Exploring the dual effect of novel 1,4-diarylpyranopyrazoles as antiviral and anti-inflammatory for the management of SARS-CoV-2 and associated inflammatory symptoms.

COVID-19 and associated substantial inflammations continue to threaten humankind triggering death worldwide. So, the development of new effective antiviral and anti-inflammatory medications is a major scientific goal. Pyranopyrazoles have occupied a crucial position in medicinal chemistry because of their biological importance. Here, we report the design and synthesis of a series of sixteen pyranopyrazole derivatives substituted with two aryl groups at N-1 and C-4. The designed compounds are suggested to show dual activity to combat the emerging Coronaviruses and associated substantial inflammations. All compounds were evaluated for their in vitro antiviral activity and cytotoxicity against SARS-CoV infected Vero cells. As well, the in vitro assay of all derivatives against the SARS-CoV Mpro target was performed. Results revealed the potential of three pyranopyrazoles (22, 27, and 31) to potently inhibit the viral main protease with IC50 values of 2.01, 1.83, and 4.60 µM respectively compared with 12.85 and 82.17 µM for GC-376 and lopinavir. Additionally, in vivo anti-inflammatory testing for the most active compound 27 proved its ability to reduce levels of two cytokines (TNF-α and IL-6). Molecular docking and dynamics simulation revealed consistent results with the in vitro enzymatic assay and indicated the stability of the putative complex of 27 with SARS-CoV-2 Mpro. The assessment of metabolic stability and physicochemical properties of 27 have also been conducted. This investigation identified a set of metabolically stable pyranopyrazoles as effective anti-SARS-CoV-2 Mpro and suppressors of host cell cytokine release. We believe that the new compounds deserve further chemical optimization and evaluation for COVID-19 treatment.

In vitro and computational investigations of novel synthetic carboxamide-linked pyridopyrrolopyrimidines with potent activity as SARS-CoV-2-MPro inhibitors† † Electronic supplementary information (ESI) available. See https://doi.org/10.1039/d2ra04015h

An essential target for COVID-19 is the main protease of SARS-CoV-2 (Mpro). With the objective of targeting this receptor, a novel set of pyrido[1,2-a]pyrrolo[2,3-d]pyrimidines with terminal carboxamide fragments was designed, synthesized, and considered as an initial motif for the creation of effective pan-coronavirus inhibitors. Accordingly, nine derivatives (21–29) have been introduced for in vitro assay to evaluate their antiviral activity and cytotoxicity effect against COVID-19 virus using Vero cells. The obtained data revealed that the majority of these derivatives showed potent cellular anti-COVID-19 activity and prevent viral growth by more than 90% at two different concentrations with weak or even no detectable cytotoxic effect on Vero cells. Extensive molecular docking simulations highlighted proper non-covalent interaction of new compounds within the binding pocket of Mpro as a potential target for their antiviral activity. In vitro assay for all the synthesized derivatives against the viral Mpro target indicated that compounds 25 and 29 have promising inhibitory activity with IC50 values at low micromolar concentrations. The molecular dynamic simulation results predicted the stability of compound 29 in the binding cavity of SARS-CoV-2 Mpro and hence supported the high inhibitory activity shown by the In vitro assay. These results suggested that compounds 25 and 29 merit further investigations as promising drug candidates for the management of SARS-CoV-2. An essential target for COVID-19 is the main protease of SARS-CoV-2 (Mpro).

In vitro and computational investigations of novel synthetic carboxamide-linked pyridopyrrolopyrimidines with potent activity as SARS-CoV-2-MPro inhibitors.

An essential target for COVID-19 is the main protease of SARS-CoV-2 (Mpro). With the objective of targeting this receptor, a novel set of pyrido[1,2-a]pyrrolo[2,3-d]pyrimidines with terminal carboxamide fragments was designed, synthesized, and considered as an initial motif for the creation of effective pan-coronavirus inhibitors. Accordingly, nine derivatives (21-29) have been introduced for in vitro assay to evaluate their antiviral activity and cytotoxicity effect against COVID-19 virus using Vero cells. The obtained data revealed that the majority of these derivatives showed potent cellular anti-COVID-19 activity and prevent viral growth by more than 90% at two different concentrations with weak or even no detectable cytotoxic effect on Vero cells. Extensive molecular docking simulations highlighted proper non-covalent interaction of new compounds within the binding pocket of Mpro as a potential target for their antiviral activity. In vitro assay for all the synthesized derivatives against the viral Mpro target indicated that compounds 25 and 29 have promising inhibitory activity with IC50 values at low micromolar concentrations. The molecular dynamic simulation results predicted the stability of compound 29 in the binding cavity of SARS-CoV-2 Mpro and hence supported the high inhibitory activity shown by the In vitro assay. These results suggested that compounds 25 and 29 merit further investigations as promising drug candidates for the management of SARS-CoV-2.

Restructuring the inpatient advanced pharmacy practice experience to reduce the risk of contracting coronavirus disease 2019: Lessons from Saudi Arabia

Introduction: On March 11, 2020, the World Health Organization announced the rapidly spreading epidemic of the coronavirus disease 2019 (COVID-19) pandemic. Almost all countries started to take proactive precautionary measures to reduce the risk of contracting the virus. The education sector, including pharmacy education, has been drastically impacted by this pandemic. During the outbreak, many hospitals instructed the health profession's schools to restrict or prevent the presence of their students and interns in their hospitals in an effort to limit the spread of the virus. Objectives: Constraining the presence of interns in the affiliated hospital has impacted the integrity of delivering the learning outcomes of each clinical rotation. In this paper, we present the experience of four faculty preceptors in restructuring the advanced pharmacy practice experience in different clinical settings, including critical care, infectious diseases, cardiology, and internal medicine, in order to reduce the risk of contracting COVID-19 at a large academic medical institution in Saudi Arabia. Conclusion: We believe that this experience could provide guidance and insights for other pharmacy schools dealing with this issue during this global pandemic.

Video-Based Student Engagement Estimation via Time Convolution Neural Networks for Remote Learning

Given the recent outbreak of COVID-19 pandemic globally, most of the schools and universities have adapted many of the learning materials and lectures to be delivered online. As a result, the necessity to have some quantifiable measures of how the students are perceiving and interacting with this ‘new normal’ way of education became inevitable. In this work, we are focusing on the engagement metric which was shown in the literature to be a strong indicator of how students are dealing with the information and the knowledge being presented to them. In this regard, we have proposed a novel data-driven approach based on a special variant of convolutional neural networks that can predict the students’ engagement levels from a video feed of students’ faces. Our proposed framework has achieved a promising mean-squared error (MSE) score of only 0.07 when evaluated on a real dataset of students taking an online course. Moreover, the proposed framework has achieved superior results when compared with two baseline models that are commonly utilised in the literature for tackling this problem. © 2022, Springer Nature Switzerland AG.

Cerebral Venous Infarct After Recovery From COVID-19 Pneumonia.

The coronavirus disease 2019 (COVID-19) may have multisystem organ involvement. Thrombotic events are well-recognized complications of COVID-19. Such complications may include the pulmonary, renal, and other organs vasculature. The risk of coagulopathy is usually related to the severity of COVID-19 pneumonia. Few cases suggested that the coagulopathy risk may persist for some period after the recovery from COVID-19. We report the case of a middle-aged man with severe COVID-19 pneumonia that required seven days of endotracheal intubation and mechanical ventilation who presented with headache and left-sided weakness that occurred three days after his discharge. A computed tomography scan was performed to rule out intracranial hemorrhage before initiating the thrombolytic therapy. The scan demonstrated hemorrhage in the right temporal lobe with surrounding vasogenic edema along with density in the right transverse sinus. Subsequently, computed tomography venography was performed and demonstrated the filling defect representing right sigmoid venous sinus thrombosis. The patient received conservative measures in the form of intravenous hydration, anticoagulation, analgesics, and anticonvulsants. During the hospital stay, the patient had improvement in his symptom and mild neurological deficit persisted. The case highlighted that risk of thrombotic complications in COVID-19 pneumonia may persist for some period after the recovery from the disease. Hence, thromboprophylaxis may be indicated in selected patients with a risk of thrombotic events after their recovery from severe COVID-19.