Identification of natural peptides from "PlantPepDB” database as anti-SARS-CoV-2 agents: A protein-protein docking approach

Background A global pandemic owing to COVID-19 infection has created havoc in the entire world. The etiological agent responsible for this viral outbreak is classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Still, there's no specific drug or preventive medication to treat SARS-CoV-2. This study was designed to demonstrate the efficacy of some anti-viral peptides obtained from a plant database i.e., PlantPepDB as potential ACE-2-Spike (S) protein complex neutralizers using a structure-based drug designing approach. Method A total of 83 anti-viral plant peptides were screened from a peptide database i.e. PlantPepDB based on their reported anti-viral activities against various viral strains. In order to screen peptides that may potentially interfere with ACE-2 and S complex formation, molecular docking studies were conducted using the flare module of Cresset software and subsequently, analysed the crucial interactions between the peptides and S complexes and ACE-2/S complex. Herein, the interactions and docking scores obtained for ACE-2/S complex were considered as references. The S-peptides complexes which displayed superior interactions and docking scores than reference complex i.e., ACE2-S were considered as final hits. The Molecular dynamics studies were conducted for a period of 30 ns for each of the final hit/S complex to understand the interaction stability and binding mechanism of designed peptides. Results The molecular docking results revealed that five peptides including Cycloviolacin Y3, Cycloviolacin Y1, White cloud bean defensin, Putative defensin 3.1, and Defensin D1 showed superior docking scores (i.e. -1372.5 kJ/mol to -1232.6 kJ/mol) when docked at the ACE2 binding site of S-protein than score obtained for the complex of ACE-2 and S protein i.e. -1183.4 kJ/mol. Moreover, these top five peptides manifested key interactions required to prevent the binding of S protein with ACE2. The molecular dynamics simulation study revealed that two of these five peptides i.e. Cycloviolacin Y3 and Cycloviolacin Y1 displayed minimal RMSD fluctuations. Conclusions The current structure-based drug-designing approach shows the possible role of anti-viral plant peptides as potential molecules to be explored at the initial stage of viral pathogenesis. Graphical Image, graphical

Network Analysis Guided Designing of Multi-Targeted Anti-Fungal Agents: Synthesis and Biological Evaluation.

During the ongoing pandemic, there have been increasing reports of invasive fungal disease (IFD), particularly among immunocompromised populations. Candida albicans is one of the most common clinical pathogenic microorganisms which have become a serious health threat to population either infected with Covid-19 or on treatment with immunosuppressant's/broad-range antibiotics. Currently, benzothiazole is a well explored scaffold for anti-fungal activity, especially mercapto substituted benzothiazoles. It is reported that exploring the 2nd position of benzothiazoles yield improved anti-fungal molecules. Therefore, in the current study, lead optimization approach using bioisosteric replacement protocol was followed to improve the anti-fungal activity of an already reported benzothiazole derivative, N-(1,3-benzothiazole-2-yl)-2-(pyridine-3-ylformohydrazido) acetamide. To rationally identify the putative anti-candida targets of this derivative, network analysis was carried out. Complexes of designed compounds and identified putative targets were further analyzed for the docking interactions and their consequent retention after the completion of exhaustive MD simulations. Top seven designed compounds were synthesized and evaluated for in-vitro anti-fungal property against Candida, which indicated that compounds 1.2c and 1.2f possess improved and comparable anti-fungal activity to N-(1,3-benzothiazole-2-yl)-2-(pyridine-3-ylformohydrazido) acetamide and Nystatin, respectively.

Analysing Research Trends in the Indian Hospitality and Tourism Sector: A Bibliometric Analysis for the Period 2000-2021

The purpose of the study was to have a better clarification of the popular themes studied by Indian researchers during the period 2000 to 2021. The paper helped in identifying the trends and development in research area in context to Indian Hospitality and tourism sector. The study selected a total of 1821 research papers of Indian origin from the scopus database during a span of 22 years (2000-2021). The selected publications were analyzed using different bibliometric methods of analysis using biblioshiny and VOS viewer within the scope of several parameters. The complete time period was divided into three distinct timeframes to study the research trends during the period. The maximum number of articles published in recent years, i.e. 2020, while minimum article publications in 2001. 1241 citations received in 2019 while only 110 citations received in 2005. 'Worldwide Hospitality and Tourism Themes' and 'International Journal of Contemporary Hospitality Management' were found to be the most productive journals. While ‘Singh S.’ is the most productive authors with a maximum number of articles, while 'Jauhari V' has the most number of citations for his work. Sustainability and conservation are the themes of common interest irrespective of timeframe, while the role of social media, covid 19 are recent trending topics for researchers. The study does contain certain limitations despite contributing significantly to the Hospitality and tourism literature in Indian context. The present study did not included publications other than articles like conferences proceedings, book chapters and dissertations etc. Selection of tools used and the keywords chosen for the study also limit the outcome. The findings of the analysis is helpful in better understanding the direction of research themes in the hotel and tourism industries. Evaluation of prominent authors and their work again helps on focusing the trending themes in the sector among researchers. Furthermore it helps future researchers in identifying key issues in the field of hospitality and tourism. The sample for this study, to the best of the authors' knowledge, was the most comprehensive collection of articles published in India's hospitality and tourism industries. This study adds substantially to the existing literature by highlighting current research orientations and trends in hospitality and tourism.

Managing Traumatic Brain Injury During the Coronavirus Disease 2019 Pandemic-A Case-Matched Controlled Analysis of Immediate Outcomes.

OBJECTIVE: The primary objective of this study was to evaluate the outcome of patients with traumatic brain injury (TBI) during the coronavirus disease 2019 (COVID-19) pandemic and to compare their outcome with case-matched controls from the prepandemic phase. METHODS: This is a retrospective case-control study in which all patients with TBI admitted during COVID-19 pandemic phase (Arm A) from March 24, 2020 to November 30, 2020 were matched with age and Glasgow Coma Scale score-matched controls from the patients admitted before March 2020 (Arm B). RESULTS: The total number of patients matched in each arm was 118. The length of hospital stay (8 days vs. 5 days; P < 0.001), transit time from emergency room to operation room (150 minutes vs. 97 minutes; P = 0.271), anesthesia induction time (75 minutes vs. 45 minutes; P = 0.002), and operative duration (275 minutes vs. 180 minutes; P = 0.002) were longer in arm A. Although the incidence of fever and pneumonia was significantly higher in arm A than in arm B (50% vs. 26.3%, P < 0.001 and 27.1% vs. 1.7%, P < 0.001, respectively), outcome (Glasgow Outcome Scale-Extended) and mortality (18.6% vs. 14.4% respectively; P = 0.42) were similar in both the groups. CONCLUSIONS: The outcome of the patients managed for TBI during the COVID-19 pandemic was similar to matched patients with TBI managed at our center before the onset of the COVID-19 pandemic. This finding suggests that the guidelines followed during the COVID-19 pandemic were effective in dealing with patients with TBI. This model can serve as a guide for any future pandemic waves for effective management of patients with TBI without compromising their outcome.

Is Fatty Liver Associated with Increased Mortality and Morbidity in Coronavirus Disease 2019 (COVID-19) Pneumonia?

Background: Fatty liver has been shown to be associated with severe COVID-19 disease without any impact on mortality. This is based on heterogenous criteria for defining both fatty liver as well as the severity parameters. This study aimed to study the impact of fatty liver on the mortality and severity of disease in patients with COVID-19 pneumonia. Methods: In a case control study design, patients with COVID-19 pneumonia (COVID-19 computed tomography severity index [CTSI] on high-resolution computed tomography chest of ≥1) with fatty liver (defined as liver to spleen attenuation index ≤5 on noncontrast computed tomography cuts of upper abdomen) were compared with those without fatty liver. The primary outcome measure was in-hospital mortality, and the secondary outcome measures were CTSI score, need for intensive care unit (ICU) care, need for ventilatory support, duration of ICU stay, and duration of hospital stay. Results: Of 446 patients with COVID-19 pneumonia, 289 (64.7%)admitted to Max Hospital, Saket, India, between January 1, 2021, and October 30, 2021, had fatty liver. Fifty-nine of 446 patients died during the index admission. In-hospital mortality was not different between patients with fatty liver (38 [13.24%]) or without fatty liver (21 [13.81%]). COVID-19 CTSI score was found to be significantly higher among patients who had fatty liver (13.40 [5.16] vs 11.81 [5.50]; P = 0.003). There was no difference in the requirement of ICU (94 [32%] vs 62 [39.49%]; P = 0.752), requirement of ventilatory support (27 [9.34%] vs 14 [8.91%]; P = 0.385), duration of ICU stay (8.29 [6.87] vs 7.07 [5.71] days; P = 0.208), and duration of hospital stay (10.10 [7.14] vs 10.69 [8.13] days; P = 0.430) between the groups with fatty liver or no fatty liver. Similarly, no difference was found in primary or secondary outcomes measure between the group with severe fatty liver vs mild/moderate or no fatty liver. High total leucocyte count and Fibrosis-4 (FIB-4) index were independently associated with mortality. Conclusions: Fatty liver may not be associated with increased mortality or clinical morbidity in patients who have COVID-19 pneumonia.

Effect of External Ventricular Drain Tunnel Length on Cerebrospinal Fluid Infection Rates-A Bayesian Network Meta-Analysis.

BACKGROUND: External ventricular drain (EVD)-associated cerebrospinal fluid infection (EACI) remains a major complication associated with EVD. Length of EVD tunnel, an overlooked but modifiable factor, can be associated with increased risk of EACI. The aim of this study is to find the tunnel length associated with least chances of EACI by performing a network meta-analysis. METHODS: A comprehensive search of different databases was performed to retrieve studies that studied the rates of EACI with different EVD tunnel lengths and a Bayesian network meta-analysis was performed. RESULTS: Six studies met the inclusion criteria and were included in the network meta-analysis. With 0 cm tunnel length as reference, the odds ratio (OR) for developing EACI was minimum for tunnel length 5-10 cm (OR, 0.027). It was followed by tunnel length of 5 cm (OR, 0.060) and 10 cm (OR, 0.075). The surface under the cumulative ranking curve plot showed that the probability of the tunnel length 5-10 cm (ranked first), 5 cm (ranked second), and 10 cm (ranked third) for being the best EVD tunnel length was found to be 86%, 64%, and 61%, respectively. CONCLUSIONS: The length for which an EVD is tunneled may have an impact on the rate of EACI. Our network meta-analyses showed that the tunnel length of 5-10 cm was associated with the lowest rates of EACI, with 86% probability of being the best EVD tunnel length. The probability of a patient with 5-10 cm EVD length developing EACI was 2.7% compared with zero tunnel length.

Investigating the role of electric vehicle knowledge in consumer adoption: evidence from an emerging market

Purpose>The use of electric vehicles has received popularity as alternative fuel vehicles to reduce greenhouse gas emissions and energy cost, which are expected to perform a crucial role in the near future of emerging mobility markets. The purpose of this empirical study is to analyse the role of electric vehicle knowledge in predicting consumer adoption intention directly and indirectly in the backdrop of an emerging market.Design/methodology/approach>The study approached an extended version of “Technology acceptance model” (TAM) based on the integrated framework of “knowledge-beliefs-intention”. The model was tested via direct and indirect path analyses with the data collected from Indian respondents using an online survey.Findings>The results indicate the robustness of the present research model, which shows that consumer adoption is significantly driven by electric vehicle knowledge, perceived usefulness, perceived ease of use and perceived risk. Electric vehicle knowledge has emerged as the most powerful cognitive measure, which directly affects the adoption intention along with the measures of “TAM”. Additionally, this also poses a higher indirect effect on adoption intention in the integrated model.Research limitations/implications>The study has focused on potential young and educated consumers, which may not be warranted to generalise the research findings, while youth or millennials are more receptive to adopt innovative and clean technology products like electric vehicle. Based on the findings, implications are offered for encouraging electric vehicles in the backdrop of emerging automobile markets.Originality/value>Concerning this cognitive phenomenon of knowledge, scant literature has been explored the role of subjective knowledge in consumer adoption for electric vehicles, particularly in the emerging markets like India. Thus, the present study analyses how consumers' knowledge about electric vehicle affects their decision to adopt this in the near future of Indian zero-emission mobility market.

Protein and peptide delivery to lungs by using advanced targeted drug delivery.

The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.

RdRp (RNA-dependent RNA polymerase): A key target providing anti-virals for the management of various viral diseases.

With the arrival of the Covid-19 pandemic, anti-viral agents have regained center stage in the arena of medicine. Out of the various drug targets involved in managing RNA-viral infections, the one that dominates almost all RNA viruses is RdRp (RNA-dependent RNA polymerase). RdRp are proteins that are involved in the replication of RNA-based viruses. Inhibition of RdRps has been an integral approach for managing various viral infections such as dengue, influenza, HCV (Hepatitis), BVDV, etc. Inhibition of the coronavirus RdRp is currently rigorously explored for the treatment of Covid-19 related complications. So, keeping in view the importance and current relevance of this drug target, we have discussed the importance of RdRp in developing anti-viral agents against various viral diseases. Different reported inhibitors have also been discussed, and emphasis has been laid on highlighting the inhibitor's pharmacophoric features and SAR profile.

Von Willebrand factor: A key glycoprotein involved in thrombo-inflammatory complications of COVID-19.

COVID-19 is an ongoing public health emergency that has affected millions of people worldwide and is still a threat to many more. One of the pathophysiological features of COVID-19 is associated with the activation of vascular endothelial cells (ECs) leading to the disruption of vascular integrity, coagulation and inflammation. An interlink mechanism between coagulation and inflammatory pathways has been reported in COVID-19. Multiple components are involved in these pathological pathways. Out of all, Von Willebrand Factor (VWF) is one of the primary components of coagulation pathway and also a mediator of vascular inflammation that plays an important role in thrombo-inflammation that further leads to acute respiratory distress syndrome (ARDS). The thrombo-inflammatory co-morbidities such as hyper-coagulation, thrombosis, ARDS etc. have become the major cause of mortality in the patients of COVID-19 admitted to the ICU. Thus, VWF can be explored as a potential target to manage COVID-19 associated co-morbidities. Supporting this hypothesis, there are literature reports which disclose previous attempts to target VWF for the management of thrombo-inflammation in other pathological conditions. The current report summarizes emerging insights into the pathophysiology, mechanism(s), diagnosis, management and foundations for research on this less explored clinically relevant glycoprotein as coagulation biomarker in COVID-19.

A survey based on oral complications in COVID recovered patients: a questionnaire based original research study

Background: The world face an unprecedented situation in Health services due to global COVID-19 outbreak. COVID-19 therapies and multi-drug treatment have some indirect complexities, COVID-19 disease aggravate some oral complications, particularly those with autoimmune diseases, people with compromised immune system or are on long-term pharmacotherapy. Methodology: A total of 432 Covid recovered patients were selected from last 5 months. A questionnaire survey and patient interview was done to determine the suitability of subjects for the study.

Coronavirus Disease 2019: A Brief Review of the Clinical Manifestations and Pathogenesis to the Novel Management Approaches and Treatments.

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) in China, which spread to the rest of the world, led the World Health Organization to classify it as a global pandemic. COVID-19 belongs to the Bettacoronavirus genus of the Coronaviridae family, and it mainly spreads through the respiratory tract. Studies have now confirmed a human-to-human transmission as the primary pathway of spread. COVID-19 patients with a history of diseases such as respiratory system diseases, immune deficiency, diabetes, cardiovascular disease, and cancer are prone to adverse events (admission to the intensive care unit requiring invasive ventilation or even death). The current focus has been on the development of novel therapeutics, including antivirals, monoclonal antibodies, and vaccines. However, although there is undoubtedly an urgent need to identify effective treatment options against infection with COVID-19, it is equally important to clarify management protocols for the other significant diseases from which these patients may suffer, including cancer. This review summarizes the current evidence regarding the epidemiology, pathogenesis, and management of patients with COVID-19. It also aims to provide the reader with insights into COVID-19 in pregnant patients and those with cancer, outlining necessary precautions relevant to cancer patients. Finally, we provide the available evidence on the latest potent antiviral drugs and vaccines of COVID-19 and the ongoing drug trials.

Underscoring the immense potential of chitosan in fighting a wide spectrum of viruses: A plausible molecule against SARS-CoV-2?

Chitosan is a deacetylated polycationic polysaccharide derived from chitin. It is structurally constituted of N-acetyl-D-glucosamine and ß-(1-4)-linked D-glucosamine where acetyl groups are randomly distributed across the polymer. The parameters of deacetylation and depolymerization process greatly influence various physico-chemical properties of chitosan and thus, offer a great degree of manipulation to synthesize chitosan of interest for various industrial and biomedical applications. Chitosan and its various derivatives have been a potential molecule of investigation in the area of anti-microbials especially anti-fungal, anti-bacterial and antiviral. The current review predominantly highlights and discusses about the antiviral activities of chitosan and its various substituted derivatives against a wide spectrum of human, animal, plants and bacteriophage viruses. The extrinsic and intrinsic factors that affect antiviral efficacy of chitosan have also been talked about. With the rapid unfolding of COVID-19 pandemic across the globe, we look for chitosan as a plausible potent antiviral molecule for fighting this disease. Through this review, we present enough literature data supporting role of chitosan against different strains of SARS viruses and also chitosan targeting CD147 receptors, a novel route for invasion of SARS-CoV-2 into host cells. We speculate the possibility of using chitosan as potential molecule against SARS-CoV-2 virus.

Viral Ribonucleic Acid Shedding and Transmission Potential of Asymptomatic and Paucisymptomatic Coronavirus Disease 2019 Patients.

We studied the pattern and duration of viral ribonucleic acid (RNA) shedding in 32 asymptomatic and 11 paucisymptomatic coronavirus disease 2019 cases. Viral RNA shedding in exhaled breath progressively diminished and became negative after 6 days of a positive reverse-transcription polymerase chain reaction test. Therefore, the duration of isolation can be minimized to 6 days.

[Development and implementation of an operational concept in a university eye hospital in the SARS-CoV-2 pandemic]. / Entwicklung und Implementierung eines Betriebskonzeptes in einer Universitätsaugenklinik im Rahmen der SARS-CoV-2-Pandemie.

The SARS-CoV­2 pandemic poses major challenges for the entire medical care system. Especially in maximum care clinical facilities, a higher exposure to potentially infectious patients or positively tested COVID-19 patients is to be expected. A hospital facility concept was developed in the Department of Ophthalmology, Goethe University, Frankfurt am Main, Germany with the aim of achieving maximum patient safety with maximum employee protection. The current infection control hygiene recommendations of the Robert Koch Institute (RKI), the leading specialist association, were taken into consideration along with the existing hospital hygiene plan of the University Hospital Frankfurt am Main. Incorporated into the developmental process were the Institute for Medical Microbiology and Hospital Hygiene, the occupational medical service department and the board of the University Hospital Frankfurt am Main. The operational concept with individualized measures ensures that (i) the care of outpatients; (ii) the performance of outpatient operations; (iii) and the care of admitted patients and patients undergoing surgery are also guaranteed during the COVID-19 pandemic. All measures have been documented in writing in the clinic's internal quality manual and are thus accessible to all employees. The concept is regularly checked for functionality, so-called stress tests and hygiene inspections are carried out and improvements are made as necessary.