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    Review of '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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    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 ApproachCrossref
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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

    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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      Review information

      10.14293/S2199-1006.1.SOR-MED.APDSL3Y.v1.RGZTBB
      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.

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

      Review text

      This article emphasizes the need for further research on (phyto)molecules that could be used for the prevention and treatment of COVID-19. Frist step, provided in this article, is molecular docking. Molecules that are proved to be relevant by moleculart docking methods must be further investigated in preclinical and clinical studies. Authors provided an in silico evidence that phenformin and Docosahexaenoic acid (DHA) are potent ACE2 and IL-6 inhibitors, and it could be used to block the SARS-CoV-2 entry in the human respiratory cells, but more preclinical and clinical research is mandatory. DHA is a potent antioxidant and it could be useful in lowering the risk for cytokine storm. Authors also emphasize the important of cytokine storm in COVID-19 pathophysiology. The more severe cytokine storm is, the more sever is the disease. Cytokine storm is associated with poor clinical outcomes and therefore, the investigation of molecules that could prevent cytokine storm or lower its intensitiy is very important.

      Comments

      I apologize for the typo and I will correct it here: ´the importance´ of cytokine storm.

      2021-10-02 07:53 UTC
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