ncovitems

results:

Could glutathione depletion be the Trojan horse of COVID-19 mortality?

"This review identified this common pathway to be a low baseline of reduced glutathione (i.e., GSH) level. In particular, this review provided an in-depth discussion regarding the pathophysiology by which COVID-19 leads to GSH depletion, tissue damage, and acute respiratory distress syndrome. In addition, the current review demonstrated how GSH depletion could result in failure of the immune system and rendering the end organs vulnerable to damage from the oxidative stress. CONCLUSIONS: This preclinical study shows that GSH depletion may have a central role in COVID-19 mortality and pathophysiology. Therefore, elevating the GSH level in tissues may decrease the severity and mortality rates of COVID-19."

Molecular modelling of the antiviral action of Resveratrol derivatives against the activity of two novel SARS CoV-2 and 2019-nCoV receptors

"The molecular docking approach can provide a fast prediction of the positive influence the targets on the COVID-19 outbreak. In this work, we choose resveratrol (RV) derivatives (22 cases) and two newly released coordinate structures for COVID-19 as receptors [Papain-like Protease of SARS CoV-2 (PBD ID: 6W9C) and 2019-nCoV RNA-dependent RNA Polymerase (PBD ID: 6M71)]. The results show that conformational isomerism is significant and useful parameter for docking results. A wide spectrum of interactions such as Van der Waals, conventional hydrogen bond, Pi-donor hydrogen bond, Pi-Cation, Pi-sigma, Pi-Pi stacked, Amide-Pi stacked and Pi-Alkyl is detected via docking of RV derivatives and COVID-19 receptors. The potential inhibition effect of RV-13 (-184.99 kj/mol), and RV-12 (-173.76 kj/mol) is achieved at maximum value for 6W9C and 6M71, respectively." A. Ranjbar, M. Jamshidi, S. Torabi Molecular modelling of the antiviral action of Resveratrol derivatives against the activity of two novel SARS CoV-2 and 2019-nCoV receptors Eur Rev Med Pharmacol Sci Year: 2020 Vol. 24 - N. 14 Pages: 7834-7844 DOI: 10.26355/eurrev_202007_22288

Expression of ACE2 and a viral virulence-regulating factor CCN family member 1 in human iPSC-derived neural cells: implications for COVID-19-related CNS disorders

It has been reported that coronavirus disease 2019 (COVID-19) causes not only pneumonia but also systemic inflammations including central nervous system (CNS) disorders. However, little is known about the mechanism that triggers the COVID-19-associated CNS disorders, due to the lack of appropriate experimental systems. Our present study showed that angiotensin-converting enzyme-2 (ACE2), a cellular receptor for SARS-CoV-2, is expressed in human induced pluripotent stem cell (iPSC)-derived neural stem/progenitor cells (hiPSC-NS/PCs) and young neurons. Furthermore, together with database analysis, we found that a viral virulent factor CCN family member 1 (CCN1), which is known to be induced by SARS-CoV-2 infection, is expressed in these cells at basal levels. Considering the role of CCN1 which is known to be involved in viral toxicity and inflammation, hiPSC-NS/PCs could provide an excellent model for COVID-19-associated CNS disorders from the aspect of SARS-CoV-2 infection-ACE2-CCN1 axis. In addition, we identified compounds that reduce CCN1 expression. Collectively, our study using hiPSC-NS/PCs may aid in the development of a therapeutic target for COVID-19-related CNS disorders.

Integrated Bioinformatics Analysis for the Screening of Associated Pathways and Therapeutic Drugs in Coronavirus Disease 2019

COVID-19 caused by a novel coronavirus, a severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has recently broken out worldwide. Up to now, the development of vaccine is still in the stage of clinical research, and there is no clinically approved specific antiviral drug for human coronavirus infection. The purpose of this study is to investigate the key molecules involved in response during SARS-CoV-2 infection and provide references for the treatment of SARS-CoV-2. Methods: We conducted in-depth and comprehensive bioinformatics analysis of human proteins identified with SARS-CoV-2, including functional enrichment analysis, protein interaction network analysis, screening of hub genes, and evaluation of their potential as therapeutic targets. In addition, we used the gene-drug database to search for inhibitors of related biological targets. Results: Several significant pathways, such as PKA, centrosome and transcriptional regulation, may greatly contribute to the development and progression of COVID-2019 disease. Taken together 15 drugs and 18 herb ingredients were screened as potential drugs for viral treatment. Specially, the trans-resveratrol can significantly reduce the expression of N protein of MERS-CoV and inhibit MERS-CoV. In addition, trans-resveratrol, Epigallocatechin-3-gallate (EGCG) and BX795 all show good anti multiple virus effects.

Protective effects of resveratrol on acute kidney injury in rats with sepsis.

Resveratrol significantly decreased the mortality rate of septic rats and alleviated AKI, probably by attenuating endoplasmic reticulum stress, inhibiting activation of the NF-κB pathway and mitigating the inflammatory response. --- The survival rate of cecal ligation + Res group (75.00%) significantly exceeded that of the CLP group (41.67%) (P<0.05). At postoperative 12 h, resveratrol significantly decreased serum creatinine and urea nitrogen levels (P<0.05). Resveratrol evidently relieved renal tubular swelling and luminal narrowing in CLP rats, and significantly reduced the high expressions of GRP78, BiP, phosphorylated IRE1 and p65 proteins (P<0.05). P65 was mainly located in the cytoplasm of Sham, Sham + Res and CLP + Res groups, and in the nucleus of the CLP group. At postoperative 12 h, resveratrol significantly reduced serum levels TNF-α, IL-1β and IL-6 in CLP rats (P<0.05), whereas elevated that of IL-10 (P<0.05). This has application to COVID-19 ICU treatment.

Effective inhibition of MERS-CoV infection by resveratrol.

By consecutive administration of resveratrol, we were able to reduce the concentration of resveratrol while achieving inhibitory effectiveness against MERS-CoV. CONCLUSION: In this study, we first demonstrated that resveratrol is a potent anti-MERS agent in vitro …

The upshot of Polyphenolic compounds on immunity amid COVID-19 pandemic and other emerging communicable diseases: An appraisal

Polyphenols are a large family of more than 10,000 naturally occurring compounds, which exert countless pharmacological, biological and physiological benefits for human health including several chronic diseases such as cancer, diabetes, cardiovascular, and neurological diseases. Their role in traditional medicine, such as the use of a wide range of remedial herbs (thyme, oregano, rosemary, sage, mint, basil), has been well and long known for treating common respiratory problems and cold infections. This review reports on the most highlighted polyphenolic compounds present in up to date literature and their specific antiviral perceptive properties that might enhance the body immunity facing COVID-19, and other viral infectious diseases. In fact, several studies and clinical trials increasingly proved the role of polyphenols in controlling numerous human pathogens including SARS and MERS, which are quite similar to COVID-19 through the enhancement of host immune response against viral infections by different biological mechanisms. Thus, polyphenols ought to be considered as a potential and valuable source for designing new drugs that could be used effectively in the combat against COVID‐19 and other rigorous diseases. Keywords: Polyphenols, Natural product, COVID-19, SARS, Respiratory tract, Infectious diseases

Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine

Glucose 6-phosphate dehydrogenase (G6PD) deficiency facilitates human coronavirus infection due to glutathione depletion. G6PD deficiency may especially predispose to hemolysis upon coronavirus disease-2019 (COVID-19) infection when employing pro-oxidant therapy. However, glutathione depletion is reversible by N-acetylcysteine (NAC) administration. We describe a severe case of COVID-19 infection in a G6PD-deficient patient treated with hydroxychloroquine who benefited from intravenous (IV) NAC beyond reversal of hemolysis. NAC blocked hemolysis and elevation of liver enzymes, C-reactive protein (CRP), and ferritin and allowed removal from respirator and veno-venous extracorporeal membrane oxygenator and full recovery of the G6PD-deficient patient. NAC was also administered to 9 additional respirator-dependent COVID-19-infected patients without G6PD deficiency. NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm that warrant follow-up confirmatory studies in the setting of controlled clinical trials. Keywords: Coronavirus 19, COVID-19, N-acetylcysteine, Glutathione, Glucose 6-phosphate dehydrogenase, Mechanistic target of rapamycin, C-reactive protein, Ferritin, Respirator, Extracorporeal membrane oxygenation

Potential therapeutic effects of Resveratrol against SARS-CoV-2

Home Acta Virologica 2020 Acta Virologica Vol.64, No.3, p.276-280, 2020 --- Novel Coronavirus COVID-19 or Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), are human pathogens. Current pandemics of SARS-CoV-2 represents a major health problem worldwide, with over four million cases and more than 300,000 deaths in the world. Development of effective therapy thus became an emergency. This report aims to highlight Resveratrol as possible therapeutic candidate in SARS-CoV-2 infection. The antiviral efficacy of Resveratrol was demonstrated for several viruses, including coronavirus. Resveratrol was shown to mitigate the major pathways involved in the pathogenesis of SARS-CoV-2, including regulation of the renin-angiotensin system (RAS) and expression of angiotensin-converting enzyme 2 (ACE2), stimulation of immune system and downregulation of pro-inflammatory cytokines release. It was also reported to promote SIRT1 and p53 signaling pathways and increase cytotoxic T lymphocytes (CTLs) and natural killer (NK) immune cells. In addition, Resveratrol was demonstrated to be a stimulator of fetal hemoglobin and a potent antioxidant, by trapping reactive oxygen species (ROS). According to these reports, Resveratrol could be proposed as potential therapeutics in the treatment of SARS-CoV-2. Keywords: SARS-CoV-2; Resveratrol; antiviral activity; immune response; ACE2; oxidative stress; HbF.

Medical journal article shows several key aspects of RESV and virus inhibition against another highly virulent virus in pigs.

Antiviral properties of resveratrol against pseudorabies virus are associated with the inhibition of IκB kinase activation. (Note, this study is not about COVID-19 directly, however its illustrative of how RESV can work to prevent and/or atetnuate a much more pathogenic virus that infects the brain in a way that is relevant to COVID-19, when we consider that RESV has similarly been shown to inhibit the SARS-CoV-2 virus (as well as MERS and SARS-CoV-1) in vitro, in the lab.

Stilbene-based natural compounds as promising drug candidates against COVID-19

Note that resveratrol is already available in the supply chain and inexpensive. J Biomol Struct Dyn . 2020 May 12;1-10. doi: 10.1080/07391102.2020.1762743. Online ahead of print. Hussain Mustatab Wahedi , Sajjad Ahmad , Sumra Wajid Abbasi PMID: 32345140 DOI: 10.1080/07391102.2020.1762743 The pandemic coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a great threat to public health. Currently, no potent medicine is available to treat COVID-19. Quest for new drugs especially from natural plant sources is an area of immense potential. The current study aimed to repurpose stilbenoid analogs, reported for some other biological activities, against SARS-CoV-2 spike protein and human ACE2 receptor complex for their affinity and stability using molecular dynamics simulation and binding free energy analysis based on molecular docking. Four compounds in total were probed for their binding affinity using molecular docking. All of the compounds showed good affinity (> -7 kcal/mol). However, fifty nanoseconds molecular dynamic simulation in aqueous solution revealed highly stable bound conformation of resveratrol to the viral protein: ACE2 receptor complex. Net free energy of binding using MM-PBSA also affirmed the stability of the resveratrol-protein complex. Based on the results, we report that stilbene based compounds in general and resveratrol, in particular, can be promising anti-COVID-19 drug candidates acting through disruption of the spike protein. Our findings in this study are promising and call for further in vitro and in vivo testing of stiblenoids, especially resveratrol against the COVID-19. Stilbenoid analogs could be potential disruptors of SARS-CoV-2 spike protein and human ACE2 receptor complex.In particular, resveratrol revealed highly stable conformation to the viral protein: ACE2 receptor complex.The strong interaction of resveratrol is affirmed by molecular dynamic simulation studies and better net free energies. Keywords: COVID-19; MM-PBSA; Stilbenoids; molecular docking; molecular dynamic simulations

Potential therapeutic effects of Resveratrol against SARS-CoV-2 (COVID-19)

"This report aims to highlight Resveratrol as possible therapeutic candidate in SARS-CoV-2 infection. The antiviral efficacy of Resveratrol was demonstrated for several viruses, including coronavirus. Resveratrol was shown to mitigate the major pathways involved in the pathogenesis of SARS-CoV-2, including regulation of the renin-angiotensin system (RAS) and expression of angiotensin-converting enzyme 2 (ACE2), stimulation of immune system and downregulation of pro-inflammatory cytokines release. It was also reported to promote SIRT1 and p53 signaling pathways and increase cytotoxic T lymphocytes (CTLs) and natural killer (NK) immune cells. In addition, Resveratrol was demonstrated to be a stimulator of fetal hemoglobin and a potent antioxidant, by trapping reactive oxygen species (ROS). According to these reports, Resveratrol could be proposed as potential therapeutics in the treatment of SARS-CoV-2. " Keywords: SARS-CoV-2; Resveratrol; antiviral activity; immune response; ACE2; oxidative stress; HbF. -- Acta Virol . 2020 Sep 28. doi: 10.4149/av_2020_309. Online ahead of print.

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease has a mild or even asymptomatic progression. A common denominator in all conditions associated with COVID-19 appears to be the impaired redox homeostasis responsible for reactive oxygen species (ROS) accumulation; therefore, levels of glutathione (GSH), the key anti-oxidant guardian in all tissues, could be critical in extinguishing the exacerbated inflammation that triggers organ failure in COVID-19. The present review provides a biochemical investigation of the mechanisms leading to deadly inflammation in severe COVID-19, counterbalanced by GSH. The pathways competing for GSH are described to illustrate the events concurring to cause a depletion of endogenous GSH stocks. Drawing on evidence from literature that demonstrates the reduced levels of GSH in the main conditions clinically associated with severe disease, we highlight the relevance of restoring GSH levels in the attempt to protect the most vulnerable subjects from severe symptoms of COVID-19. Finally, we discuss the current data about the feasibility of increasing GSH levels, which could be used to prevent and subdue the disease. Keywords: SARS-CoV-2, angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), glutathione, inflammation, ROS, N-acetylcysteine, NAC, glycine.