Biobran/MGN-3, an Arabinoxylan Rice Bran, Protects against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An In Vitro and In Silico Study.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), poses a serious global public health threat for which there is currently no satisfactory treatment. This study examines the efficacy of Biobran/MGN-3 against SARS-CoV-2. Biobran is an arabinoxylan rice bran that has been shown to significantly inhibit the related influenza virus in geriatric subjects. Here, Biobran's anti-SARS-CoV-2 activity was assessed using MTT and plaque reduction assays, RT-PCR, ELISA techniques, and measurements of SARS-CoV-2-related gene expression and protein levels. For Vero E6 cells infected with SARS-CoV-2, Biobran reduced the viral load by 91.9% at a dose of 100 µg/mL, it reduced viral counts (PFU/mL) by 90.6% at 50 µg/mL, and it exhibited a significant selectivity index (EC50/IC50) of 22.5. In addition, Biobran at 10 µg/mL inhibited papain-like proteinase (PLpro) by 87% and ACE2 SARS-CoV-2 S-protein RBD by 90.5%, and it significantly suppressed SARS-CoV-2 gene expression, down-regulating E-gene and RdRp gene expression by 93% each at a dose of 50 µg/mL and inhibiting the E-protein by 91.3%. An in silico docking study was also performed to examine the protein-protein interaction (PPI) between SARS-CoV-2 RBD and DC-SIGN as well as between serine carboxypeptidase and papain-like protease PLpro. Serine carboxypeptidase, an active ingredient in Biobran, was found to interfere with the binding of SARS-CoV-2 to its receptor DC-SIGN on Vero cells, thus preventing the cell entry of SARS-CoV-2. In addition, it impairs the viral replication cycle by binding to PLpro. We conclude that Biobran possesses potent antiviral activity against SARS-CoV-2 in vitro and suggest that Biobran may be able to prevent SARS-CoV-2 infection. This warrants further investigation in clinical trials.

Partial-Methylated HeyL Promoter Predicts the Severe Illness in Egyptian COVID-19 Patients.

Background: To date (14 January 2022), the incidence and related mortality rate of COVID-19 in America, Europe, and Asia despite administrated of billions doses of many approved vaccines are still higher than in Egypt. Epigenetic alterations mediate the effects of environmental factors on the regulation of genetic material causing many diseases. Objective: We aimed to explore the methylation status of HeyL promoter, a downstream transcription factor in Notch signal, an important regulator of cell proliferation and differentiation blood, pulmonary epithelial, and nerves cells. Methods: Our objective was achieved by DNA sequencing of the product from methyl-specific PCR of HeyL promoter after bisulfite modification of DNA extracted from the blood samples of 30 COVID-19 patients and 20 control health subjects and studying its association with clinical-pathological biomarkers. Results: We found that the HeyL promoter was partial-methylated in Egyptian COVID-19 patients and control healthy subjects compared to full methylated one that was published in GenBank. We identified unmethylated CpG (TG) flanking the response elements within HeyL promoter in Egyptian COVID-19 patients and control healthy subjects vs. methylated CpG (CG) in reference sequence (GenBank). Also, we observed that the frequency of partial-methylated HeyL promoter was higher in COVID-19 patients and associated with aging, fever, severe pneumonia, ageusia/anosmia, and dry cough compared to control healthy subjects. Conclusion: We concluded that hypomethylated HeyL promoter in Egyptian population may facilitate the binding of transcription factors to their binding sites, thus enhancing its regulatory action on the blood, pulmonary epithelium, and nerves cells in contrast to full methylated one that was published in GenBank; thus, addition of demethylating agents to the treatment protocol of COVID-19 may improve the clinical outcomes. Administration of therapy must be based on determination of methylation status of HeyL, a novel prognostic marker for severe illness in COVID-19 patients.

After Successful of Tocilizumab Plus Micronutrients in The Treatment of COVID19 Patients;Cosentyx May Be Recommended

By 23rd August 2020, 23,057,288 confirmed cases with SARS-CoV-2 that causes 800,906 deaths worldwide. The severe illness and high mortality are attributed to the dysregulation of hematopoiesis accompanied by cytokines storm. The severe illness and high mortality rate confirm the failure of the conventional strategy in the treatment of COVID19 patients. Also, lack of a specific vaccine or therapies target for SARS-CoV-2 infection, the drug repositioning in the treatment of COVID19 patients is the only opportunity to face this pandemic. Thus, we highlight the implication of a novel strategy of treatment based on the inhibition of IL-6, the major player in a cytokine storm, using Tocilizumab, in combination with micronutrients including Zinc, Selenium, vitamin C, and Glutathione. Application of Tocilizumab in infectious diseases is considered as a new treatment protocol since its usual uses are in autoimmune diseases. In the present study, we analyze the data for COVID19 patients who showed cytokine storm due to elevated level of IL-6 and suffered from severe illness, fever, ARDS, and transferred to ICU in Armed Forces Hospital. We found that Tocilizumab plus micronutrients improves the clinical outcomes in these critical cases of COVID19 patients. Statistical analyses of biochemical parameters including complete blood count to evaluate the efficacy of this combined therapy on counteracting the effect of SARS-CoV-2 on the differential of blood cell ratios, pro-inflammatory parameters (CRP, Ddimer, and ferritin), liver, cardiac, and kidney function were carried out. Finally, based on the success of Tocilizumab, an IL-6 inhibitor, in the treatment of COVID19 patients, we recommend using Cosentyx that is an inhibitor of IL-17, a partner of IL-6 in the inflammation process.