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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

NSP5 (4)

ProteinS (2)

NSP2 (1)


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    Chemical composition and pharmacological mechanism of Ephedra-Glycyrrhiza drug pair  against coronavirus disease 2019 MESHD ( COVID-19 MESHD)

    Authors: Qin Qiu; Mingyue Li; Haowen Lin; Shilin Cao; Qu Wang; Xiaoling Li; Zishi Chen; Wenhao Jiang; Yuge Huang; Hui Luo; lianxiang luo

    doi:10.21203/rs.3.rs-46829/v1 Date: 2020-07-21 Source: ResearchSquare

    Background:  Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is currently spreading all over the world, and the prospect of a very rapid increase in COVID-19 MESHD cases prompted us to seek effective antiviral therapeutics, from the identification of possible drugs to their potential mechanisms. Purpose: The aim of this study was to explore the efficacy of the Ephedra-Glycyrrhiza (EG) drug pair on coronavirus disease 2019 MESHD ( COVID-19 MESHD) by network pharmacology and molecular docking. Methods: The main active compounds, target information, meridians and properties of EG were obtained through the TCMSP and ETCM databases. The targeted information of COVID-19 MESHD was acquired from the GeneCards database. EG drug pair applied diseases were analysed by DAVID and the drug-bank database, and visualized by Rstudio and Cytoscape 3.7.2. Then, we carried out targeted intersection of the EG drug pair and COVID-19 MESHD to map the compound-target-disease interactions and visualize them with Cytoscape 3.7.2 and Venny 2.1. In addition, the enrichment analysis of the GO and KEGG pathways were visualized with Rstudio and PathVisio software through the DAVID database. Finally, we carried out the molecular docking of the EG active compounds with M hydrolase ( Mpro PROTEIN), spike protein (S PROTEIN S protein HGNC) and angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC), and the binding modes between GE and the protein were verified via molecular dynamics (MD) simulation. Results: We identified 112 active EG compounds by network pharmacological analysis. Drug pair enrichment analysis demonstrated that these compounds may participate in the cAMP, PI3K-Akt, JAK-STAT and chemokine signalling pathways, which had a high correlation with respiratory system, nervous system, blood circulation system and digestive system related diseases. Pathway analysis between EG and COVID-19 MESHD showed that the key targets were TNF HGNC, IL2 HGNC, FOS HGNC, ALB HGNC and PTGS2 HGNC. They may regulate the PI3K-Akt signalling pathway and natural killer cell-mediated cytotoxicity MESHD to play roles in immune regulation, organ protection, antiviral, immune regulation, and organ protection as well as having antiviral effects. Molecular docking results showed that the active EG compounds bind well to Mpro PROTEIN, S protein HGNC S protein PROTEIN and ACE2 HGNC. The binding modes between the active compounds of the EG and protein were verified via MD simulation. Conclusion: The EG drug pair can treat COVID-19 MESHD through multiple targets and pathways, which can provide a theoretical basis for further study of the mechanism of action of the EG drug pair on COVID-19 MESHD.

    The Important Herbal Pair for the Treatment of COVID-19 MESHD and Its Possible Mechanisms

    Authors: Shujie Xia; Zhangfeng Zhong; Bizhen Gao; Chi Teng Vong; Xuejuan Lin; Jin Cai; Hanlu Gao; Ging Chan; CanDong Li

    doi:10.21203/rs.3.rs-46828/v4 Date: 2020-07-21 Source: ResearchSquare

    Background: Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) is an unprecedented disaster for people around the world. Many studies have shown that traditional Chinese medicine (TCM) are effective in treating COVID-19 MESHD. However, it is difficult to find the most effective combination herbal pair among numerous herbs, as well as identifying its potential mechanisms. Herbal pair is the main form of a combination of TCM herbs, which is widely used for the treatment of diseases. It can also help us to better understand the compatibility of TCM prescriptions, thus improving the curative effects. The purpose of this article is to explore the compatibility of TCM prescriptions and identify the most important herbal pair for the treatment of COVID-19 MESHD, and then analyze the active components and potential mechanisms of this herbal pair. Methods: We first systematically sorted the TCM prescriptions recommended by the leading experts for treating COVID-19 MESHD, and the specific herbs contained in these prescriptions across different stages of the disease. Next, the association rule approach was employed to examine the distribution and compatibility among these TCM prescriptions, and then identify the most important herbal pair. On this basis, we further investigated the active ingredients and potential targets in the selected herbal pair by a network pharmacology approach, and analyzed the potential mechanisms against COVID-19 MESHD. Finally, the main active compounds in AE were selected for molecular docking with severe acute respiratory syndrome coronavirus 2 MESHD (SARS-COV-2) 3CLpro PROTEIN and angiotensin converting enzyme II (ACE2) for further verification. Result: We obtained 32 association rules for the herbal combinations in the selection of TCM treatment for COVID-19 MESHD. The results showed that the combination of Amygdalus Communis Vas (ACV) and Ephedra sinica Stapf (ESS) had the highest confidence degree and lift value, as well as high support degree, which can be used in almost all the stages of COVID-19 MESHD, so ACV and ESS (AE) were selected as the most important herbal pair. There were 26 active ingredients and 44 potential targets, which might be related to the herbal pair of AE against COVID-19 MESHD. The main active ingredients of AE against COVID-19 MESHD were quercetin, kaempferol, luteolin, while the potential targets were Interleukin 6 HGNC ( IL-6 HGNC), Mitogen-activated Protein Kinase 1 (MAPK)1 HGNC, MAPK8 HGNC, Interleukin-1β HGNC ( IL-1β HGNC), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 subunit ( RELA HGNC). The protein-protein interaction (PPI) cluster demonstrated that IL-6 HGNC was the seed in the cluster, which plays an important role in connecting other nodes in the PPI network. The potential pathways mainly involved tumor necrosis MESHD factor ( TNF HGNC), Toll-like receptor (TLR), hypoxia MESHD-inducible factor-1 ( HIF-1 HGNC), and nucleotide-binding oligomerization domain (NOD)-like receptor (NLRs). The molecular docking results showed that the main active ingredients of AE had good affinity with SARS-COV-2 3CLpro PROTEIN and ACE2, which was consistent with the above analysis. Conclusion: There were 32 association rules in the TCM prescriptions recommended by experts for COVID-19 MESHD. The combination of ACV and EAS was the most important herbal pair for the treatment of COVID-19 MESHD. AE might have therapeutic effects against COVID-19 MESHD by affecting the inflammatory and immune responses, cell apoptosis, hypoxia damage MESHD and other pathological processes through multiple components, targets and pathways.

    Active-site Molecular docking of Nigellidine to nucleocapsid/ Nsp2 HGNC/ Nsp3 HGNC/MPro of COVID-19 MESHD  and to human IL1R HGNC and TNFR1/2 may stop viral-growth/cytokine-flood, and the drug source Nigella sativa (black cumin) seeds show potent antioxidant role in experimental rats.

    Authors: Smarajit Maiti; Amrita Banerjee; Aarifa Nazmeen; Mehak Kanwar; Shilpa Das

    doi:10.21203/rs.3.rs-26464/v1 Date: 2020-05-02 Source: ResearchSquare

    The recent outbreak of SARS CoV-2 has changed the global scenario of human lives and economy. In this pandemic-outbreak the ratio of infected person is much higher than the death encountered. Most of the dead patients were observed with dysfunction/failure of cardiac and renal systems MESHD. Beside this a ‘cytokine storm’ namely TNF-α HGNC/ IL1 HGNC receptors i.e. TNFR1 HGNC/ TNFR2 HGNC/ IL1R HGNC over-functioning was reported in the infected-persons. Here, nigellidine, an indazole-alkaloid and key-component of Nigella Sativa L. ( NS MESHD); black-cumin-seed, has been analyzed for COVID-19 MESHD different protein and TNFα receptors TNFR1 HGNC/ TNFR2 HGNC and IL1R HGNC inhibition through molecular-docking study and biochemical-study of cumin-seed extract exposure to experimental-rat. The NMR, X-ray-crystallographic or Electron-microscopic structures of COVID-19 MESHD Main-protease PROTEIN(6LU7), Spike-glycoprotein PROTEIN(6vsb), NSP2 HGNC NSP2 PROTEIN(QHD43415_2), N-terminus-protenase (QHD43415_3), Nucleocapsid(QHD43423) and Human IL1R HGNC (1itb), TNFR1 HGNC (1ncf), TNFR2 HGNC (3alq) from PDB MESHD were retrieved/analyzed for receptor-ligand interaction in normal condition. Then those structures were docked with nigellidine using Autodock-software and Patchdock-server. Where nigellidine showed highest binding-energy of -7.61 (kcal/mol) and ligand-efficiency value of (-0.35) forming bonds with amino acids THR943/LYS945/MET1556/ALA1557/PRO1558/ILE1559. Highest ACE-value of -356.72 was also observed for nigellidine N-terminal-protease interaction. Nigellidine also showed strong interaction with NSP2 HGNC NSP2 PROTEIN (-6.28) and Mpro PROTEIN/3CLpro_Q (-6.38s). Nigellidine showed affinity to TNFR1 HGNC (-6.81), IL1R HGNC (-6.23) and TNFR2 HGNC (-5.16). In rat experiment 2-groups (vehicle and NS treated) of female Wistar-rats were taken for experiments. The NS treated tissue showed marked decline in ALP MESHD/SGPT/ SGOT/MDA level then the basal-levels. From the Western-blot or activity analysis it was observed that Nigellidine, the sulfuryl-group containing drug showed no impact on Phenol-catalyzing ASTIV or Steroid-catalyzing EST expressions/activities and thus have no influence in sulfation-mediated adverse metabolic-processes. Current-results concluded that Nigellidine has hepato/reno-protective; immunomodulatory/anti-inflammatory and antioxidant activities as well as it inhibits important proteins of COVID-19 MESHD. With steps to further validation/checking nigellidine can be used in COVID-19 MESHD infection.

    Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production

    Authors: Natalia Fintelman-Rodrigues; Carolina Q Sacramento; Carlyle Ribeiro Lima; Franklin Souza da Silva; Andre Ferreira; Mayara Mattos; Caroline S. de Freitas; Vinicius Cardoso Soares; Suelen da Silva Gomes Dias; Jairo R. Temerozo; Milene Miranda; Aline R. Matos; Fernando A Bozza; Nicolas Carels; Carlos Roberto Alves; Marilda M Siqueira; Patricia T. Bozza; Thiago Moreno L. Souza

    doi:10.1101/2020.04.04.020925 Date: 2020-04-05 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is already responsible for far more deaths than previous pathogenic coronaviruses (CoVs) from 2002 and 2012. The identification of clinically approved drugs to be repurposed to combat 2019 CoV disease MESHD ( COVID-19 MESHD) would allow the rapid implementation of potentially life-saving procedures. The major protease ( Mpro) of SARS-CoV-2 PROTEIN is considered a promising target, based on previous results from related CoVs with lopinavir (LPV), an HIV protease inhibitor. However, limited evidence exists for other clinically approved antiretroviral protease inhibitors, such as atazanavir (ATV). ATV is of high interest because of its bioavailability within the respiratory tract. Our results show that ATV could dock in the active site of SARS-CoV-2 Mpro PROTEIN, with greater strength than LPV. ATV blocked Mpro PROTEIN activity. We confirmed that ATV inhibits SARS-CoV-2 replication, alone or in combination with ritonavir (RTV) in Vero cells, human pulmonary epithelial cell line and primary monocytes, impairing virus-induced enhancement of IL-6 HGNC and TNF HGNC- levels. Together, our data strongly suggest that ATV and ATV/RTV should be considered among the candidate repurposed drugs undergoing clinical trials in the fight against COVID-19 MESHD.

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MeSH Disease
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SARS-CoV-2 Proteins


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