qihui; Fan, Xiude; Hong, Honghai; Gu, Yong; Liu, Zhihong; Fang, Shuhuan; Wang, Qi; Fang, Jiansong

doi:10.1016/j.fct.2020.111767

Cited by 15 publications

(10 citation statements)

References 51 publications

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“…It is widely recognized that drug-likeness evaluation and ADMET screening are the essential steps in the early stage of drug development that help to avoid late-stage failures [ 43 , 44 ]. Thus, before the wet-lab experiments, a comprehensive in silico evaluation was conducted on the 10 predicted antiphotoaging ginsenosides.…”

Section: Resultsmentioning

confidence: 99%

Chemical Distance Measurement and System Pharmacology Approach Uncover the Novel Protective Effects of Biotransformed Ginsenoside C-Mc against UVB-Irradiated Photoaging

Liu

Hwang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Long-term exposure to ultraviolet light induces photoaging and may eventually increase the risk of skin carcinogenesis. Rare minor ginsenosides isolating from traditional medicine Panax (ginseng) have shown biomedical efficacy as antioxidation and antiphotodamage agents. However, due to the difficulty of component extraction and wide variety of ginsenoside, the identification of active antiphotoaging ginsenoside remains a huge challenge. In this study, we proposed a novel in silico approach to identify potential compound against photoaging from 82 ginsenosides. Specifically, we calculated the shortest distance between unknown and known antiphotoaging ginsenoside set in the chemical space and applied chemical structure similarity assessment, drug-likeness screening, and ADMET evaluation for the candidates. We highlighted three rare minor ginsenosides (C-Mc, Mx, and F2) that possess high potential as antiphotoaging agents. Among them, C-Mc deriving from American ginseng (Panax quinquefolius L.) was validated by wet-lab experimental assays and showed significant antioxidant and cytoprotective activity against UVB-induced photodamage in human dermal fibroblasts. Furthermore, system pharmacology analysis was conducted to explore the therapeutic targets and molecular mechanisms through integrating global drug-target network, high quality photoaging-related gene profile from multiomics data, and skin tissue-specific expression protein network. In combination with in vitro assays, we found that C-Mc suppressed MMP production through regulating the MAPK/AP-1/NF-κB pathway and expedited collagen synthesis via the TGF-β/Smad pathway, as well as enhanced the expression of Nrf2/ARE to hold a balance of endogenous oxidation. Overall, this study offers an effective drug discovery framework combining in silico prediction and in vitro validation, uncovering that ginsenoside C-Mc has potential antiphotoaging properties and might be a novel natural agent for use in oral drug, skincare products, or functional food.

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Section: Resultsmentioning

confidence: 99%

Chemical Distance Measurement and System Pharmacology Approach Uncover the Novel Protective Effects of Biotransformed Ginsenoside C-Mc against UVB-Irradiated Photoaging

Liu

Hwang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Drug-induced side effects are also being assessed in the current network-based framework of COVID-19 studies [ 33 ]. Resources for drug side effects such as SIDER, DrugMatrix, DPIS are listed in the OverCOVID web portal.…”

Section: Resultsmentioning

confidence: 99%

OverCOVID: an integrative web portal for SARS-CoV-2 bioinformatics resources

Ahsan

Liu

Cong

et al. 2021

Journal of Integrative Bioinformatics

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Outbreaks of COVID-19 caused by the novel coronavirus SARS-CoV-2 is still a threat to global human health. In order to understand the biology of SARS-CoV-2 and developing drug against COVID-19, a vast amount of genomic, proteomic, interatomic, and clinical data is being generated, and the bioinformatics researchers produced databases, webservers and tools to gather those publicly available data and provide an opportunity of analyzing such data. However, these bioinformatics resources are scattered and researchers need to find them from different resources discretely. To facilitate researchers in finding the resources in one frame, we have developed an integrated web portal called OverCOVID (http://bis.zju.edu.cn/overcovid/). The publicly available webservers, databases and tools associated with SARS-CoV-2 have been incorporated in the resource page. In addition, a network view of the resources is provided to display the scope of the research. Other information like SARS-CoV-2 strains is visualized and various layers of interaction resources is listed in distinct pages of the web portal. As an integrative web portal, the OverCOVID will help the scientist to search the resources and accelerate the clinical research of SARS-CoV-2.

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“…The mean and standard deviation of the reference distribution were used to calculate a z-score by normalizing the observed (non-Euclidean) distance. More information on the network proximity measure is presented in earlier studies (Fang et al, 2022;Wu et al, 2020).…”

Section: Network Proximity Analysismentioning

confidence: 99%

Endophenotype Network-based Approach reveals the Pharmacological Mechanism of Osthole against D-Galactose Induced Cognitive Disorder in Rats

Wang

Lai

et al. 2023

Preprint

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Background: Osthole, a natural coumarin, found in many medicinal plants. Previous studies have shown its neuroprotective effects, whereas the effect and fundamental mechanism of Osthole for alleviating AD-associated dysmnesia is still not fully clear. Purpose: This study aimed to examine the neuroprotection of Osthole against cognitive impairment in the D-galactose-induced rats and its pharmacological mechanism. Method: The rat was constructed by subcutaneous injection of D-galactose at a dose of 150 mg/kg/day for 56 days as a model. The effect of Osthole on cognitive impairment was evaluated by behavior and biochemical analysis. Subsequently, a combination of in silico prediction and experimental validation was performed to determine the underlying mechanisms of Osthole against Alzheimer's disease, while to verify the network-based predictions, western blot, Nissl staining, and immunofluorescence were applied. Result: Osthole could improve memory dysfunction induced by D-galactose in Sprague Dawley male rat. Endophenotype-based network approach highlight several AD-related pathological processes that may be regulated by Osthole, including neuronal apoptosis, neuroinflammationand endoplasmic reticulum stress. Among them, the proapoptotic markers (Bax), antiapoptotic protein (Bcl-2), moreover, the microgliosis (Iba-1), Astrocytosis (GFAP), and inflammatory cytokines (TNF-α1), levels of ER stress-associated proteins (BIP, p-PERK/PERK, Caspase12, CHOP and XBP1s) were evaluated in both hippocampus and cortex. And the results indicated that Osthole significantly ameliorated neuronal apoptosis, neuroinflammation and ER stress in D-galactose induced rats. Conclusion: This study explored the pharmacological mechanism of Osthole against D-galactose induced memory impairment and identified Osthole as a potential anti-AD drug candidate targeting multiple signaling pathways by endophenotype network-based.

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Comprehensive assessment of side effects in COVID-19 drug pipeline from a network perspective

Cited by 15 publications

References 51 publications

Chemical Distance Measurement and System Pharmacology Approach Uncover the Novel Protective Effects of Biotransformed Ginsenoside C-Mc against UVB-Irradiated Photoaging

Chemical Distance Measurement and System Pharmacology Approach Uncover the Novel Protective Effects of Biotransformed Ginsenoside C-Mc against UVB-Irradiated Photoaging

OverCOVID: an integrative web portal for SARS-CoV-2 bioinformatics resources

Endophenotype Network-based Approach reveals the Pharmacological Mechanism of Osthole against D-Galactose Induced Cognitive Disorder in Rats

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