Phytochemicals of Withania somnifera as a Future Promising Drug against SARS-CoV-2: Pharmacological Role, Molecular Mechanism, Molecular Docking Evaluation, and Efficient Delivery.

Coronavirus disease (COVID-19) has killed millions of people since first reported in Wuhan, China, in December 2019. Intriguingly, Withania somnifera (WS) has shown promising antiviral effects against numerous viral infections, including SARS-CoV and SARS-CoV-2, which are contributed by its phytochemicals. This review focused on the updated testing of therapeutic efficacy and associated molecular mechanisms of WS extracts and their phytochemicals against SARS-CoV-2 infection in preclinical and clinical studies with the aim to develop a long-term solution against COVID-19. It also deciphered the current use of the in silico molecular docking approach in developing potential inhibitors from WS targeting SARS-CoV-2 and host cell receptors that may aid the development of targeted therapy against SARS-CoV-2 ranging from prior to viral entry until acute respiratory distress syndrome (ARDS). This review also discussed nanoformulations or nanocarriers in achieving effective WS delivery to enhance its bioavailability and therapeutic efficacy, consequently preventing the emergence of drug resistance, and eventually therapeutic failure.

Epidemiological Factors of Periodontal Disease Among South Indian Adults.

Introduction: Oral conditions exist worldwide, and are related with astounding morbidity. Indian adults' incidence of mild and moderate periodontal conditions was nearly 25%, while about 19% of adults experience severe periodontitis. Objective: The aim of this study was to analyse epidemiological factors of periodontal disease among a south Indian population based on the role of sociodemographic factors, habitual factors and set of oral health knowledge, attitude, and behaviour measures. Methods: A sample of 288 participants above 18 years of age residing in Tamil Nadu, India took part in this cross-sectional study. Based on WHO criteria, periodontal disease was measured in our study. Age, ethnicity, smoking, education, and oral health behavior were found to be the covariates. Ordinal logistic regression analysis using R version 3.6.1 was utilized to study the various factors that influence periodontal disease among south Indian adults. Results: Various demographic factors such as age between 25 and 34 years (AOR = 2.25; 95% CI 1.14-4.55), 35-44 years (AOR = 1.80; 95% CI 0.89-3.64), ≥ 45 years old (AOR = 2.89; 95% CI 1.41-6.01), ethnicity (AOR = 2.71; 95% CI 1.25-5.81), smoking (AOR = 0.38; 95% CI 0.16-0.65), primary level education (AOR = 0.07; 95% CI 0.01-0.50) high school level education (AOR = 0.06; 95% CI 0.01-0.27), university level education (AOR = 0.08; 95% CI 0.01-0.36) and an individual's oral health behavior (AOR = 0.59; 95% CI 0.32-1.08) were found to be related with periodontal disease among the south Indian population. The maximum log likelihood residual deviance value was 645.94 in the final model. Conclusion: Based on our epidemiological findings, sociodemographic, habitual factors and oral health behavior play a vital role in an individual's periodontal status among south Indian adults. An epidemiological model derived from the factors from our study will help to bring better understanding of the disease and to implement various preventive strategies to eliminate the causative factors.

COVID-19 Biomedical Plastics Wastes—Challenges and Strategies for Curbing the Environmental Disaster

The rise of the COVID-19 outbreak has made handling plastic waste much more difficult. Our superior, hyper-hygienic way of life has changed our behavioural patterns, such as the use of PPE (Personal Protective Equipment), the increased desire for plastic-packaged food and commodities, and the use of disposable utensils, as a result of the fear of transmission. The constraints and inefficiencies of our current waste management system, in dealing with our growing reliance on plastic, could worsen its mismanagement and leakage into the environment, causing a new environmental crisis. A sustainable, systemic, and hierarchical plastic management plan, which clearly outlines the respective responsibilities as well as the socioeconomic and environmental implications of these actions, is required to tackle the problem of plastic pollution. It will necessitate action strategies tailored to individual types of plastic waste and country demand, as well as increased support from policymakers and the general public. The situation of biomedical plastic wastes during the COVID-19 epidemic is alarming. In addition, treatment of plastic waste, sterilisation, incineration, and alternative technologies for transforming bio-plastic waste into value-added products were discussed, elaborately. Our review would help to promote sustainable technologies to manage plastic waste, which can only be achieved with a change in behaviour among individuals and society, which might help to safeguard against going from one disaster to another in the coming days.

A European pharmacotherapeutic agent roflumilast exploring integrated preclinical and clinical evidence for SARS CoV-2 mediated inflammation to organ damage.

COVID-19 has spread globally, affecting almost 160 million individuals. Elderly and pre-existing patients (such as diabetes, heart disease and asthma) seem more susceptible to severe illness with COVID-19. Roflumilast was licensed for usage in the European Union in July 2010 as a phosphodiesterase-4 (PDE4) inhibitor. Under preclinical studies, roflumilast has been shown to decrease bleomycin-induced lung fibrosis, lung hydroxyproline and right heart thickening. The current study reviewed existing data that the PDE-4 inhibitor, a roflumilast, protects renal tissues and other major organ systems after COVID-19 infection by decreasing immune cell infiltration. These immune-balancing effects of roflumilast were related to a decrease in oxidative and inflammatory burden, caspase-3 suppression and increased protein kinase A (PKA)/cyclic A.M.P. (cAMP) levels in renal and other organ tissue.

Potential of Marine Terpenoids against SARS-CoV-2: An In Silico Drug Development Approach.

In an emergency, drug repurposing is the best alternative option against newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, several bioactive natural products have shown potential against SARS-CoV-2 in recent studies. The present study selected sixty-eight broad-spectrum antiviral marine terpenoids and performed molecular docking against two novel SARS-CoV-2 enzymes (main protease or Mpro or 3CLpro) and RNA-dependent RNA polymerase (RdRp). In addition, the present study analysed the physiochemical-toxicity-pharmacokinetic profile, structural activity relationship, and phylogenetic tree with various computational tools to select the 'lead' candidate. The genomic diversity study with multiple sequence analyses and phylogenetic tree confirmed that the newly emerged SARS-CoV-2 strain was up to 96% structurally similar to existing CoV-strains. Furthermore, the anti-SARS-CoV-2 potency based on a protein-ligand docking score (kcal/mol) exposed that the marine terpenoid brevione F (-8.4) and stachyflin (-8.4) exhibited similar activity with the reference antiviral drugs lopinavir (-8.4) and darunavir (-7.5) against the target SARS-CoV-Mpro. Similarly, marine terpenoids such as xiamycin (-9.3), thyrsiferol (-9.2), liouvilloside B (-8.9), liouvilloside A (-8.8), and stachyflin (-8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (-7.4), and favipiravir (-5.7) against the target SARS-CoV-2-RdRp. The above in silico investigations concluded that stachyflin is the most 'lead' candidate with the most potential against SARS-CoV-2. Previously, stachyflin also exhibited potential activity against HSV-1 and CoV-A59 within IC50, 0.16-0.82 µM. Therefore, some additional pharmacological studies are needed to develop 'stachyflin' as a drug against SARS-CoV-2.

Disruption of the biological activity of protease-activated receptors2/4 in adults rather than children in SARS CoV-2 virus-mediated mortality in COVID-19 infection.

One of the most remarkable results in 2019 is the reduced prevalence and death of children from coronavirus infection (COVID-19). In 2019, a worldwide pandemic impacted around 0.1 billion individuals, with over 3.5 million mortality reported in the literature. There is minimal knowledge on SARS-CoV-2 infection immunological responses in kids. Studies have been focused mostly on adults and children since the course of pediatric sickness is often short. In adults, severe COVID-19 is related to an excessive inflammatory reaction. Macrophages and monocytes are well known to contribute to this systemic response, although numerous lines are indicative of the importance of neutrophils. An increased number of neutrophils and neutrophil to lymphocyte ratios are early signs of SARS-CoV-2 and a worse prognosis. In this study that it is crucial to monitor PAR2 and PAR4 expression and function (since nursing children have elevated levels) and the inhibiting the normal physiology through the use of anticoagulants may exacerbate the problem in adults. Thus, in COVID-19 infection, we propose the use of antiplatelet (thromboxane A2 inhibitors), if required rather than anticoagulants (FXa and thrombin Inhibitors).

Impact of COVID-19 in public health: Prevalence and preventive approaches.

The outbreak of CoVID-19 infection rapidly increases worldwide. Most of the continents affecting from CoVID-19 and still widening its burden disease (Jones DS, 2020; Lai et al., 2020). Along with its fatality rates, CoVID-19 has caused physiological disturbances in the society and termed as "coronophobia". CoVID-19 with renal failure, severe pneumonia and respiratory syndrome patients have been reported to increase the severity of disease conditions (Sevim et al., 2020). Also, CoVID-19 with cancer patients increase the higher risk of infections. Currently, there is no vaccine or specific treatment against CoVID-19 and drug research centres continuously investigating the potential drug against CoVID-19 (Osama and Amer, 2020). For the past 20 years two major coronavirus epidemics have occurred in public includes SARS-CoV approximately 8000 cases and 800 deaths and MERS-CoV 2,500 cases and 800 deaths and these continuing sporadically (Cascella et al., 2020).