Long-acting vaccine delivery systems.

Bolus vaccines are often administered multiple times due to rapid clearance and reduced transportation to draining lymph nodes resulting in inadequate activation of T and B lymphocytes. In order to achieve adaptive immunity, prolonged exposure of antigens to these immune cells is crucial. Recent research has been focusing on developing long-acting biomaterial-based vaccine delivery systems, which can modulate the release of encapsulated antigens or epitopes to facilitate enhanced antigen presentation in lymph nodes and subsequently achieve robust T and B cell responses. Over the past few years, various polymers and lipids have been extensively explored to develop effective biomaterial-based vaccine strategies. The article reviews relevant polymer and lipid-based strategies used to prepare long-acting vaccine carriers and discusses their results concerning immune responses.

Potential medicinal plants to combat viral infections: A way forward to environmental biotechnology.

The viral diseases encouraged scientific community to evaluate the natural antiviral bioactive components rather than protease inhibitors, harmful organic molecules or nucleic acid analogues. For this purpose, medicinal plants have been gaining tremendous importance in the field of attenuating the various kinds of infectious and non-infectious diseases. Most of the commonly used medicines contains the bioactive components/phytoconstituents that are generally extracted from medicinal plants. Moreover, the medicinal plants offer many advantages for the recovery applications of infectious disease especially in viral infections including HIV-1, HIV-2, Enterovirus, Japanese Encephalitis Virus, Hepatitis B virus, Herpes Virus, Respiratory syncytial virus, Chandipura virus and Influenza A/H1N1. Considering the lack of acceptable drug candidates and the growing antimicrobial resistance to existing drug molecules for many emerging viral diseases, medicinal plants may offer best platform to develop sustainable/efficient/economic alternatives against viral infections. In this regard, for exploring and analyzing large volume of scientific data, bibliometric analysis was done using VOS Viewer shedding light on the emerging areas in the field of medicinal plants and their antiviral activity. This review covers most of the plant species that have some novel bioactive compound like gnidicin, gniditrin, rutin, apigenin, quercetin, kaempferol, curcumin, tannin and oleuropin which showed high efficacy to inhibit the several disease causing virus and their mechanism of action in HIV, Covid-19, HBV and RSV were discussed. Moreover, it also delves the in-depth mechanism of medicinal with challenges and future prospective. Therefore, this work delves the key role of environment in the biological field.

A review on synthesis of antiviral drugs, in silico studies and their toxicity

Viruses have been around us for a long period of time, they affect humans, animals and plant on cellular level by using host's body to dwell and reproduce. The spread of HIV was reported in 1981 and created a global threat to public health. In the areas of basic virology, immunology and pathogenesis of HIV/AIDS, the development of antiretroviral medicines and significant progress has been made in recent years. Majority of these antiviral compounds have the potential to be used as HIV drugs, however they are frequently accompanied with some side effects. With the emergence of the COVID-19, human race is facing a new public health crisis and repurposing of antiviral drugs to block the function of Mpro of the new corona virus has been started. This review covers the information related to the synthesis of various types of antiviral drugs and their toxicity. Some of these are used as repurposing drugs to cure patients suffering from other diseases, therefore, information for in Silico studies of antiviral drugs is incorporated. In brief, this review focused on different types of antiviral drugs, their synthesis, their repurposing role and the toxicity.

Exploration of Potent Antiviral Phytomedicines from Lauraceae Family Plants against SARS-CoV-2 Main Protease.

A new Coronaviridae strain, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), emerged from Wuhan city of China and caused one of the substantial global health calamities in December 2019. Even though several vaccines and drugs have been developed worldwide since COVID-19, a cost-effective drug with the least side effects is still unavailable. Currently, plant-derived compounds are mostly preferred to develop antiviral therapeutics due to its less toxicity, easy access, and cost-effective characteristics. Therefore, in this study, 124 phytochemical compounds from plants of Lauraceae family with medicinal properties were virtually screened against SARS-CoV-2 Mpro. Identification of four phytomolecules, i.e., cassameridine, laetanine, litseferine and cassythicine, with docking scores -9.3, -8.8, -8.6, and -8.6 kcal/mol, respectively, were undertaken by virtual screening, and molecular docking. Furthermore, the molecular dynamic simulation and essential dynamics analysis have contributed in understanding the stability and inhibitory effect of these selected compounds. These phytomolecules can be considered for further in vitro and in vivo experimental study to develop anti-SARS-CoV-2 therapeutics targeting the main protease (Mpro).

Health Risk Appraisal Associated with Air Quality over Coal-Fired Thermal Power Plants and Coalmine Complex Belts of Urban-Rural Agglomeration in the Eastern Coastal State of Odisha, India

Manufacturing and mining sectors are serious pollution sources and risk factors that threaten air quality and human health. We analyzed pollutants at two study sites (Talcher and Brajrajnagar) in Odisha, an area exposed to industrial emissions, in the pre-COVID-19 year (2019) and consecutive pandemic years, including lockdowns (2020 and 2021). We observed that the annual data for pollutant concentration increased at Talcher: PM2.5 (7-10%), CO (29-35%), NO2 and NOx (8-57% at Talcher and 14-19% at Brajrajnagar);while there was slight to substantial increase in PM10 (up to 11%) and a significant increase in O3 (41-88%) at both sites. At Brajrajnagar, there was a decrease in PM2.5 (up to 15%) and CO (around half of pre-lockdown), and a decrease in SO2 concentration was observed (30-86%) at both sites. Substantial premature mortality was recorded, which can be attributed to PM2.5 (16-26%), PM10 (31-43%), NO2 (15-21%), SO2 (4-7%), and O3 (3-6%). This premature mortality caused an economic loss between 86-36 million USD to society. We found that although lockdown periods mitigated the losses, the balance of rest of the year was worse than in 2019. These findings are benchmarks to manage air quality over Asia's largest coalmine fields and similar landscapes.

Air Crash Investigation: Pattern of Spinal Injuries, Management During the COVID-19 Pandemic, and Outcomes.

BACKGROUND: Spinal injuries following an air crash can be fatal, and recognizing the patients who need immediate attention and early management could save those patients from ending up with lifelong disabilities and other consequences. However, taking appropriate actions in a pandemic situation presents additional challenges. We present our report of air crash victims with spinal injuries, along with their patterns, morphology, management, and outcomes during the COVID-19 pandemic. METHODS: An analysis was performed on the spinal injuries of victims of the Boeing 737 crash landing at the Karipur Airport (Calicut International Airport, Kerala, India) who were treated at a tertiary care referral hospital in August 2020. Details of the initial triage, patterns of injury, morphologies, mechanisms, management principles, and outcomes at 9 months postinjury were recorded and analyzed. RESULTS: Of the 47 patients received at our center, 44 survivors were triaged and 13 patients (29.5%) were identified to have spinal injuries of varying severities. The majority of the injuries were chance fractures at the lumbar level, followed by burst and compression fractures. A total of 6 patients underwent surgery, following all COVID-19 guidelines based on priority. All survivors had positive outcomes with our management. No complications such as secondary infections, worsening of neurological deficits, or implant failures were recorded. CONCLUSION: A high incidence of spinal injuries is seen in air crash victims. Early prioritized surgical management in selected patients provides excellent outcomes. Disaster management during a pandemic situation is a difficult task, where proper planning and execution is necessary to provide optimal results.

Vitamin D in defense against the terrorism of coronavirus disease 2019: A meta-analysis

Background: Coronavirus disease 2019 (COVID-19) pandemic was also spread during winter time in December from Wuhan the city of China to worldwide. Various studies conducted throughout the world have indicated the possible relationship between Vitamin D and COVID-19 infection. Aim: This narrative review is designed to support Vitamin D role and its efficacy in managing COVID-19 menace. Materials and Methods: Latest 50 articles for Vitamin D, and COVID-19 relationship and management were scrutinized to summarize this article from data bases of PubMed and Google scholar in English language. Diagrams were created by biorender.com to summarize pictorial relations. Conclusions: Higher mortality is associated with countries of high-level Vitamin D deficiencies. Many studies have found a significant relation between Vitamin D deficiency and COVID-19 complications and related comorbidities. It is highly supported by many literature to recommend daily dose of Vitamin D3 10,000 IU/day for a few weeks to rapidly increase 25-hydroxyvitamin D levels above 40–60 ng/mL, in population at higher risk.

Current insights and molecular docking studies of the drugs under clinical trial as rdrp inhibitors in COVID-19 treatment.

Study background & Objective: After the influenza pandemic (1918), COVID-19 was declared a Vth pandemic by the WHO in 2020. SARS-CoV-2 is an RNA-enveloped single-stranded virus. Based on the structure and life cycle, Protease (3CLpro), rdrp, ACE2, IL-6, and TMPRSS2 are the major targets for drug development against COVID-19. Pre-existing several drugs (FDA-approved) are used to inhibit the above targets in different diseases. In coronavirus treatment, these drugs are also in different clinical trial stages. Remdesivir (rdrp inhibitor) is the only FDA-approved medicine for coronavirus treatment. In the present study, by using the drug repurposing strategy, 70 preexisting clinical or under clinical trial molecules were used in scrutiny for rdrp inhibitor potent molecules in coronavirus treatment being surveyed via docking studies. Molecular simulation studies further confirmed the binding mechanism and stability of the most potent compounds. MATERIAL AND METHODS: Docking studies were performed using the Maestro 12.9 module of Schrodinger software over 70 molecules with rdrp as the target and remdesivir as the standard drug and further confirmed by simulation studies. RESULTS: The docking studies showed that many HIV protease inhibitors demonstrated remarkable binding interactions with the target rdrp. Protease inhibitors such as lopinavir and ritonavir are effective. Along with these, AT-527, ledipasvir, bicalutamide, and cobicistat showed improved docking scores. RMSD and RMSF were further analyzed for potent ledipasvir and ritonavir by simulation studies and were identified as potential candidates for corona disease. CONCLUSION: The drug repurposing approach provides a new avenue in COVID-19 treatment.

Vaccine hesitancy for coronavirus SARS-CoV-2 in Varanasi India

With the rollout of the world's largest vaccine drive for SARS-CoV-2 by the Government of India on January 16 2021, India had targeted to vaccinate its entire population by the end of 2021. Struggling with vaccine procurement and production earlier, India overcome these hurdles, but the Indian population still did not seem to be mobilizing swiftly toward vaccination centers. The severe second wave has slowed the vaccination pace and was also one of the major contributing factors to vaccine hesitancy. To understand the nature of vaccine hesitancy and its underlying factors, we conducted extensive online and offline surveys in Varanasi and adjoining regions using structured questions. Most respondents were students (0.633). However, respondents from other occupations, such as government officials (0.10), have also participated in the study. Interestingly, most people (0.75) relied on fake news and did not take COVID-19 seriously. Most importantly, we noticed that a substantial proportion of respondents (relative frequency 0.151;mean age 24.8 years) reported that they were still not interested in vaccination. We observed a significant association between vaccine hesitancy and socioeconomic status (χ2 = 307.6, p < 0.001). However, we failed to detect any association between vaccine hesitancy and gender (χ2 = 0.007, p > 0.5). People who have neither been vaccinated nor have ever been infected may become the medium for spreading the virus and creating new variants, which may lead to the vaccine-resistant variant. We expect this extensive survey to help the Government upgrade their vaccination policies for COVID-19 in North India.

Thermal degradation of hazardous 3-layered COVID-19 face mask through pyrolysis: Kinetic, thermodynamic, prediction modelling using ANN and volatile product characterization.

Nowadays, wearing a 3-layered face mask (3LFM) to protect against coronavirus illness (COVID-19) has become commonplace, resulting in massive, hazardous solid waste. Since most of them are infected with viruses, a secure way of disposal is necessary to prevent further virus spread. Pyrolysis treatment has recently developed as an effective method for disposing of such hazardous waste and consequently converting them into energy products. In this regard, the goal of the present study is to physicochemically characterize the 3LFM followed by pyrolysis in a TGA to evaluate the pyrolysis performance, kinetic, and thermodynamic parameters and in a semi-batch reactor to characterize the volatile product. Furthermore, an artificial neural network (ANN) was used to forecast thermal deterioration data. The results demonstrated a strong correlation between real and anticipated values. The study proved the relevance of the ANN model and the applicability of pyrolysis for disposing of 3LFM while simultaneously producing energy products.

The Post-Vaccination Quantitative Total Immunoglobulin Levels against SARS-CoV-2 in Healthcare Workers: A Multi-Centric Cohort Study in India.

Healthcare workers (HCWs) in India received the AZD1222 and BBV152 vaccines from January 2021 onwards. The objective of this study was to compare the immune response (seropositivity rate and geometric mean titer (GMT), and 95% confidence interval (CI)] against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in HCWs who received these vaccines, after the first and second doses. Therefore, the total immunoglobulin (Ig) levels specific to SARS-CoV-2 were measured using quantitative enzyme-linked immunosorbent assay (ELISA). The study population of 133 HCWs consisted of two groups in which the immune response was measured for the AZD1222 and BBV152 vaccines. Data collection was performed from 6 February to 20 August 2021. Four weeks after the first and second dose, the odds ratio of seroconversion for AZD1222 and BBV152 vaccine was 10.3 times (95% CI: 4.5-23.7) and 15.9 times (95% CI: 6.3-39.9), respectively. The GMT was 6392.93 and 6398.82 U/mL for AZD1222 and 1480.47 and 990.38 U/mL for BBV152 after the first and second doses, respectively. Both vaccines elicited an immune response, but the seroconversion rate and GMT after each dose were significantly higher for AZD1222 than those for the BBV152 vaccine in this study.

Immunomodulator Vitamin C: An Adjuvant Therapy in Second Wave of Coronavirus Disease 2019

Since its sudden outbreak in December 2019 in Wuhan, A pandemic of SARS-CoV-2 has been announced. Vitamin C is a water-soluble vitamin with anti-oxidant and immunity-boosting properties. Vitamin C acts as a nutritional supplement profoundly impacting the immune response to the second or third wave of the coronavirus disease (COVID-19). Vitamin C efficacy as an adjuvant treatment for inflammation and symptoms associated with COVID-19 infection should be investigated further. This report sheds light on the available information on the current clinical trials and pharmacotherapy related to COVID-19. Information available on Pubmed, EMBASE, Scopus, Web of Science databases and EU clinical trials regarding the use of therapeutic agents in patients with COVID-19 was used to perform analysis. Data was taken from 18 clinical trials available in the U.S. National Library of Medicine. All trials that are active, completed, or in the process of recruiting are included in data. Because of majority of clinical trials are still ongoing, specific results and high-quality clinical evidence are lacking. Before being standardised for use, the protocol must undergo large randomised clinical studies using a variety of existing medications and potential therapies. The pivotal role played by vitamins C in maintaining our immune system, is quite apparent. This review is an attempt to summarize the available information regarding the use of vitamin C as an adjuvant therapy in COVID-19 patients.

An Insight to Heat Shock Protein 90: A Remedy for Multiple Problems.

Heat shock protein 90 (Hsp90) is a chaperone protein that prevents many other proteins from aggregating by folding them in a certain way. Hsp90 consists of three structural domains: N-terminal, middle and C-terminal domains. Hsp90 has many activities in numerous proteins and signaling pathways like chimeric fusion proteins, steroid hormone receptors, tumor suppressor genes, and cell cycle regulatory proteins. The role of Hsp90 is not only in cancer but also in other diseases like COVID-19, leishmaniasis, diabetes, flavi virus, systemic sclerosis, grass carp reovirus, psoriasis, malaria, cardiac fibrosis, and alcohol-related liver diseases. This review is a compilation of the pharmacological profile of Hsp90 inhibitors, problems associated with them, and suggested remedies for the same.

COVID-19 infection in patients with haematological disease - A tertiary centre experience from north India.

This retrospective study was aimed to understand the clinical, laboratory, radiological parameters and the outcome of COVID-19 patients with underlying haematological disease. All patients with known haematological disease admitted with COVID-19-positive status from April to August 2020 in the COVID-19 facility of a tertiary care centre in north India, were included. Their medical records were analyzed for outcome and mortality risk factors. Fifty four patients, 37 males, were included in the study. Of these, 36 patients had haematological malignancy and 18 had benign disorder. Fever (95.5%), cough (59.2%) and dyspnoea (31.4%) were the most common symptoms. Nine patients had severe disease at diagnosis, mostly malignant disorders. Overall mortality rate was 37.0 per cent, with high mortality seen in patients with aplastic anaemia (50.0%), acute myeloid (46.7%) and lymphoblastic leukaemia (40.0%). On univariate analysis, Eastern Cooperative Oncology Group performance status >2 [odd ratio (OR) 11.6], COVID-19 severity (OR 8.2), dyspnoea (OR 5.7) and blood product transfusion (OR 6.4) were the predictors of mortality. However, the presence of moderate or severe COVID-19 (OR 16.6, confidence interval 3.8-72.8) was found significant on multivariate analysis. The results showed that patients with haematological malignancies and aplastic anaemia might be at increased risk of getting severe COVID-19 infection and mortality as compared to the general population.

Rural-urban differentials in the prevalence of diarrhoea among older adults in India: Evidence from Longitudinal Ageing Study in India, 2017-18.

INTRODUCTION: Diarrhoeal diseases are common among children and older adults. Yet, majority of the scientific studies deal with children, neglecting the other vulnerable and growing proportion of the population-the older adults. Therefore, the present study aims to find rural-urban differentials in the prevalence of diarrhoea among older adults in India and its states. Additionally, the study aims to find the correlates of diarrhoea among older adults in India. The study hypothesizes that there are no differences in the prevalence of diarrhoea in rural and urban areas. METHODS: Data for this study was utilized from the recent Longitudinal Ageing Study in India (2017-18). The present study included eligible respondents aged 60 years and above (N = 31,464). Descriptive statistics along with bivariate analysis was presented to reveal the preliminary results. In addition, binary logistic regression analysis was used to fulfil the study objectives. RESULTS: About 15% of older adults reported that they suffered from diarrhoea in the last two years. The prevalence of diarrhoea among older adults was found to be highest in Mizoram (33.5 per cent), followed by Chhattisgarh (30.7 per cent) and Bihar (30.2 per cent). There were significant rural-urban differences in the prevalence of diarrhoea among older adults in India (difference: 7.7 per cent). The highest rural-urban differences in the prevalence of diarrhoea were observed among older adults who were 80+ years old (difference: 13.6 per cent), used unimproved toilet facilities (difference: 12.7 per cent), lived in the kutcha house (difference: 10.2 per cent), and those who used unclean source of cooking fuel (difference: 9 per cent). Multivariate results show that the likelihood of diarrhoea was 17 per cent more among older adults who were 80+ years compared to those who belonged to 60-69 years' age group [AOR: 1.17; CI: 1.04-1.32]. Similarly, the older female had higher odds of diarrhoea than their male counterparts [AOR: 1.19; CI: 1.09-1.30]. The risk of diarrhoea had declined with the increase in the educational level of older adults. The likelihood of diarrhoea was significantly 32 per cent more among older adults who used unimproved toilet facilities than those who used improved toilet facilities [AOR: 1.32; CI: 1.21-1.45]. Similarly, older adults who used unimproved drinking water sources had higher odds of diarrhoea than their counterparts [AOR: 1.45; CI: 1.25-1.69]. Moreover, older adults who belonged to urban areas were 22 per cent less likely to suffer from diarrhoea compared to those who belonged to rural areas [AOR: 0.88; CI: 0.80-0.96]. CONCLUSION: The findings of this study reveal that diarrhoea is a major health problem among older adults in India. There is an immediate need to address this public health concern by raising awareness about poor sanitation and unhygienic practices. With the support of the findings of the present study, policy makers can design interventions for reducing the massive burden of diarrhoea among older adults in rural India.

Nanobiotics against antimicrobial resistance: harnessing the power of nanoscale materials and technologies.

Given the spasmodic increment in antimicrobial resistance (AMR), world is on the verge of "post-antibiotic era". It is anticipated that current SARS-CoV2 pandemic would worsen the situation in future, mainly due to the lack of new/next generation of antimicrobials. In this context, nanoscale materials with antimicrobial potential have a great promise to treat deadly pathogens. These functional materials are uniquely positioned to effectively interfere with the bacterial systems and augment biofilm penetration. Most importantly, the core substance, surface chemistry, shape, and size of nanomaterials define their efficacy while avoiding the development of AMR. Here, we review the mechanisms of AMR and emerging applications of nanoscale functional materials as an excellent substitute for conventional antibiotics. We discuss the potential, promises, challenges and prospects of nanobiotics to combat AMR.

Multiple ligation-Assisted recombinase polymerase amplification for highly sensitive and selective colorimetric detection of SARS-CoV-2.

In this paper we present a new method for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), targeting a specific region "N gene." Under isothermal reaction conditions, we integrated ligation (Lig; high selectivity) and recombinase polymerase amplification (RPA; high sensitivity) processes, obtaining a robust method of detection. For point-of-care testing, we incorporated our laboratory-produced pyrophosphate ion (PPi)-sensing probe (PK-probe) for colorimetric analysis of the reaction. The total detection system was efficient and effective at diagnosing this RNA virus-mediated disease rapidly (30 min). In a full-genome SARS-CoV-2 study, our PK-probe/Lig-RPA system functioned with a limit of detection of 1160 copies/ml, with a single-mismatch level of selectively, and it was highly selective even in the presence of bacterial genomes commonly found in the human mouth and nose. This robust, straightforward, selective, efficient, and ultrasensitive colorimetric detection method, with potential for point-of-care analysis, should also be effective in detecting a diverse range of other RNA-based diseases.

Integrated COVID-19 Predictor: Differential expression analysis to reveal potential biomarkers and prediction of coronavirus using RNA-Seq profile data.

BACKGROUND: The world has been battling the continuous COVID-19 pandemic spread by the SARS-CoV-2 virus for last two years. The issue of viral disease prediction is constantly a matter of interest in virology and the study of disease transmission over the long years. OBJECTIVE: In this study, we aimed to implement genome association studies using RNA-Seq of COVID-19 and reveal highly expressed gene biomarkers and prediction based on the machine learning model of COVID-19 analysis to combat this pandemic. METHOD: We collected RNA-Seq gene count data for both healthy (Control) and non-healthy (Treated) COVID-19 cases. In this experiment, a sequence of bioinformatics strategies and statistical techniques, such as fold-change and adjusted p-value, were processed to identify differentially expressed genes (DEGs). We filtered biomarker sets of high DEGs, moderate DEGs, and low DEGs using DESeq2, Limma Trend, and Limma Voom methods based on intersection and union operations and applied machine learning techniques to predict COVID-19. RESULT: Through experimental analysis, 67 potential biomarkers were extracted, comprising 49 up-regulated and 18 down-regulated genes, using statistical techniques and a set-theory consensus strategy. We trained the machine learning models on 12 different biomarker sets and found that the SVM model performed better than the other classifiers with 99.07% classification accuracy for moderate DEGs. CONCLUSION: Our study revealed that identified differentially expressed genes of the moderate DEGs biomarker set, |log2FC| ≥ 2 with adjusted p-value < 0.05, work significantly as input features to implement a machine learning model using a kernel-based SVM technique to predict COVID-19.

Are Substance Dependent Struggling for Utilizing the Services during COVID-19

COVID-19 infection and lockdown strategies both are impacted to the human life negatively. Treatment modes, techniques and accessibility to the Healthcare system became compromising during the pandemic. This article aims to understand different problematic aspect in service utilization of addiction services. Due to lockdown people with substance abuse leads to relapse and resulting use of multiple substance, that can be cause severe health complications like withdrawal and worsen to death. So, these conditions are making them prone to procure drugs in illegal way. This crisis has paved the path towards development and acceptance of digital psychiatry as a mode of treatment.