Structure-Based Identification and Analysis of Viral Protease Inhibitors Targeting SARS CoV-2 Virus Replication

The re-emergence of SARS-CoV, known as SARS-CoV-2, has proven extremely infectious that has infected a huge population worldwide. SARS-CoV-2 genome is translated into polyproteins that is processed by virus-specific protease enzymes. 3CLprotease is named as the main protease (Mpro) enzyme that cleaves nsp4 to nsp16. This crucial role of Mpro makes this enzyme a prime and promising antiviral target. Till date, there is no effective commercially available drug against COVID-19 and launching a new drug into the market is a complicated and time-consuming process. Therefore, drug repurposing is a new but familiar approach to reduce the time and cost of drug discovery. We have used a high-throughput virtual screening approach to examine FDA approved library, natural compound library, and LOPAC 1280 (Library of Pharmacologically Active Compounds, Sigma-Aldrich, St. Louis, MO) library against Mpro. Primary screening identified potential drug molecules for the target, among which ten molecules were studied further using biophysical and biochemical techniques. SPR was used to validate the binding of inhibitors to purified Mpro and using FRET-based biochemical protease assay these inhibitors were confirmed to have Mpro inhibitory activity. Based on the kinetic studies, the antiviral efficacy of these compounds was further analysed by cell-culture based antiviral assays. Four out of ten molecules inhibited SARS-CoV-2 replication in Vero cells at a concentration range of 12.5 to 50 muM. The antiviral activity was evaluated by RT-PCR assay and TCID50 experiments. The co-crystallization of Mpro in complex with inhibitor for determining their structures is being carried out. Collectively, this study will provide valuable mechanistic and structural insights for development of effective antiviral therapeutics against SARS-CoV-2.

A Review on Therapeutic Potential of Indian Herbal Plants to Counter Viral Infection and Disease Pathogenesis

Herbal plant extracts or purified phytocomponents have been extensively used to treat several diseases since ancient times. The Indian Ayurvedic system and Chinese traditional medicines have documented the medicinal properties of important herbs. In Ayurveda, the polyherbal formulation is known to exhibit better therapeutic efficacy compared to a single herb. This review focuses on six key ayurvedic herbal plants namely, Tinospora cordifolia, Withania somnifera, Glycyrrhiza glabra/Licorice, Zingiber officinale, Emblica officinalis and Ocimum sanctum. These plants possess specific phytocomponents that aid them in fighting infections and keeping body healthy and stress-free. Plants were selected due to their reported antimicrobial and anti-inflammatory effects in several diseases and effectiveness in controlling viral pathogenesis. An ad-vanced literature search was carried out using Pubmed and google scholar. Result(s): These medicinal plants are known to exhibit several protective features against various diseases or infections. Here we have particularly emphasized on antioxidant, anti-inflammatory, anti-microbial and immunomodulatory properties which are common in these six plants. Recent literature analysis has revealed Ashwagandha to be protective for Covid-19 too. The formulation from such herbs can exhibit synergism and hence better effectiveness against infection and related dis-eases. The importance of these medicinal herbs becomes highly prominent as it maintains the har-monious balance by way of boosting the immunity in a human body. Further, greater mechanistic analyses are required to prove their efficacy in fighting infectious diseases like Covid-19. It opens the arena for in-depth research of identifying and isolating the active components from these herbs and evaluating their potency to inhibit viral infections as polyherbal formulations.Copyright © 2023 Bentham Science Publishers.

The Digital Divide and Smartphone Reliance for Disadvantaged Students in Higher Education

The digital divide as it pertains to information inequality among disadvantaged student populations in higher education is a pertinent problem, and has been further exacerbated by the increase in online learning due to COVID -19. This study explores Technological Access challenges of students at a small public midwestern university in the US that serves a disproportionately higher number of underserved and underrepresented students. Survey data from 535 undergraduate students indicate that a critical subset (n=61) of the sample who were first generation, low income, and non-white had significantly lower levels of technological access with respect to access to devices and Internet access, when compared to the larger sample. Additionally, nearly half of the sample used smartphones to access courses online. Educational implications on smartphone dependence and consequent digital divide is discussed to bridge the barrier for disadvantaged student groups. As technology induced online learning proliferates, addressing such gaps will be a step toward mitigating those inequities plaguing higher education. Copyright 2022. © by the International Institute of Informatics and Systemics. All rights reserved.

ECG Abnormalities in Patients Affected with COVID-19: A Review

Cardiovascular inclusion has been accounted for in patients with serious intense respiratory condition Covid 2 contamination, which might be reflected by electrocardiographic changes. Cardiovascular injury is additionally connected with humanity, need for intensive care, and seriousness of illness in patients due to Coronavirus. Some case features cardiovascular contribution as an intricacy related with Coronavirus, even without indications and indications of interstitial pneumonia. Two Coronavirus incidents in our report displayed diverse ECG indications by means of the sickness caused decay. The main case introduced brief SI QIII TIII sound structure followed by changeable almost whole atrioventricular square, and the second exhibited ST-section height joined by choroidal ventricular tachycardiac. The hidden systems of these ECGs irregularities in the serious phase of Coronavirus might be ascribed to hypoxia and incendiary harm brought about by the infection. Since the scourge of Coronavirus pulled in the consideration, hearsays were encompassing ECG variations in the contaminated people. We pointed toward indicative dissimilar noticed ECG discoveries and talking about their experimental importance. This deliberate audit recommends that recognizing ECG designs that may be connected with Coronavirus is fundamental. Given that doctors don't perceive these examples, they may mistakenly hazard the existences of their patients. Moreover, significant medication instigated ECG changes give attention to the medical care laborers on the dangers of potential treatments. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

COVID-19–a crisis of care and what we can learn from the SEWA experience in India

As women across the globe continue to be overburdened with child-care responsibilities owing to the closure of institutional child-care facilities due to the COVID-19 pandemic, this paper attempts to posit a viable disaster-resilient model through the idea of community-based care infrastructure. Based on research conducted among parents from low-income groups, whose children attended child-care centres run by Sangini Co-operative of Self-employed women's association (SEWA) in Gujarat in western India, this paper wants to highlight the spontaneity with which the Cooperative responded to the pandemic, underlining the efficacy of community-based interventions in times of crisis. This paper argues that solidarity between care workers and the larger community is only likely to increase during times of crisis, which makes community-based solutions an integral part of addressing future care emergencies. © 2022 Oxfam KEDV.

Immuno-Epidemiological Model-Based Prediction of Further Covid-19 Epidemic Outbreaks Due to Immunity Waning

We develop a new data-driven immuno-epidemiological model with distributed infectivity, recovery and death rates determined from the epidemiological, clinical and experimental data. Immunity in the population is taken into account through the time-dependent number of vaccinated people with different numbers of doses and through the acquired immunity for recovered individuals. The model is validated with the available data. We show that for the first time from the beginning of pandemic COVID-19 some countries reached collective immunity. However, the epidemic continues because of the emergence of new variant BA.2 with a larger immunity escape or disease transmission rate than the previous BA.l variant. Large epidemic outbreaks can be expected several months later due to immunity waning. These outbreaks can be restrained by an intensive booster vaccination.

Dheas/ cortisol ratio acts as a better surrogate marker of inflammation than dheas or cortisol in patients with COVID-19

Objective : Dehydroepiandrosterone sulfate (DHEAS) was observed to be decreased in sepsis and inflammatory conditions. The severity of inflammation was found to be associated with a low DHEAS/cortisol ratio. In the present study, we compared DHEAS, cortisol, and DHEAS/cortisol ratio to assess which is a better marker for inflammation in patients with COVID-19. Methodology: This was an analytical cross-sectional pilot study conducted from April 2020 to Dec 2020. The study recruited 76 RT-PCR positive COVID-19 positive patients. The blood samples were collected were analyzed for cortisol and DHEAS. Highly sensitive C-reactive protein (hs-CRP) levels were estimated to assess the inflammation. Results: We classified the cases into two groups based on the median levels of DHEAS, cortisol, and DHEAS/cortisol ratio. We observed hs-CRP to be elevated in the groups which have the levels of DHEAS, cortisol, and DHEAS/cortisol ratio lower than the respective medians. However, a significant difference in hs-CRP levels was observed only between DHEAS/cortisol ratio (p value= 0.0204) and not between DHEAS and cortisol groups. Conclusion: The present study is the first of its kind comparing the DHEAS levels and DHEAS/ cortisol ratio in COVID-19. The study concludes DHEAS/cortisol ratio to be a better marker than individual DHEAS or cortisol in the assessment of inflammation in COVID-19 patients.

Measuring the Impact of an IoT Temperature Sensor Framework for Tracking Contagious Diseases

Due to the COVID-19 pandemic, much computer science research has been dedicated to utilizing sensor readings for medical purposes. Throughout this period, the need for virus symptom tracking has become a promising area for remotely deployed sensor networks and platforms. Our research goal is to prove that the temperature readings from these sensor network platforms can be statistically linked to public record, medical case study data. The expected outcome of our project is to prove the correlation between sensor network tracking of remote human temperature data and medical records for COVID cases. The results of this study will prove that tracking human temperature can assist in tracking disease outbreaks in various populations. Our framework platform is comprised of four main modules: (1) Temperature Collection, (2) Internal Data Validation (3) Internal-External data merger, (4) Data Analytics. The temperature data are collected from internal databases, mobile sensing devices and medical health professionals. After collection, the internal data are validated by our software, TAU-FIVE, a multi-tier data quality validation system, then merged with external data sources into a data analytic based data warehouse. The data mart queries are designed to compare the location and date of temperature sensor data with known data sets from government officials. Once blended into a fully operational data warehouse, these data marts produce high quality data analysis linking remotely sensed human temperature readings to sources of disease outbreaks. © 2021 IEEE.

HIV-1 and SARS-CoV2 both cause protein s, but through different mechanisms

Background : The anticoagulant protein S (PS) circulates in two plasma pools: free (functional) or bound to complement factor 4-binding protein (c4bp). PS deficiency commonly occurs in Human Immunodeficiency Virus-1 (HIV-1)+ patients and is associated with thrombosis. We hypothesized a similar process contributes to thrombosis in COVID-19. Aims : To assess the regulation of PS in viral coagulopathies. Methods : This study was approved by the Institutional Review Board. Citrated plasma was collected from consenting HIV-1+ (19 naïve, 11 on antiretroviral therapy, ART) or SARS-CoV-2+ (28 inpatients, 49 outpatients) and healthy controls for both populations (10, 31, respectively). Results : HIV-1+ patients had lower total PS than controls (94.12 ± 8.71% vs 133.77 ± 10.45%, P = 0.008), in both naïve (42%) and ART-treated (27%) patients. Total PS negatively correlated with endogenous thrombin potential ( P = 0.01), suggesting PS deficiency contributes to increased thrombin generation in these patients. Total PS was not reduced in SARS-CoV-2+ patients, but free PS was (Table). To determine the cause of free PS deficiency, we measured known PS-binding proteins C4bp, protein C (PC), and Mer, and found no differences between patients and controls. By native gel, we identified PS bound to C4bp, Mer, PC, tissue factor pathway inhibitor (TFPI), and von Willebrand Factor (VWF). VWF was markedly elevated in inpatients. Purified VWF dose-dependently decreased free, but not total, PS when added to control plasma, and blocked the TFPI cofactor activity of PS. PS was also identified as a plasma binding partner of VWF by mass spectrometry, and this interaction increased 10-million-fold with shearing. Finally, despite anticoagulation, plasma thrombin generation in inpatient samples was comparable to controls, suggesting a profound hypercoagulability, possibly exacerbated by PS deficiency. Conclusions : In HIV-1, PS consumption leads to total PS deficiency. In SARS-CoV-2, VWF increases and binds PS, reducing the free pool. Thus, viruses can cause PS deficiency through multiple mechanisms, promoting thrombosis by shifting the procoagulant-anticoagulant balance.

Spatial behavioural responses to the spread of an infectious disease can suppress Turing and Turing-Hopf patterning of the disease

Reducing risky behaviour and/or avoiding sites where the risk of infection is perceived as higher (by social and/or spatial distancing) represent the two main forms of non-pharmaceutical behavioural responses of humans to the threats of infectious diseases. Here we investigate, within a reaction-diffusion setting, a family of new models for an endemic SIR (susceptible-infective-removed) infectious disease for which no vaccine is available and individuals' responses to the infection threat are entirely based on changes either in their social behaviour or in their mobility behaviour, that is avoiding to visit sites with a large infection prevalence. First, we derive general conditions for the onset of Turing patterns for a general family of spatially inhomogeneous SIR models with a prevalence-dependent contact rate and constant recruitment. Then, we characterize our main family of models where the behavioural response also includes a spatial component, and show the condition bringing to the mitigation, or even the destruction, of Turing patterns. The same conditions can allow the transition from Turing-Hopf spatio-temporal patterns to pure Hopf temporal patterns. The same is also done for two SIS models. These results bring an inference of interest: the reduction of spatial clustering typically observed during the course of an epidemics might be related to a combination of agents' spontaneous social and spatial distancing. To validate our theoretical results and further explore other spatio-temporal effects of the proposed spatial behavioural responses, numerical simulations of a specific instance of the above-mentioned family of SIR models have been performed. (C) 2019 Published by Elsevier B.V.

Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis.

PURPOSE: To provide a precise summary and collate the hitherto available clinical evidence on the effect of vitamin D supplementation on clinical outcomes in COVID-19 patients. METHODS: PubMed/MEDLINE, Scopus, and Web of Science databases were systematically searched using appropriate keywords till June 8, 2021, to identify observational studies and randomized controlled trials (RCTs) reporting adverse clinical outcomes (ICU admission and/or mortality) in COVID-19 patients receiving vitamin D supplementation vs. those not receiving the same. Both prior use and use of vitamin D after COVID-19 diagnosis were considered. Unadjusted/adjusted pooled odds ratio (OR) with 95% confidence intervals (CI) were calculated (PROSPERO registration number CRD42021248488). RESULTS: We identified 13 studies (10 observational, 3 RCTs) pooling data retrieved from 2933 COVID-19 patients. Pooled analysis of unadjusted data showed that vitamin D use in COVID-19 was significantly associated with reduced ICU admission/mortality (OR 0.41, 95% CI: 0.20, 0.81, p = 0.01, I2 = 66%, random-effects model). Similarly, on pooling adjusted risk estimates, vitamin D was also found to reduce the risk of adverse outcomes (pooled OR 0.27, 95% CI: 0.08, 0.91, p = 0.03, I2 = 80%, random-effects model). Subgroup analysis showed that vitamin D supplementation was associated with improved clinical outcomes only in patients receiving the drug post-COVID-19 diagnosis and not in those who had received vitamin D before diagnosis. CONCLUSIONS: Vitamin D supplementation might be associated with improved clinical outcomes, especially when administered after the diagnosis of COVID-19. However, issues regarding the appropriate dose, duration, and mode of administration of vitamin D remain unanswered and need further research.

Glycemic efficacy and safety of hydroxychloroquine in type 2 diabetes mellitus: A systematic review and meta.analysis of relevance amid the COVID-19 pandemic

Aims: Hydroxychloroquine (HCQ) is approved for use as an oral anti-diabetic drug (OAD) in patients with uncontrolled type 2 diabetes mellitus (T2DM);however, robust data are lacking. The present meta-analysis was conducted to provide precise effect estimates regarding the efficacy and safety of HCQ in patients with T2DM. Methods: PubMed/Cochrane Library and grey literature were systematically searched till August 25, 2020, to identify randomized controlled trials (RCTs) with duration =12 weeks, evaluating the efficacy and safety of HCQ (400 mg/day) in patients with T2DM and glycated hemoglobin (HbA1c) =7.0%-7.5% already on a combination of metformin/sulfonylurea compared to either placebo or another OAD. Results: We identified eight eligible RCTs, pooling data retrieved from 1763 patients with T2DM. HCQ resulted in significant decrease in HbA1c by 0.88% (95% confidence interval [CI]: -1.01 to - 0.75) compared to placebo and by 0.32% (95% CI: -0.37 to -0.26) compared to an OAD. Besides, there were significant reductions in fasting blood glucose, postprandial blood glucose, body weight, triglycerides, and low-density lipoprotein. A small but significant increase in high-density lipoprotein was also noted. An increase in the risk of any episode of symptomatic hypoglycemia (whether documented or not) was observed (risk ratio = 1.34 [95% CI: 1.10-1.63]). No other safety issues were identified. Conclusions: The meta-analysis suggests that HCQ, used as an add-on drug in patients with T2DM exerts significant beneficial effects on glycemic control, body weight, and lipid profile, however, increasing the risk for symptomatic hypoglycemia. HCQ might be useful amid the ongoing pandemic, as the drug has also been found to be beneficial in COVID-19.

A new approach to the dynamic modeling of an infectious disease

In this work we propose a delay differential equation as a lumped parameter or compartmental infectious disease model featuring high descriptive and predictive capability, extremely high adaptability and low computational requirement. Whereas the model has been developed in the context of COVID-19, it is general enough to be applicable with such changes as necessary to other diseases as well. Our fundamental modeling philosophy consists of a decoupling of public health intervention effects, immune response effects and intrinsic infection properties into separate terms. All parameters in the model are directly related to the disease and its management;we can measure or calculate their values a priori basis our knowledge of the phenomena involved, instead of having to extrapolate them from solution curves. Our model can accurately predict the effects of applying or withdrawing interventions, individually or in combination, and can quickly accommodate any newly released information regarding, for example, the infection properties and the immune response to an emerging infectious disease. After demonstrating that the baseline model can successfully explain the COVID-19 case trajectories observed all over the world, we systematically show how the model can be expanded to account for heterogeneous transmissibility, detailed contact tracing drives, mass testing endeavours and immune responses featuring different combinations of temporary sterilizing immunity, severity-reducing immunity and antibody dependent enhancement. [ABSTRACT FROM AUTHOR] Copyright of Mathematical Modelling of Natural Phenomena is the property of EDP 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.)

Cortisol and COVID-19—Putting Undue Stress on the “Stress Hormone”

Serum cortisol is a measure of underlying disease severity. The more severe the disease, the higher the circulating cortisol levels and the greater the chances of poor prognosis/mortality. Not surprisingly, a recent study found that higher serum cortisol was associated with poor prognosis in patients with coronavirus disease 2019 (COVID-19). Nevertheless, the study did not take into consideration the confounding effect of COVID-19 severity;hence, the results could not be regarded as being fully adjusted. Besides, guiding glucocorticoid therapy based on serum cortisol levels is an impractical proposition, and to date is not backed by robust evidence. Therefore, routine measurement of serum cortisol in patients with COVID-19 is a futile endeavor and should not be encouraged. © Touch Medical Media 2020

Psychology of the students during, pre & post covid-19

This paper explains the need of understanding of the current situation of covid-19 pandemic in terms student’s point of view. The consent of this student’s perception is procured by a survey of teachers and students parallel during this covid-19 pandemic. By doing this, the paper identifies the fundamental values, institutions and pre-assumptions that the academia should challenge and break through to advance and reset the research and practice frontiers. The paper continues by discussing the major impacts, behaviors and experiences that three major stakeholders (namely students, teachers, programs and policy makers) are experiencing during three COVID-19. This provides an overview of the type and scale of the COVID-19 student impacts and implications for research.

Immuno-epidemiological model of two-stage epidemic growth

Epidemiological data on seasonal influenza show that the growth rate of the number of infected individuals can increase passing from one exponential growth rate to another one with a larger exponent. Such behavior is not described by conventional epidemiological models. In this work an immuno-epidemiological model is proposed in order to describe this two-stage growth. It takes into account that the growth in the number of infected individuals increases the initial viral load and provides a passage from the first stage of epidemic where only people with weak immune response are infected to the second stage where people with strong immune response are also infected. This scenario may be viewed as an increase of the effective number of susceptible increasing the effective growth rate of infected. © The authors. Published by EDP Sciences, 2020.