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Coronavirus disease 2019 (COVID-19) is a rapidly growing pandemic that requires urgent therapeutic intervention. Finding potential anti COVID-19 drugs aside from approved vaccines is progressively going on. The chemically diverse natural products represent valuable sources for drug leads. In this study, we aimed to find out safe and effective COVID-19 protease inhibitors from a library of natural products which share the main nucleus/skeleton of FDA-approved drugs that were employed in COVID-19 treatment guidelines or repurposed by previous studies. Our library was subjected to virtual screening against SARS-CoV Main protease (Mpro) using Molecular Operating Environment (MOE) software. Twenty-two out of those natural candidates showed higher binding scores compared to their analogues. We repurpose these natural products including alkaloids, glucosinolates, and phenolics as potential platforms for the development of anti-SARS-CoV-2 therapeutics. This study paves the way towards discovering a lead used in the treatment of COVID-19 from natural sources and introduces phytomedicines with dual therapeutic effects against COVID-19 besides their original pharmacological effects. We recommend further in vitro evaluation of their anti-COVID-19 activity and future clinical studies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Acrylamide (AA) is a hazardous chemical that is widely used in industrial practices. Spirulina platensis (SP) is a blue green alga that is rich in bioactive compounds with many medicinal benefits. The aim of the present study was to evaluate the ameliorative effect of SP against AA toxicity in rats. Animals were divided into six groups: Group (1) was normal rats, groups (2) and (3) received SP at 500 and 1000 mg/kg BW orally respectively for 21 days, group (4) was administered 20 mg/kg BW AA daily for 14 days, while groups (5) and (6) were given orally SP at the same doses of groups (2) and (3), then AA at similar dose of group (4). Rats that received AA alone displayed markedly increased serum levels of liver enzymes (ALT, AST, and ALP), kidney function parameters (urea and creatinine), DNA damage marker (8-OHdG), and proinflammatory cytokines (IL-1β, IL-6, and TNF-α), compared to control rats. Furthermore, tissue analysis revealed marked increases in hepatic, renal, and brain MDA and NO, as well as marked reductions in the antioxidant biomarkers (GSH, GSH-Px, SOD, and CAT) in acrylamide-intoxicated rats. Spirulina ameliorated the alterations in serum biochemical parameters and reduced MDA and NO, as well as improved antioxidant biomarkers in AA-intoxicated rats in a dose-dependent manner. Our results show that SP has a powerful protective effect on serum biochemistry and liver, kidney, and brain antioxidant machinery in AA-intoxicated rats.

Purpose: The effects of caffeine on drowsiness and reaction time in patients with narcolepsy are unclear. We aimed to assess the effects of caffeine as add-on therapy in narcolepsy patients., Methods: A randomized, double-blind, placebo-control clinical pilot trial was conducted with a parallel, two-arm trial allocation ratio of 1:1. Participants attended two study visits 7 days apart. The drug was administered orally in a single opaque capsule containing 200 mg caffeine/placebo daily in the morning for 1 week. Sleepiness was assessed objectively using infrared reflectance oculography to measure the percentage of long eye closure (LEC%) and subjectively using two sleepiness scales, the Stanford Sleepiness Scale (SSS) and Karolinska Sleepiness Scale (KSS). Parameters were measured at baseline (BL) prior to taking the drug, after taking the first dose (FD), and after 1 week (WD) of daily caffeine., Results: Sixteen participants with narcolepsy were included. No significant differences between groups in baseline measurements were observed. LEC% was significantly decreased after the FD and WD compared with baseline levels (BL 1.4 ± 2.1 vs. FD 0.06 ± 0.0.6 and WD 0.03 ± 0.04). Significant improvements in alertness were observed using the KSS when comparing BL with FD and WD (6.3 ± 1.6, 4.9 ± 1.7, and 4.7 ± 1.7, respectively; p = 0.01). No changes in reaction time or SSS scores were noted., Conclusion: Our findings suggest that a small dose of caffeine has positive effects on alertness in patients with narcolepsy. However, larger trials are required to confirm these findings., Trial Registration No: ClinicalTrial.gov NCT02832336.