UBA1-CDK16: A Sex-Specific Chimeric RNA and Its Role in Immune Sexual Dimorphism (preprint)

RNA processing mechanisms, such as alternative splicing and RNA editing, have been recognized as critical means to expand the transcriptome. Chimeric RNAs formed by intergenic splicing provide another potential layer of RNA diversification. By analyzing a large set of RNA-Seq data and validating results in over 1,200 blood samples, we identified UBA1-CDK16, a female-specific chimeric transcript. Intriguingly, both parental genes, are expressed in males and females. Mechanistically, UBA1-CDK16 is produced by cis-splicing between the two adjacent X-linked genes, originating from the inactive X chromosome. A female-specific chromatin loop, formed between the junction sites, facilitates the alternative splicing of its readthrough precursor. This unique chimeric transcript exhibits evolutionary conservation, evolving to be female-specific from non-human primates to humans. Furthermore, our investigation reveals that UBA1-CDK16 is enriched in the myeloid lineage and plays a regulatory role in myeloid differentiation. Notably, female COVID-19 patients who tested negative for this chimeric transcript displayed higher counts of neutrophils, highlighting its potential role in disease pathogenesis. These findings support the notion that chimeric RNAs represent a new repertoire of transcripts that can be regulated independently from the parental genes, and a new class of RNA variance with potential implications in sexual dimorphism and immune responses.

Mpox vaccination in global perspective: priorities and challenges.

After the global panic created by COVID-19, the monkeypox (Mpox) virus emerged as a new challenge for the world population. As of 19 January 2023, a total of 84,733 cases across 110 countries/territories including 80 deaths has been reported. The virus has been transmitted to nonendemic countries in a short span of 6 months warranting WHO to declare Mpox, a Public Health Emergency of International Concern on 23 July 2022. As the Mpox virus is crossing geographical boundaries without established transmission patterns, there is an urgent need for new scientific strategies from global researchers to contain it before turning into the next pandemic. The control of Mpox outbreaks primarily relies on various public health measures such as proper surveillance, contact tracing, rapid diagnosis, isolation and care of patients, and vaccination. At present, there are three vaccines viz. ACAM2000, MVABN, and LC16 are in consideration and have been approved in several jurisdictions for ongoing Mpox outbreak. Prioritization of individuals along with the production of specific Mpox vaccine is need of the hour to meet out the global demand of Mpox vaccination.

COVID-19 vaccine acceptance in South Asia: a multi-country study.

OBJECTIVES: With COVID-19 vaccination underway, this study aimed to understand belief, attitude and intention of the people in the South Asia region towards the vaccine. METHODS: We conducted a cross-sectional study using semi-structured questionnaires among 18201 individuals in four South Asian countries; Bangladesh, India, Pakistan, and Nepal between January 17 and February 2, 2021. We used the Health Belief Model (HBM) to identify the predictors related to vaccine acceptance. STATA (v16.1) was used for all analyses. RESULTS: The percentage of respondents willing to be vaccinated against COVID-19 was 65%, 66%, 72% and 74% for Bangladesh, India, Pakistan and Nepal, respectively. Perceived destructive impact of COVID-19, positive perception of vaccines and concern about possible side effects were significant in modifying respondents' intentions.. In multivariable logistic regression, age, sex, marital status, education, comorbidities, worry about getting infected, perceived COVID-19 impact, belief regarding vaccine efficacy, positive attitude towards mandatory measures, and vaccine availability were found to be associated with vaccine acceptance across countries. CONCLUSION: Nearabout two-third of the respondants were willing to take COVID-19 vaccine in the four South Asia countries.

A systematic review of the smartphone applications available for coronavirus disease 2019 (COVID19) and their assessment using the mobile app rating scale (MARS)

The global impact of COVID-19 pandemic has increased the need to rapidly develop and improve utilization of mobile applications across the healthcare continuum to address rising barriers of access to care due to social distancing challenges and allow continuity in sharing of health information, assist with COVID-19 activities including contact tracing, and providing useful information as needed. Here we provide an overview of mobile applications being currently utilized for COVID-19 related activities. We performed a systematic review of the literature and mobile platforms to assess mobile applications been currently utilized for COVID-19, and quality assessment of these applications using the Mobile Application Rating Scale (MARS) for overall quality, Engagement, Functionality, Aesthetics, and Information. Finally, we provide an overview of the key salient features that should be included in mobile applications being developed for future use. Our search identified 63 apps that are currently being used for COVID-19. Of these, 25 were selected from the Google play store and Apple App store in India, and 19 each from the UK and US. 18 apps were developed for sharing up to date information on COVID-19, and 8 were used for contact tracing while 9 apps showed features of both. On MARS Scale, overall scores ranged from 2.4 to 4.8 with apps scoring high in areas of functionality and lower in Engagement. Future steps should involve developing and testing of mobile applications using assessment tools like the MARS scale and the study of their impact on health behaviors and outcomes.

Exploration of antigenic determinants in spike glycoprotein of SARS-CoV2 and identification of five salient potential epitopes.

Emerging pathogens have been an eternal threat to mankind. In a series of pandemics caused by notorious coronaviruses, a newly emerged SARS-CoV2 virus is creating panic among the world population. The unavailability of reliable theranostics insists the exploration of antigenic determinants in spike glycoprotein of SARS-CoV2. The four novel inserts ('70VSGTNGT76', '150KSWM153', 247SYLTPG252 and 674QTQTNSPRR682) in SARS-CoV2 spike protein were unraveled via multiple sequence alignment of spike proteins of SARS-CoV2, SARS-CoV, and MERS-CoV. The three-dimension (3D) modeling of the spike protein of the SARS-CoV2 and their interaction with the ACE2 receptor was delineated with the help of SWISS-MODEL and 3DLigandSite web servers. The predicted 3D model of SARS-CoV2 was further verified by SAVES, RAMPAGE, and ProSA-web tools. The potential B-cell immunogenic epitopes of SARS-CoV2 were predicted out by using various software viz. IEDB B-cell epitopes prediction tool, BepiPred linear epitope prediction tool, Emini Surface Accessibility Prediction tool, and Kolaskar-Tongaonkar antigenicity web tool. The five epitopes (i.e. '71SGTNGTKRFDN81, 247SYLTPG252, 634RVYST638, 675QTQTNSPRRARSV687, and 1054QSAPH1058) were selected as potent antigenic determinants. The quantum of information generated by this study will prove beneficial for the development of effective therapeutics, diagnostics, and multi-epitopic vaccines to combat this ongoing menace.

The role of disinfectants and sanitizers during COVID-19 pandemic: advantages and deleterious effects on humans and the environment.

Disinfectants and sanitizers are essential preventive agents against the coronavirus disease 2019 (COVID-19) pandemic; however, the pandemic crisis was marred by undue hype, which led to the indiscriminate use of disinfectants and sanitizers. Despite demonstrating a beneficial role in the control and prevention of COVID-19, there are crucial concerns regarding the large-scale use of disinfectants and sanitizers, including the side effects on human and animal health along with harmful impacts exerted on the environment and ecological balance. This article discusses the roles of disinfectants and sanitizers in the control and prevention of the current pandemic and highlights updated disinfection techniques against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This article provides evidence of the deleterious effects of disinfectants and sanitizers exerted on humans, animals, and the environment as well as suggests mitigation strategies to reduce these effects. Additionally, potential technologies and approaches for the reduction of these effects and the development of safe, affordable, and effective disinfectants are discussed, particularly, eco-friendly technologies using nanotechnology and nanomedicine.

SARS-CoV-2 infection during pregnancy and pregnancy-related conditions: Concerns, challenges, management and mitigation strategies-a narrative review.

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health problem. The SARS-CoV-2 triggers hyper-activation of inflammatory and immune responses resulting in cytokine storm and increased inflammatory responses on several organs like lungs, kidneys, intestine, and placenta. Although SARS-CoV-2 affects individuals of all age groups and physiological statuses, immune-compromised individuals such as pregnant women are considered as a highly vulnerable group. This review aims to raise the concerns of high risk of infection, morbidity and mortality of COVID-19 in pregnant women and provides critical reviews of pathophysiology and pathobiology of how SARS-CoV-2 infection potentially increases the severity and fatality during pregnancy. This article also provides a discussion of current evidence on vertical transmission of SARS-CoV-2 during pregnancy and breastfeeding. Lastly, guidelines on management, treatment, preventive, and mitigation strategies of SARS-CoV-2 infection during pregnancy and pregnancy-related conditions such as delivery and breastfeeding are discussed.

Physiological implications of COVID-19 in reproduction: angiotensin-converting enzyme 2 a key player.

The COVID-19 outbreak, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was first identified in China, and it has quickly become a global threat to public health due to its rapid rate of transmission and fatalities. Angiotensin-converting enzyme 2 (ACE2) has been identified as a receptor that mediates the entry of SARS-CoV-2 into human cells, as in the case of severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have reported that ACE2 expression is higher in Leydig, Sertoli and seminiferous ductal cells of males, as well as in ovarian follicle cells of females, suggesting possible potential pathogenicity of the coronavirus in the reproductive system. Higher ACE2 expression in the human placenta and reports of vertical transmission of SARS-CoV-2 among clinical cases have increased the relevance of further studies in this area. This review focuses on the interaction between SARS-CoV-2 and the ACE2 receptor and speculates on the mechanistic interplay in association with male and female reproductive physiology. In addition, based on the available literature, we discuss the alleged sex differences in terms of the infectivity of SARS-CoV-2, which is claimed greater among males, and further explore the physiological role of ACE2 and 17ß-oestradiol for the same.

MERS-CoV: epidemiology, molecular dynamics, therapeutics, and future challenges.

The Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has gained research attention worldwide, given the current pandemic. Nevertheless, a previous zoonotic and highly pathogenic coronavirus, the Middle East Respiratory Syndrome coronavirus (MERS-CoV), is still causing concern, especially in Saudi Arabia and neighbour countries. The MERS-CoV has been reported from respiratory samples in more than 27 countries, and around 2500 cases have been reported with an approximate fatality rate of 35%. After its emergence in 2012 intermittent, sporadic cases, nosocomial infections and many community clusters of MERS continued to occur in many countries. Human-to-human transmission resulted in the large outbreaks in Saudi Arabia. The inherent genetic variability among various clads of the MERS-CoV might have probably paved the events of cross-species transmission along with changes in the inter-species and intra-species tropism. The current review is drafted using an extensive review of literature on various databases, selecting of publications irrespective of favouring or opposing, assessing the merit of study, the abstraction of data and analysing data. The genome of MERS-CoV contains around thirty thousand nucleotides having seven predicted open reading frames. Spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins are the four main structural proteins. The surface located spike protein (S) of betacoronaviruses has been established to be one of the significant factors in their zoonotic transmission through virus-receptor recognition mediation and subsequent initiation of viral infection. Three regions in Saudi Arabia (KSA), Eastern Province, Riyadh and Makkah were affected severely. The epidemic progression had been the highest in 2014 in Makkah and Riyadh and Eastern Province in 2013. With a lurking epidemic scare, there is a crucial need for effective therapeutic and immunological remedies constructed on sound molecular investigations.

SARS-CoV-2 existence in sewage and wastewater: A global public health concern?

The SARS-CoV-2/COVID-19 pandemic has spread across the globe and affected millions of individuals as of the efficient virus transmission potential mediated via multiple virus shedding routes. The presence of SARS-CoV-2 in the stool samples and its prolonged shedding in environmental compartments like sewage and wastewater signifies a potential threat adding to the transmission cycle of this novel virus. The potential role played by the asymptomatic COVID-19 patients in transmitting the disease via the fecal-oral route is now under investigation. Hence, in the present scenario, wastewater-based epidemiology, and sewage surveillance may provide valuable insights into the prevalence of SARS-CoV-2 among the human population and could serve as a sensitive surveillance system and a crucial early warning tool. Further studies are required to determine the survival of SARS-CoV-2 in the environment, transmissibility through wastewater, and the potential to infect humans via the fecal-oral route. Appropriate frameworks with regards to evaluation and analysis of SARS-CoV-2 will help implement appropriate intervention strategies and necessary sanitation practices to ensure virus free clean water supply to have a check on the further spread of this pandemic virus.

COVID-19 in the elderly people and advances in vaccination approaches.

The rapid worldwide spread of the COVID-19 pandemic, caused by the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in tens of millions of infections and over one million deaths. SARS-CoV-2 infection affects all age groups; however, those over 60 years old are affected more severely. Moreover, pre-existing co-morbidities result in higher COVID-19-associated mortality in the geriatric population. This article highlights the associated risk factors of SARS-CoV-2 infection in older people and progress in developing COVID-19 vaccines, especially for efficient vaccination of the older population. There is also a summary of immunomodulatory and immunotherapeutic approaches to ameliorate the outcome of COVID-19 in older individuals.

Plant-based vaccines and antibodies to combat COVID-19: current status and prospects.

Globally, researchers are undertaking significant efforts to design and develop effective vaccines, therapeutics, and antiviral drugs to curb the spread of coronavirus disease 2019 (COVID-19). Plants have been used for the production of vaccines, monoclonal antibodies, immunomodulatory proteins, drugs, and pharmaceuticals via molecular farming/transient expression system and are considered as bioreactors or factories for their bulk production. These biological products are stable, safe, effective, easily available, and affordable. Plant molecular farming could facilitate rapid production of biologics on an industrial scale, and has the potential to fulfill emergency demands, such as in the present situation of the COVID-19 pandemic. This article aims to describe the methodology and basics of plant biopharming, in addition to its prospective applications for developing effective vaccines and antibodies to counter COVID-19.

Knowledge, attitudes, and practices towards COVID-19 pandemic among residents of Jharkhand state, India: An online survey (preprint)

Background People's adherence to control measures is imperative in the fight against COVID-19. The present study was done to evaluate knowledge, attitudes, and practices towards COVID-19 among residents of Jharkhand and to assist government in deciding further course of action during the COVID-19 outbreak.Methods This study was an online cross sectional survey. The link to the questionnaire was displayed on the official website of Rajendra Institute of Medical Sciences, Ranchi, Government of Jharkhand, National Health Mission, Jharkhand, official website of all districts under Jharkhand state administration, Integrated Disease Surveillance Programme and Information & Public Relations department. Participation of residents in the survey was also extensively propagated using mass media mainly local television networks, radio channel and newspapers.Results A total of 4683 responses were received from all districts of Jharkhand. Majority of the participants were young adults (47.5%) and number of male participants was more than the females (81.4%). Mean correct knowledge score for participants of this study was 10.73 + 2.2 (maximum attainable score was 14) while mean practice score for the participants was 4.5 + 0.69 (maximum attainable score was 5). Knowledge score of the participants was significantly associated with their age, education status and economic class (p < 0.05). The participants largely held an optimistic attitude and healthy practices towards COVID-19.Conclusions Participants had positive attitude but were also logically worried and uncertain about near future. Adequate knowledge of participants was visible in the practices of residents. There was however a gap across age groups, gender, literacy and income levels which should be addressed in future campaigns.

Geriatric Population During the COVID-19 Pandemic: Problems, Considerations, Exigencies, and Beyond.

The coronavirus disease 2019 (COVID-19) pandemic wreaked havoc worldwide, with more than 20 million confirmed cases and nearly 0. 75 million deaths as of 10th August 2020. Various factors determine the severity and symptoms of this infection. Older age and underlying diseases are the challenges being faced in controlling and treating COVID-19. In 2019, 703 million of the global population was older than 65 years of age. The estimated mortality due to COVID-19 in people older than 76 years of age is reportedly 18%. Frequent infections in older people, higher disease severity, and increased mortality are major challenges in the implementation of appropriate preventive measures and future strategies to protect against this disease in geriatric population. Poor health status, weak immune function, lowered organ function, increased probability of multiple underlying diseases, and poor attention to personal health can increase the susceptibility to various diseases in the geriatric population. Concerning inadequate immunity, the decrease expression of receptors and exaggerated pathophysiologic responses can be debilitating. However, future studies will reveal the hidden facets in these aspects in this COVID-19 catastrophe. In this article, we reviewed the main concerns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the geriatric population, including the risk of acquiring severe COVID-19 resulting in mortality, variation in clinical manifestations, and other pandemic-related concerns. We also discussed the need for increasing attention toward the elderly, taking appropriate prevention and control measures, and considering geriatric-related adjustments in vaccine design and development.

BCG vaccine: a hope to control COVID-19 pandemic amid crisis.

COVID-19 caused by the virus SARS-CoV-2 has gripped essentially all countries in the world, and has infected millions and killed hundreds of thousands of people. Several innovative approaches are in development to restrain the spread of SARS-CoV-2. In particular, BCG, a vaccine against tuberculosis (TB), is being considered as an alternative therapeutic modality. BCG vaccine is known to induce both humoral and adaptive immunities, thereby activating both nonspecific and cross-reactive immune responses in the host, which combined could effectively resist other pathogens including SARS-CoV-2. Notably, some studies have revealed that SARS-CoV-2 infectivity, case positivity, and mortality rate have been higher in countries that have not adopted BCG vaccination than in countries that have done so. This review presents an overview of the concepts underlying BCG vaccination and its nonspecific immuological effects and protection, resulting in 'trained immunity' and potential utility for resisting COVID-19.

Coronavirus disease 2019 (COVID-19) in domestic animals and wildlife: advances and prospects in the development of animal models for vaccine and therapeutic research.

SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), is suspected to have been first contracted via animal-human interactions; it has further spread across the world by efficient human-to-human transmission. Recent reports of COVID-19 in companion animals (dogs and cats) and wild carnivores such as tigers have created a dilemma regarding its zoonotic transmission. Although in silico docking studies, sequence-based computational studies, and experimental studies have shown the possibility of SARS-CoV-2 infection and transmission in cats, ferrets, and other domestic/wild animals, the results are not conclusive of infection under natural conditions. Identifying the potential host range of SARS-CoV-2 will not only help prevent the possibility of human-to-animal and animal-to-human transmission but also assist in identifying efficient animal models that can mimic the clinical symptoms, transmission potential, and pathogenesis of the disease. Such an efficient animal model will accelerate the process of development and evaluation of vaccines, immunotherapeutics, and other remedies for SARS-CoV-2.

Possibility of SARS-CoV-2 transmission from the breast milk of COVID-19 affected women patients to their infants: worries and strategies to counter it.

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SARS-CoV-2/COVID-19 and advances in developing potential therapeutics and vaccines to counter this emerging pandemic.

A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China, which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 210 countries while affecting more than 25 million people and causing more than 843,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia, and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs, and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. To date, August 30, 2020, no effective, proven therapeutic antibodies or specific drugs, and vaccines have turned up. In this review article, we describe the underlying molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.

SARS-CoV-2 jumping the species barrier: Zoonotic lessons from SARS, MERS and recent advances to combat this pandemic virus.

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome - Coronavirus-2) of the family Coronaviridae, appeared in China in December 2019. This disease was declared as posing Public Health International Emergency by World Health Organization on January 30, 2020, attained the status of a very high-risk category on February 29, and now having a pandemic status (March 11). COVID-19 has presently spread to more than 215 countries/territories while killing nearly 0.75 million humans out of cumulative confirmed infected asymptomatic or symptomatic cases accounting to almost 20.5 million as of August 12, 2020, within a short period of just a few months. Researchers worldwide are pacing with high efforts to counter the spread of this virus and to design effective vaccines and therapeutics/drugs. Few of the studies have shown the potential of the animal-human interface and zoonotic links in the origin of SARS-CoV-2. Exploring the possible zoonosis and revealing the factors responsible for its initial transmission from animals to humans will pave ways to design and implement effective preventive and control strategies to counter the COVID-19. The present review presents a comprehensive overview of COVID-19 and SARS-CoV-2, with emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARS- and MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread, and highlights the new advances in diagnosis, vaccine and therapies, preventive and control measures, one health concept along with recent research developments to counter this pandemic disease.