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      Natural phytochemicals, Phenformin, and Docosahexaenoic acid (DHA) as a Novel Inhibitors of IL-6 and ACE2 receptors, a Therapeutic Strategy for targeting COVID-19 Cell Entry and Cytokine Storm. An insilico Approach

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      Ace2, Covid-19, phenoformin, molecular docking, bromealin, EGCG, DHA, interleukin 6, il-6

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          Abstract

          Cytokine storm syndrome (CSS) is a life-threatening consequence of inflammatory immunological illnesses; it can also occur with COVID-19 infection . CSS is characterized by a disruption in cytokine synthesis, including regulatory , pro-inflammatory andanti-inflammatory cytokines, resulting in pathologic stimulation of innate in addition to adaptive (Th17and Th1mediated) response. In the pathophysiology of CSS, interleukin-6 could play a key role. The significant role of IL-6 in COVID-19pathogenesis was established in a wide variety of researches , which reported that the plasma concentration of IL-6was raised in COVID-19 patients with severe symptoms .COVID-19 spike protein binding to angiotensin-converting enzyme 2 (ACE2), the virus's cellular receptor, causes a cascade of molecular processes that could result in hyperinflammation which may lead to cytokine storm . Therefore, the development of new naturaltherapies and repurposing some drugs such as Phenformin and Docosahexaenoic acidthat could compete with COVID-19 for ACE2 binding or inhibit IL-6 activity may possibly help COVID-19 patients avoid a cytokine storm and save their lives through inhibiting IL-6 and preventing SARS-CoV-2 RBD attachment to ACE2. Herein we made a docking based screening for some natural phytochemicals anddrugs that could be repurposed according to our findings to counter COVID-19 cell entry and inhibitthe hyper activation of IL-6. Our results revealed that a five phytochemicalsincluding Epigallocatechin gallate (EGCG) , bromelain, luteolin , vitexin and isovitexin)showed a high binding affinities with best interactions with the active sites of IL-6 .The binding affinities of these phytochemicalsincluding,EGCG , bromelain, luteolin , vitexin and isovitexinwith IL-6 were (-7.7,-6.7, -7.4, -7.2 and -7.3 ), respectively. In addition to ,phenforminshowed a high binding affinity with best interactions with the active sites of IL-6 and ACE2 . The binding affinity of phenformin with IL-6 was (-7.4) and with ACE 2 ( -7.2).Docosahexaenoic acid (DHA) had a moderate binding affinity and moderate interactions with the active sites of IL-6 and had a high binding affinity with best interactions with ACE2 active sites. The binding affinity of Docosahexaenoic acid(DHA)with IL-6 was (-5.3) and with AC2 (-6.3).

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          Author and article information

          Journal
          ScienceOpen Preprints
          ScienceOpen
          20 September 2021
          Affiliations
          [1 ] Director of tuberculosis program Ghubera, public health department ,First health cluster ,Ministry of health , Riyadh, Saudia Arabia.
          [2 ] Department of chemistry and biochemistry, Faculty of Science, Damietta University, Egypt
          Author notes
          Article
          10.14293/S2199-1006.1.SOR-.PPDSL3Y.v1

          This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

          The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

          Medicine, Immunology, Infectious disease & Microbiology

          molecular docking, il-6, EGCG, bromealin, Ace2, interleukin 6, phenoformin, Covid-19, DHA

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