Inducible nitric oxide synthase deficiency promotes murine-ß-coronavirus induced demyelination.

BACKGROUND: Multiple sclerosis (MS) is characterized by neuroinflammation and demyelination orchestrated by activated neuroglial cells, CNS infiltrating leukocytes, and their reciprocal interactions through inflammatory signals. An inflammatory stimulus triggers inducible nitric oxide synthase (NOS2), a pro-inflammatory marker of microglia/macrophages (MG/Mφ) to catalyze sustained nitric oxide production. NOS2 during neuroinflammation, has been associated with MS disease pathology; however, studies dissecting its role in demyelination are limited. We studied the role of NOS2 in a recombinant ß-coronavirus-MHV-RSA59 induced neuroinflammation, an experimental animal model mimicking the pathological hallmarks of MS: neuroinflammatory demyelination and axonal degeneration. OBJECTIVE: Understanding the role of NOS2 in murine-ß-coronavirus-MHV-RSA59 demyelination. METHODS: Brain and spinal cords from mock and RSA59 infected 4-5-week-old MHV-free C57BL/6 mice (WT) and NOS2-/- mice were harvested at different disease phases post infection (p.i.) (day 5/6-acute, day 9/10-acute-adaptive and day 30-chronic phase) and compared for pathological outcomes. RESULTS: NOS2 was upregulated at the acute phase of RSA59-induced disease in WT mice and its deficiency resulted in severe disease and reduced survival at the acute-adaptive transition phase. Low survival in NOS2-/- mice was attributed to (i) high neuroinflammation resulting from increased accumulation of macrophages and neutrophils and (ii) Iba1 + phagocytic MG/Mφ mediated-early demyelination as observed at this phase. The phagocytic phenotype of CNS MG/Mφ was confirmed by significantly higher mRNA transcripts of phagocyte markers-CD206, TREM2, and Arg1 and double immunolabelling of Iba1 with MBP and PLP. Further, NOS2 deficiency led to exacerbated demyelination at the chronic phase as well. CONCLUSION: Taken together the results imply that the immune system failed to control the disease progression in the absence of NOS2. Thus, our observations highlight a protective role of NOS2 in murine-ß-coronavirus induced demyelination.

Molecular Docking Identifies Novel Phytochemical Inhibitors Against SARS-COV-2 for Covid-19 Therapy

SARS-CoV-2 the new strain of SARS corona virus is an RNA virus that inflicts acute respiratory distress syndrome due to infection of the alveolar epithelial cells, its primary target. No effective drug is currently available to treat this viral infection. Therefore, we focused on identifying inhibitors of the main viral protease domain (Mpro) which plays important role in the virus life cycle. Two tired computer-aided drug discovery approach were adopted for screening of novel inhibitors against Mpro, the target protein. First, based on their ADME/T properties, phytochemicals as well as synthetic drugs six compounds were selected from the available database. In second screening by molecular docking based on binding affinity and molecular interactions of these compounds with Mpro led to the identification of the best phytochemical and synthetic compound against Mpro. The result of docking complex showed that, interacting residues for myricetin are continuous while, in case of fosamprenavir, these are non-contiguous. Both molecules interact with the residues in the active site occupying the site for the catalytic activity indicate possible competitive inhibitors of the Mpro.

Effect of Covid-19 pandemic induced lockdown on sleep wake pattern and personal well-being of undergraduate medical students of West Bengal

Background: COVID-19 pandemic induced lockdown and the social restrictions had a profound impact on the circadian rhythm driven sleep-wake schedule of the home confined population. Aims and Objective: Our study explored the effect of COVID-19 pandemic induced lockdown on sleep wake pattern and personal well-being of medical students of West Bengal. Materials and Methods: An observational, questionnaire-based online survey was conducted using the URL linked Google form. The online survey was conducted through social media platforms as per CHERRIES checklist guideline. Information on demographic profile, before and after lockdown sleep-wake pattern, social wellbeing and general lifestyle was obtained. Any student with any sleeping disorder or on drugs was excluded. Mean (SE), median, range, proportion was calculated as per attributes. Fisher's exact chi square test and paired t test was done to test association and to compare means of the attributes. Results: The mean age of students was 20.26 years. The average daily time spent on electronic media got doubled during lockdown. Sleep disorder was reported by 53.0% male and 47.0% students. More than half of respondents reported increased napping during daytime, irregular timing for meal intake and low mood. Anxiety was present in every two out of three participants. Females gained more weight during lockdown. The gender difference in sleep duration became significant. Lockdown effect on the average daily media time was significant. The sleep disturbance at night and physical inactivity was significantly more among female students. Conclusion: COVID-19 lockdown leads to delayed sleep-wake cycle, irregular meal timings and excessive digital exposure among medical students with gender based differential impact. [ABSTRACT FROM AUTHOR] Copyright of Asian Journal of Medical Sciences is the property of Manipal Colleges of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Online teaching during COVID19 pandemic in different medical Institutions of West Bengal- From student's perspective

Background: Social distancing is important preventive strategy to prevent spreading of SARSCOV- 2. The medical faculties are continuing the teaching-learning session using different online platform. Aims and Objective: This online survey aims at exploring the different aspect of online teaching effects among medical students. Materials and Methods: Forty-four validated questions in the Google survey form were distributed among the MBBS students of different medical colleges of West Bengal in this cross-sectional study, and analysed. Results: The responses from 416 participants show that internet-based teaching has been adopted by 96.4% of colleges. Practical class and classes regarding clinical exposure are the two most neglected section of the MBBS curriculum during this pandemic. Total teaching hours per day also drastically reduced from mean of 5.56 h/ day in pre-pandemic time to 1.95 h/ day during this pandemic. Out of 69.7% of the participants who faced difficulty in following online classes, majority (56.25%) was due to technical problems including issues related to internet connectivity and software. Participants were of opinion that current session should be extended on an average of 3 months as the practical and clinical classes are way behind in syllabus completion. According to 72.35% of participants, online classes are less effective than the offline classes. Conclusions: In nutshell, online teaching activities cannot replace the classical classroom teaching, though it is a cost-effective and viable method during this pandemic period. [ABSTRACT FROM AUTHOR] Copyright of Asian Journal of Medical Sciences is the property of Manipal Colleges of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Protective Potentials of Type III Interferons in COVID-19 Patients: Lessons from Differential Properties of Type I- and III Interferons.

While an appropriately regulated production of interferons (IFNs) performs a fundamental role in the defense against coronaviruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), dysregulated overproduction of inflammatory mediators can play an important role in the development of SARS-CoV-2 infection-related complications, such as acute respiratory distress syndrome. As the principal constituents of innate immunity, both type I and III IFNs share antiviral features. However, important properties, including preferential expression at mucosal barriers (such as respiratory tract), local influences, lower receptor distribution, smaller target cell types, noninflammatory effects, and immunomodulatory impacts, were attributed only to type III IFNs. Accordingly, type III IFNs can establish an optimal effective antiviral response, without triggering exaggerated systemic inflammation that is generally attributed to the type I IFNs. However, some harmful effects were attributed to the III IFNs and there are also major differences between human and mouse concerning the immunomodulatory effects of III IFNs. Here, we describe the differential properties of type I and type III IFNs and present a model of IFN response during SARS-COV-2 infection, while highlighting the superior potential of type III IFNs in COVID-19.

Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions.

The COVID-19-, SARS- and MERS-related coronaviruses share many genomic and structural similarities. However, the SARS-CoV-2 is less pathogenic than SARS-CoV and MERS-CoV. Despite some differences in the cytokine patterns, it seems that the cytokine storm plays a crucial role in the pathogenesis of COVID-19-, SARS- and MERS. Monocytes and macrophages may be infected by SARS-CoV-2 through ACE2-dependent and ACE2-independent pathways. SARS-CoV-2 can effectively suppress the anti-viral IFN response in monocytes and macrophages. Since macrophages and dendritic cells (DCs) act as antigen presenting cells (APCs), the infection of these cells by SARS-CoV-2 impairs the adaptive immune responses against the virus. Upon infection, monocytes migrate to the tissues where they become infected resident macrophages, allowing viruses to spread through all organs and tissues. The SARS-CoV-2-infected monocytes and macrophages can produce large amounts of numerous types of pro-inflammatory cytokines and chemokines, which contribute to local tissue inflammation and a dangerous systemic inflammatory response called cytokine storm. Both local tissue inflammation and the cytokine storm play a fundamental role in the development of COVID-19-related complications, such as acute respiratory distress syndrome (ARDS), which is a main cause of death in COVID-19 patients. Here, we describe the monocytes and macrophage responses during severe coronavirus infections, while highlighting potential therapeutic interventions to attenuate macrophage-related inflammatory reactions in possible approaches for COVID-19 treatment.