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      The role of berberine in Covid-19: potential adjunct therapy

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          Abstract

          Coronavirus disease 2019 (Covid-19) is a global diastrophic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 leads to inflammatory, immunological, and oxidative changes, by which SARS-CoV-2 leads to endothelial dysfunction (ED), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and multi-organ failure (MOF). Despite evidence illustrating that some drugs and vaccines effectively manage and prevent Covid-19, complementary herbal medicines are urgently needed to control this pandemic disease. One of the most used herbal medicines is berberine (BBR), which has anti-inflammatory, antioxidant, antiviral, and immune-regulatory effects; thus, BBR may be a prospective candidate against SARS-CoV-2 infection. This review found that BBR has anti-SARS-CoV-2 effects with mitigation of associated inflammatory changes. BBR also reduces the risk of ALI/ARDS in Covid-19 patients by inhibiting the release of pro-inflammatory cytokines and inflammatory signaling pathways. In conclusion, BBR has potent anti-inflammatory, antioxidant, and antiviral effects. Therefore, it can be utilized as a possible anti-SARS-CoV-2 agent. BBR inhibits the proliferation of SARS-CoV-2 and attenuates the associated inflammatory disorders linked by the activation of inflammatory signaling pathways. Indeed, BBR can alleviate ALI/ARDS in patients with severe Covid-19. In this sense, clinical trials and prospective studies are suggested to illustrate the potential role of BBR in treating Covid-19.

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          NF-κB signaling in inflammation

          The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses. NF-κB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation. In addition, NF-κB plays a critical role in regulating the survival, activation and differentiation of innate immune cells and inflammatory T cells. Consequently, deregulated NF-κB activation contributes to the pathogenic processes of various inflammatory diseases. In this review, we will discuss the activation and function of NF-κB in association with inflammatory diseases and highlight the development of therapeutic strategies based on NF-κB inhibition.
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            Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods

            SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.
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              The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.

              IL-17-producing T lymphocytes have been recently shown to comprise a distinct lineage of proinflammatory T helper cells, termed Th17 cells, that are major contributors to autoimmune disease. We show here that the orphan nuclear receptor RORgammat is the key transcription factor that orchestrates the differentiation of this effector cell lineage. RORgammat induces transcription of the genes encoding IL-17 and the related cytokine IL-17F in naïve CD4(+) T helper cells and is required for their expression in response to IL-6 and TGF-beta, the cytokines known to induce IL-17. Th17 cells are constitutively present throughout the intestinal lamina propria, express RORgammat, and are absent in mice deficient for RORgammat or IL-6. Mice with RORgammat-deficient T cells have attenuated autoimmune disease and lack tissue-infiltrating Th17 cells. Together, these studies suggest that RORgammat is a key regulator of immune homeostasis and highlight its potential as a therapeutic target in inflammatory diseases.
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                Author and article information

                Contributors
                aobabalghith@uqu.edu.sa
                Hayderm36@yahoo.com
                Dr.alialgareeb78@yahoo.com
                michel.dewaard@univ-nantes.fr
                sabatier.jm1@gmail.com
                walaa.negm@pharm.tanta.edu.eg
                gaberbatiha@gmail.com , dr_gaber_batiha@vetmed.dmu.edu.eg
                Journal
                Inflammopharmacology
                Inflammopharmacology
                Inflammopharmacology
                Springer International Publishing (Cham )
                0925-4692
                1568-5608
                2 October 2022
                : 1-14
                Affiliations
                [1 ]GRID grid.412832.e, ISNI 0000 0000 9137 6644, Medical Genetics Department, College of Medicine, , Umm Al-Qura University, ; Mecca, Kingdom of Saudi Arabia
                [2 ]Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq
                [3 ]Smartox Biotechnology, 6 rue des Platanes, 38120 Saint-Egrève, France
                [4 ]GRID grid.462318.a, L’institut du Thorax, INSERM, CNRS, UNIV NANTES, ; 44007 Nantes, France
                [5 ]GRID grid.460782.f, ISNI 0000 0004 4910 6551, LabEx « Ion Channels, Science and Therapeutics», , Université de Nice Sophia-Antipolis, ; 06560 Valbonne, France
                [6 ]GRID grid.464051.2, ISNI 0000 0004 0385 4984, Faculté des sciences médicales et paramédicales, , Aix-Marseille Université, Institut de Neurophysiopathologie (INP), CNRS UMR, 7051, ; 27 Bd Jean Moulin, 13005 Marseille, France
                [7 ]GRID grid.412258.8, ISNI 0000 0000 9477 7793, Department of Pharmacognosy, Faculty of Pharmacy, , Tanta University, ; Tanta, 31527 Egypt
                [8 ]GRID grid.449014.c, ISNI 0000 0004 0583 5330, Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, , Damanhour University, ; Damanhour, 22511 Al Beheira Egypt
                Author information
                http://orcid.org/0000-0003-0463-8047
                http://orcid.org/0000-0002-7817-425X
                Article
                1080
                10.1007/s10787-022-01080-1
                9526677
                36183284
                ba6e992c-da16-4577-b693-c5d722d64676
                © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 9 August 2022
                : 9 September 2022
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                covid-19,inflammatory signaling pathways,anti-inflammatory,antioxidant,antiviral,immune-regulatory effects

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