Green and efficient one-pot three-component synthesis of novel drug-like furo[2,3-d]pyrimidines as potential active site inhibitors and putative allosteric hotspots modulators of both SARS-CoV-2 MPro and PLPro.

In this paper, an environmentally benign, convenient, and efficient one-pot three-component reaction has been developed for the regioselective synthesis of novel 5-aroyl(or heteroaroyl)-6-(alkylamino)-1,3-dimethylfuro[2,3-d]pyrimidine-2,4(1H,3H)-diones (4a‒n) through the sequential condensation of aryl(or heteroaryl)glyoxal monohydrates (1a‒g), 1,3-dimethylbarbituric acid (2), and alkyl(viz. cyclohexyl or tert-butyl)isocyanides (3a or 3b) catalyzed by ultra-low loading ZrOCl2•8H2O (just 2 mol%) in water at 50 ˚C. After synthesis and characterization of the mentioned furo[2,3-d]pyrimidines (4a‒n), their multi-targeting inhibitory properties were investigated against the active site and putative allosteric hotspots of both SARS-CoV-2 main protease (MPro) and papain-like protease (PLPro) based on molecular docking studies and compare the attained results with various medicinal compounds which approximately in three past years were used, introduced, and or repurposed to fight against COVID-19. Furthermore, drug-likeness properties of the mentioned small heterocyclic frameworks (4a‒n) have been explored using in silico ADMET analyses. Interestingly, the molecular docking studies and ADMET-related data revealed that the novel series of furo[2,3-d]pyrimidines (4a‒n), especially 5-(3,4-methylendioxybenzoyl)-6-(cyclohexylamino)-1,3-dimethylfuro[2,3-d]pyrimidine-2,4(1H,3H)-dione (4g) as hit one is potential COVID-19 drug candidate, can subject to further in vitro and in vivo studies. It is worthwhile to note that the protein-ligand-type molecular docking studies on the human body temperature-dependent MPro protein that surprisingly contains zincII (ZnII) ion between His41/Cys145 catalytic dyad in the active site, which undoubtedly can make new plans for designing novel SARS-CoV-2 MPro inhibitors, is performed for the first time in this paper, to the best of our knowledge.

Prevalence of generalized anxiety disorder among nursing students in Iran during the COVID-19 pandemic: A web-based cross-sectional study.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) is a public health emergency that poses anxiety symptoms to nursing students (P. Li et al., 2020). Therefore, this study aimed to examine the prevalence of anxiety and its associated factors in nursing students in Iran during the COVID-19 pandemic. METHODS: We performed this web-based cross-sectional study on 174 nursing students in Iran, between 4 and 24 April 2020. Data were collected through an online questionnaire using social media like Telegram and WhatsApp. Anxiety was measured via the Generalized Anxiety Disorder-7 (GAD-7). Simple and multiple logistic regression analyses were undertaken to examine independent predictors of anxiety. Statistical analysis was performed using SPSS for Windows, version 16.0. RESULTS: The mean GAD-7 total score was 6.05 ± 4.77, and the prevalence of GAD using a cut-off value of 10 for the GAD-7 was 20.7%. According to the adjusted analysis, GAD was significantly associated with having chronic diseases (OR = 5.74, 95% CI: 1.39-23.72), long time thinking about COVID-19 (OR = 14.09, 95% CI: 4.36-45.54), and death of family members, relatives or friends due to COVID-19 (OR = 4.53, 95% CI: 1.08-18.93). CONCLUSION: The prevalence of GAD is considerably high in nursing students during the COVID-19 pandemic in Iran. Thus, a holistic approach, including management policies, psychosocial interventions, and training, is critical to reducing anxiety symptoms during the COVID-19 pandemic as well as during any outbreaks of other infectious diseases in the future.

COVID-19 Associated Reversible Cerebral Vasoconstriction Syndrome Successfully Treated with Nimodipine and Aspirin.

There have been limited cases linking SARS-CoV-2 infection with the development of reversible cerebral vasoconstriction syndrome (RCVS). We hereby report a rare case of RCVS in the setting of mild SARS-CoV-2 respiratory infection successfully treated with nimodipine and aspirin. SARS-CoV-2 attacks the ACE2-receptors, which are expressed in various body organs including the lungs, kidneys, and blood vessels. Vasoconstriction can result from down-regulation of the ACE2-receptors that can lead to sympathetic hypertonia of the cerebral blood vessel walls and/or over-activation of the renin-angiotensin axis.