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HGNC Genes

SARS-CoV-2 proteins

NSP5 (4)

NSP3 (1)


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    SARS-CoV-2 Nsp5 HGNC Protein Causes Acute Lung Inflammation MESHD: A Dynamical Mathematical Model

    Authors: José Díaz; Elena R. Álvarez-Buylla; Antonio Bensussen

    id:10.20944/preprints202012.0749.v2 Date: 2021-03-15 Source: Preprints.org

    In the present work we propose a dynamical mathematical model of the lung cells inflammation process MESHD in response to SARS-CoV-2 infection MESHD. In this scenario the main protease PROTEIN Nsp5 HGNC enhances the inflammatory process, increasing the levels of NF kB, IL-6 HGNC, Cox2 HGNC, and PGE2 with respect to a reference state without the virus. In presence of the virus the translation rates of NF kB and IkB arise to a high constant value, and when the translation rate of IL-6 HGNC also increases above the threshold value of 7 pg mL-1 s-1 the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6 HGNC. Our model shows how such over stimulated immune state becomes autonomous of the signals from other immune cells such as macrophages and lymphocytes, and does not shut down by itself. We also show that in the context of the dynamical model presented here, Dexamethasone or Nimesulide have little effect on such inflammation MESHD state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5 HGNC.To that end, our model suggest that drugs like Saquinavir may be useful. In this form, our model suggests that Nsp5 HGNC is effectively a central node underlying the severe acute lung inflammation MESHD during SARS-CoV-2 infection MESHD. The persistent production of IL-6 HGNC by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19 MESHD. Nsp5 HGNC seems to be the switch to start inflammation MESHD, the consequent overproduction of the ACE2 HGNC receptor, and an important underlying cause of the most severe cases of COVID19 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.

    SARS-CoV-2 proteases cleave IRF3 HGNC and critical modulators of inflammatory pathways ( NLRP12 HGNC and TAB1): implications for disease presentation across species and the search for reservoir hosts.

    Authors: Mehdi Moustaqil; Emma Ollivier; Hsin-Ping Chiu; Paulina Rudolffi-Soto; Sarah Van Tol; Christian Stevens; Akshay Bhumkar; Dominic J.B. Hunter; Alexander N. Freiberg; David Jacques; Benhur Lee; Emma Sierecki; Yann Gambin

    doi:10.1101/2020.06.05.135699 Date: 2020-06-05 Source: bioRxiv

    The genome of SARS-CoV-2 ( SARS2 MESHD) encodes for two viral proteases ( NSP3 PROTEIN NSP3 HGNC/ papain-like protease PROTEIN and NSP5 HGNC NSP5 PROTEIN/ 3C-like protease or major protease) that are responsible for cleaving viral polyproteins for successful replication. NSP3 PROTEIN NSP3 HGNC and NSP5 HGNC NSP5 PROTEIN of SARS-CoV (SARS1) are known interferon antagonists. Here, we examined whether the protease function of SARS2 MESHD NSP3 HGNC NSP3 PROTEIN and NSP5 PROTEIN NSP5 HGNC target proteins involved in the host innate immune response. We designed a fluorescent based cleavage assay to rapidly screen the protease activity of NSP3 PROTEIN NSP3 HGNC and NSP5 PROTEIN NSP5 HGNC on a library of 71 human innate immune proteins (HIIPs), covering most pathways involved in human innate immunity. By expressing each of these HIIPs with a genetically encoded fluorophore in a cell-free system and titrating in the recombinant protease domain of NSP3 HGNC NSP3 PROTEIN or NSP5 PROTEIN NSP5 HGNC, we could readily detect cleavage of cognate HIIPs on SDS-page gels. We identified 3 proteins that were specifically and selectively cleaved by NSP3 PROTEIN NSP3 HGNC or NSP5 HGNC NSP5 PROTEIN: IRF-3 HGNC, and NLRP12 HGNC and TAB1, respectively. Direct cleavage of IRF3 HGNC by NSP3 HGNC NSP3 PROTEIN could explain the blunted Type- I IFN response seen during SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHDs while NSP5 PROTEIN NSP5 HGNC mediated cleavage of NLRP12 HGNC and TAB1 point to a molecular mechanism for enhanced production of IL-6 HGNC and inflammatory response observed in COVID-19 MESHD patients. Surprisingly, both NLRP12 HGNC and TAB1 have each two distinct cleavage sites. We demonstrate that in mice, the second cleavage site of NLRP12 is absent. We pushed this comparative alignment of IRF-3 and NLRP12 homologs and show that the lack or presence of cognate cleavage motifs in IRF-3 and NLRP12 could contribute to the presentation of disease in cats and tigers, for example. Our findings provide an explanatory framework for in-depth studies into the pathophysiology of COVID-19 MESHD and should facilitate the search or development of more effective animal models for severe COVID-19 MESHD. Finally, we discovered that one particular species of bats, Davids Myotis, possesses the five cleavage sites found in humans for NLRP12 HGNC, TAB1 and IRF3 HGNC. These bats are endemic from the Hubei province in China and we discuss its potential role as reservoir for the evolution of SARS1 and SASR2.

    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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