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Aims: To investigate the prevalence of workplace violence and its associated factors among Bangladeshi registered nurses., Background: Workplace violence is prevalent among nurses, particularly in developing countries. However, the issue has never been examined in Bangladeshi nurses., Methods: Between February 26 and July 10, 2021, this cross-sectional survey involving 1264 registered nurses was conducted. Workplace violence was determined by the Workplace Violence Scale (WVS). A multivariable logistic regression model was fitted to find the factors associated with workplace violence. This study complies with the EQUATOR (STROBE) checklist., Results: Of the 1264 nurses, 885 (70%) nurses reported being exposed to workplace violence in the previous year. Three hundred twenty-four (324; 25.6%) nurses reported physical violence, whereas 902 (71.4%) nurses reported nonphysical violence. According to the multivariable logistic regression model, male nurses, nurses in the Sylhet division, emergency department nurses, nurses working extended hours, and non trained nurses to tackle workplace violence were prone to physical violence. Furthermore, public hospital nurses and non trained nurses to tackle workplace violence were more likely to be exposed to nonphysical violence. Nurses who had not been exposed to workplace violence were satisfied with their current job, but those who had been exposed to workplace violence were dissatisfied and intended to leave their current job., Conclusions and Implications for Nursing and Health Policy: High prevalence of workplace violence underscores nurses' current working conditions, which are particularly poor in public hospitals and emergency departments. Moreover, the COVID-19 pandemic put unprecedented pressure on the whole healthcare system and caused various difficulties for healthcare workers. To develop a zero-violence practice environment, health authorities should implement policy-level interventions. Healthcare staff should be guided to deal more successfully with patients and coworkers to create a positive working environment., (© 2022 International Council of Nurses.)

COVID-19 has taken a huge toll on our lives over the last 3 years. Global initiatives put forward by all stakeholders are still in place to combat this pandemic and help us learn lessons for future ones. While the vaccine rollout was not able to curb the spread of the disease for all strains, the research community is still trying to develop effective therapeutics for COVID-19. Although Paxlovid and remdesivir have been approved by the FDA against COVID-19, they are not free of side effects. Therefore, the search for a therapeutic solution with high efficacy continues in the research community. To support this effort, in this latest version (v3) of COVID-19Base, we have summarized the biomedical entities linked to COVID-19 that have been highlighted in the scientific literature after the vaccine rollout. Eight different topic-specific dictionaries, i.e., gene, miRNA, lncRNA, PDB entries, disease, alternative medicines registered under clinical trials, drugs, and the side effects of drugs, were used to build this knowledgebase. We have introduced a BLSTM-based deep-learning model to predict the drug-disease associations that outperforms the existing model for the same purpose proposed in the earlier version of COVID-19Base. For the very first time, we have incorporated disease-gene, disease-miRNA, disease-lncRNA, and drug-PDB associations covering the largest number of biomedical entities related to COVID-19. We have provided examples of and insights into different biomedical entities covered in COVID-19Base to support the research community by incorporating all of these entities under a single platform to provide evidence-based support from the literature. COVID-19Base v3 can be accessed from: https://covidbase-v3.vercel.app/. The GitHub repository for the source code and data dictionaries is available to the community from: https://github.com/91Abdullah/covidbasev3.0., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Basit, Qureshi, Musleh, Guler, Rahman, Biswas and Alam.)

Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small-protein β 2 -microglobulin (β 2 m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. In virus-infected cells, these peptides may include those derived from viral proteins. Peptide-MHC-I complexes then traffic through the secretory pathway and are displayed at the cell surface where those containing viral peptides can be detected by CD8 + T lymphocytes that kill infected cells. Many viruses enhance their in vivo survival by encoding genes that down-regulate MHC-I expression to avoid CD8 + T cell recognition. Here, we report that two accessory proteins encoded by SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, down-regulate MHC-I expression using distinct mechanisms. First, ORF3a, a viroporin, reduces the global trafficking of proteins, including MHC-I, through the secretory pathway. The second, ORF7a, interacts specifically with the MHC-I heavy chain, acting as a molecular mimic of β 2 m to inhibit its association. This slows the exit of properly assembled MHC-I molecules from the endoplasmic reticulum. We demonstrate that ORF7a reduces antigen presentation by the human MHC-I allele HLA-A*02:01. Thus, both ORF3a and ORF7a act post-translationally in the secretory pathway to lower surface MHC-I expression, with ORF7a exhibiting a specific mechanism that allows immune evasion by SARS-CoV-2.

The recent global health emergency caused by the coronavirus disease 2019 (COVID-19) pandemic has taken a heavy toll, both in terms of lives and economies. Vaccines against the disease have been developed, but the efficiency of vaccination campaigns worldwide has been variable due to challenges regarding production, logistics, distribution and vaccine hesitancy. Furthermore, vaccines are less effective against new variants of the SARS-CoV-2 virus and vaccination-induced immunity fades over time. These challenges and the vaccines' ineffectiveness for the infected population necessitate improved treatment options, including the inhibition of the SARS-CoV-2 main protease (M pro ). Drug repurposing to achieve inhibition could provide an immediate solution for disease management. Here, we used structure-based virtual screening (SBVS) to identify natural products (from NP-lib) and FDA-approved drugs (from e-Drug3D-lib and Drugs-lib) which bind to the M pro active site with high-affinity and therefore could be designated as potential inhibitors. We prioritized nine candidate inhibitors (e-Drug3D-lib: Ciclesonide, Losartan and Telmisartan; Drugs-lib: Flezelastine, Hesperidin and Niceverine; NP-lib: three natural products) and predicted their half maximum inhibitory concentration using DeepPurpose, a deep learning tool for drug-target interactions. Finally, we experimentally validated Losartan and two of the natural products as in vitro M pro inhibitors, using a bioluminescence resonance energy transfer (BRET)-based M pro sensor. Our study suggests that existing drugs and natural products could be explored for the treatment of COVID-19.

Objectives: To investigate burnout among Bangladeshi nurses and the factors that influence it, particularly the association of workplace bullying (WPB) and workplace violence (WPV) with burnout. Methods: This cross-sectional study collected data from 1,264 Bangladeshi nurses. Mixed-effects Poisson regression models were fitted to find the adjusted association between WPB, WPV, and burnout. Results: Burnout was found to be prevalent in 54.19% of 1,264 nurses. 61.79% of nurses reported that they had been bullied, and 16.3% of nurses reported experience of "intermediate and high" levels of workplace violence in the previous year. Nurses who were exposed to "high risk bullying" (RR = 2.29, CI: 1.53-3.41) and "targeted bullying" (RR = 4.86, CI: 3.32-7.11) had a higher risk of burnout than those who were not. Similarly, WPV exposed groups at "intermediate and high" levels had a higher risk of burnout (RR = 3.65, CI: 2.40-5.56) than WPV non-exposed groups. Conclusion: Nurses' burnout could be decreased if issues like violence and bullying were addressed in the workplace. Hospital administrators, policymakers, and the government must all promote and implement an acceptable working environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chowdhury, Kabir, Chowdhury and Hossain.)

Background: Depression is one of the most serious yet understudied issues among Bangladeshi nurses, bringing health dangers to this workforce. This study aimed to investigate how workplace violence (WPV), bullying, burnout, and job satisfaction are correlated with depression and identify the factors associated with depression among Bangladeshi nurses., Methods: For this cross-sectional study, data were collected between February 26, 2021, and July 10, 2021 from the Bangladeshi registered nurses. The Workplace Violence Scale (WPVS), the Short Negative Acts Questionnaire [S-NAQ], the Burnout Measure-Short version (BMS), the Short Index of Job Satisfaction (SIJS-5), and the Patient Health Questionnaire (PHQ-9) were used to measure WPV, bullying, burnout, job satisfaction, and depression, respectively. Inferential statistics include Pearson's correlation test, t-test, one-way ANOVA test, multiple linear regression, and multiple hierarchal regression analyses were performed., Results: The study investigated 1,264 nurses (70.02% female) with an average age of 28.41 years (SD = 5.54). Depression was positively correlated with WPV, bullying, and burnout and negatively correlated with job satisfaction (p <0.001). According to the multiple linear regression model, depression was significantly lower among nurses with diploma degrees (β = -1.323, 95% CI = -2.149 to -0.497) and bachelor's degrees (β = -1.327, 95% CI = -2.131 to- 0.523) compared to the nurses with master's degree. The nurses who worked extended hours (>48 hours) had a significantly higher depression score (β = 1.490, 95% CI = 0.511 to 2.470) than those who worked ≤ 36 hours. Depression was found to be significantly higher among those who did not receive a timely salary (β = 2.136, 95% CI = 1.138 to 3.134), rewards for good works (β = 1.862, 95% CI = 1.117 to 2.607), and who had no training on WPV (β = 0.895, 95% CI = 0.092 to 1.698)., Conclusions: Controlling burnout, bullying, and workplace violence, as well as improving the work environment for nurses and increasing job satisfaction, are the essential indicators of reducing depression. This can be accomplished with integrative support from hospital executives, policymakers, and government officials., Competing Interests: The authors have declared that no competing interests exist.

Background: The COVID-19 pandemic has compelled all educational institutions from the conventional campus-based education system to e-learning worldwide. However, adapting to this new platform, e-learning readiness may cause perceived stress among students. This study aimed to examine the association between e-learning readiness and perceived e-learning stress and the relationship between sociodemographic and e-learning related factors., Results: A cross-sectional study was employed, where 1145 e-learning enrolled university students were surveyed. The result indicated that nearly 91% of students reported moderate (76.07%) to the higher level (14.85%) of perceived e-learning stress, whereas more than half of them (58.17%) were at the sub-optimum level of readiness. Furthermore, it was found that students with the sub-optimum level of readiness compared to optimum had a significantly higher chance of reporting moderate and high level of perceived e-learning stress. Besides, parents' highest education, residence, students' preference in (e-learning or learning format), and having any eye problems were associated with perceived e-learning stress., Conclusions: A sudden introduction of e-learning during the COVID-19 catastrophe has brought about challenges, including the students' readiness, that might exacerbate the perceived stress level in different ways. This study reported that most of the students were at sub-optimal levels of readiness and suffered from moderate to high levels of perceived e-learning stress. The findings should integrate into the education monitoring system to enhance students' coping strategies, incite readiness, straighten, and nourish existing policies.Key messagesThe moderate and higher level of e-learning stress was 76% and 15%, respectively.Here, 58% of students were at the sub-optimum level of e-learning readiness.Students' sub-optimum level of e-learning readiness was significantly associated with the perceived moderate and high level of e-learning stress.

Background: E-learning is a relatively trending system of education that has been placed over conventional campus-based learning worldwide, especially since the emergence of the COVID-19 pandemic. This study aimed to assess e-learning readiness among university students of a developing country like Bangladesh and identify the independent predictors of e-learning readiness., Methods: From 26 December 2020 to 11 January 2021, a total of 1162 university students who had enrolled for e-learning completed a semi-structured questionnaire. Data were collected online via "Google Form" following the principles of snowball sampling through available social media platforms in Bangladesh. A multivariable linear regression model was fitted to investigate the association of e-learning readiness with perceived e-learning stress and other independent predictor variables., Results: A total of 1162 university students participated in this study. The results indicated that with the increase of students' perceived e-learning stress score, the average e-learning readiness score was significantly decreased (β = -0.43, 95% CI: -0.66, -0.20). The students did not seem ready, and none of the e-learning readiness scale items reached the highest mean score (5.0). The age, gender, divisional residence, preference of students and their parents, devices used, and having any eye problems were significantly associated with the students' e-learning readiness., Conclusion: During the prolonged period of the COVID-19 pandemic, e-learning implication strategies are needed to be assessed systematically with the level of readiness and its' impacts among students for the continuation of sound e-learning systems. The study findings recommend evaluating the e-learning readiness of university students and the mental health outcomes during the COVID-19 catastrophe in Bangladesh., Competing Interests: The authors have declared that no competing interests exist.

Acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called COVID-19, is one of the most contagious viruses resulting in a progressive pandemic. Since specific antiviral treatments have not been developed yet and its fatal rate is almost high, early and fast detection is critical for controlling the outbreak. In this study, a piezoelectric microcantilever biosensor has been designed for detecting COVID-19 samples directly without requiring preparation steps. The biosensor acts as a transducer and is coated with the related antibody. When the SARS-CoV-2 antigens adsorbed on the microcantilever top surface through their spike proteins, a surface stress due to the mass change would be prompted leading to the measurable tip deflection and floating voltage. To obtain a biosensor with optimum parameters, different shapes and piezoelectric materials have been assessed and it was concluded that a Poly (vinylidene fluoride) (PVDF) biosensor in a shape of a holed punched form triangle, represented the best result. Therefore, the highly sensitive microcantilever biosensor can detect COVID-19 in clinical samples with various viral loads, rapidly. Also, it is selective enough to differentiate SARS-CoV-2 from other viruses with similar symptoms.

This paper describes the potential impact of the coronavirus disease 2019 (COVID-19) pandemic on the readymade garment (RMG) workers of Bangladesh. It articulates the RMG workers' existing vulnerability during the COVID-19 pandemic based on currently available evidence and personal conversations/communications with RMG workers. COVID-19 has already impacted RMG workers' health (both physical and mental health status) and wellbeing, and resulted in loss of employment. We argue that the COVID-19 pandemic will have long-lasting effects on the garment workers, especially related to their health issues, financial hardship and inability to pay for essentials such as food, and future employment opportunities. The stakeholders (such as the international retailers/brands, Bangladesh Garment Manufacturers and Exporters Association, Government of Bangladesh) responsible for the global supply chain RMG factories should reconsider the health and overall wellbeing needs of the RMG workers during the ongoing COVID-19 pandemic., (© The Author(s) 2020. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Anti-COVID19 drugs, such as nirmatrelvir, have been developed targeting the SARS-CoV-2 main protease, Mpro, based on the critical requirement of its proteolytic processing of the viral polyproteins into functional proteins essential for viral replication. However, the emergence of SARS-CoV-2 variants with Mpro mutations has raised the possibility of developing resistance against these drugs, likely due to therapeutic targeting of the Mpro catalytic site. An alternative to these drugs is the development of drugs that target an allosteric site distant from the catalytic site in the protein that may reduce the chance of the emergence of resistant mutants. Here, we combine computational analysis with in vitro assay and report the discovery of a potential allosteric site and an allosteric inhibitor of SARS-CoV-2 Mpro. Specifically, we identified an Mpro metastable state with a deformed catalytic site harboring potential allosteric sites, raising the possibility that stabilization of this metastable state through ligand binding can lead to the inhibition of Mpro activity. We then performed a computational screening of a library (∼4.2 million) of drug-like compounds from the ZINC database and identified several candidate molecules with high predicted binding affinity. MD simulations showed stable binding of the three top-ranking compounds to the putative allosteric sites in the protein. Finally, we tested the three compounds in vitro using a BRET-based Mpro biosensor and found that one of the compounds (ZINC4497834) inhibited the Mpro activity. We envisage that the identification of a potential allosteric inhibitor of Mpro will aid in developing improved anti-COVID-19 therapy.

The need for the early detection of emerging pathogenic viruses and their newer variants has driven the urgent demand for developing point-of-care diagnostic tools. Although nucleic acid-based methods such as reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and loop-mediated isothermal amplification (LAMP) have been developed, a more facile and robust platform is still required. To address this need, as a proof-of-principle study, we engineered a prototype—the versatile, sensitive, rapid, and cost-effective bioluminescence resonance energy transfer (BRET)-based biosensor for oligonucleotide detection (BioOD). Specifically, we designed BioODs against the SARS-CoV-2 parental (Wuhan strain) and B.1.617.2 Delta variant through the conjugation of specific, fluorescently modified molecular beacons (sensor module) through a complementary oligonucleotide handle DNA functionalized with the NanoLuc (NLuc) luciferase protein such that the dissolution of the molecular beacon loop upon the binding of the viral oligonucleotide will result in a decrease in BRET efficiency and, thus, a change in the bioluminescence spectra. Following the assembly of the BioODs, we determined their kinetics response, affinity for variant-specific oligonucleotides, and specificity, and found them to be rapid and highly specific. Furthermore, the decrease in BRET efficiency of the BioODs in the presence of viral oligonucleotides can be detected as a change in color in cell phone camera images. We envisage that the BioODs developed here will find application in detecting viral infections with variant specificity in a point-of-care-testing format, thus aiding in large-scale viral infection surveillance.

The SARS-CoV-2 Omicron variant containing 15 mutations, including the unique Q493R, in the spike protein receptor binding domain (S1-RBD) is highly infectious. While comparison with previously reported mutations provide some insights, the mechanism underlying the increased infections and the impact of the reversal of the unique Q493R mutation seen in BA.4, BA.5, BA.2.75, BQ.1 and XBB lineages is not yet completely understood. Here, using structural modelling and molecular dynamics (MD) simulations, we show that the Omicron mutations increases the affinity of S1-RBD for ACE2, and a reversal of the unique Q493R mutation further increases the ACE2-S1-RBD affinity. Specifically, we performed all atom, explicit solvent MD simulations using a modelled structure of the Omicron S1-RBD-ACE2 and compared the trajectories with the WT complex revealing a substantial reduction in the Cα-atom fluctuation in the Omicron S1-RBD and increased hydrogen bond and other interactions. Residue level analysis revealed an alteration in the interaction between several residues including a switch in the interaction of ACE2 D38 from S1-RBD Y449 in the WT complex to the mutated R residue (Q493R) in Omicron complex. Importantly, simulations with Revertant (Omicron without the Q493R mutation) complex revealed further enhancement of the interaction between S1-RBD and ACE2. Thus, results presented here not only provide insights into the increased infectious potential of the Omicron variant but also a mechanistic basis for the reversal of the Q493R mutation seen in some Omicron lineages and will aid in understanding the impact of mutations in SARS-CoV-2 evolution.

Background: SARS-CoV-2 variants continue to spread throughout the world and cause waves of COVID-19 infections. It is important to find effective antiviral drugs to combat SARS-CoV-2 and its variants. The main protease (Mpro) of SARS-CoV-2 is a promising therapeutic target due to its crucial role in viral replication and its conservation in all the variants. Therefore, the aim of this work was to identify an effective inhibitor of Mpro. Methods: We studied around 200 antimicrobial peptides using in silico methods including molecular docking and allergenicity and toxicity prediction. One selected antiviral peptide was studied experimentally using a Bioluminescence Resonance Energy Transfer (BRET)-based Mpro biosensor, which reports Mpro activity through a decrease in energy transfer. Results: Molecular docking identified one natural antimicrobial peptide, Protegrin-2, with high binding affinity and stable interactions with Mpro allosteric residues. Furthermore, free energy calculations and molecular dynamics simulation illustrated a high affinity interaction between the two. We also determined the impact of the binding of Protegrin-2 to Mpro using a BRET-based assay, showing that it inhibits the proteolytic cleavage activity of Mpro. Conclusions: Our in silico and experimental studies identified Protegrin-2 as a potent inhibitor of Mpro that could be pursued further towards drug development against COVID-19 infection.

Coronavirus Disease of 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a massive health crisis across the globe, with some genetic variants gaining enhanced infectivity and competitive fitness, and thus significantly aggravating the global health concern. In this regard, the recent SARS-CoV-2 alpha, beta, and gamma variants (B.1.1.7, B.1.351, and P.1 lineages, respectively) are of great significance in that they contain several mutations that increase their transmission rates as evident from clinical reports. By the end of March 2021, these variants were accounting for about two-thirds of SARS-CoV-2 variants circulating worldwide. Specifically, the N501Y mutation in the S1 spike receptor binding domain (S1-RBD) of these variants have been reported to increase its affinity for ACE2, although the basis for this is not entirely clear yet. Here, we dissect the mechanism underlying the increased binding affinity of the N501Y mutant for ACE2 using molecular dynamics (MD) simulations of the available ACE2-S1-RBD complex structure (6M0J) and show a prolonged and stable interfacial interaction of the N501Y mutant S1-RBD with ACE2 compared to the wild type S1-RBD. Additionally, we find that the N501Y mutant S1-RBD displays altered dynamics that likely aids in its enhanced interaction with ACE2. By elucidating a mechanistic basis for the increased affinity of the N501Y mutant S1-RBD for ACE2, we believe that the results presented here will aid in developing therapeutic strategies against SARS-CoV-2 including designing of therapeutic agents targeting the ACE2-S1-RBD interaction.

Tremendous changes have been witnessed in the post-COVID-19 world. Global efforts were initiated to reach a successful treatment for this emerging disease. These efforts have focused on developing vaccinations and/or finding therapeutic agents that can be used to combat the virus or reduce its accompanying symptoms. Gulf Cooperation Council (GCC) countries have initiated efforts on many clinical trials to address the efficacy and the safety of several therapeutic agents used for COVID-19 treatment. In this article, we provide an overview of the GCC's clinical trials and associated drugs' discovery process in the pursuit of an effective medication for COVID-19. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims Antimicrobial resistance (AMR), a global health crisis of mounting urgency, has been further complicated by the ongoing COVID‐19 pandemic. The intricate relationship between these two phenomena is especially pronounced in low‐ and middle‐income countries (LMICs) due to the distinct obstacles encountered by their healthcare systems and policy structures. This study aims to explore the complex challenges arising from the coexistence of these two crises in LMICs and proffer specific recommendations for holistic management. Methods An exhaustive bibliographic survey was executed, employing search queries in specialized databases such as PubMed, SCOPUS, and Web of Science's SCI‐EXPANDED index. The timeframe for the literature search extended from January 2020 to January 2023. The search strategy employed key terms including antibiotic resistance, AMR, COVID‐19 pandemic, low‐ and middle‐income countries, SARS‐CoV‐2, and LMICs. Results The pandemic has aggravated various drivers of AMR in LMICs, including limited capabilities, weak frameworks, and socioeconomic factors. New challenges have emerged, such as disruptions in the antibiotic supply chain and an increased risk of healthcare‐associated infections. The interaction between these drivers presents a complex problem that demands a coordinated response. Specific recommendations include strengthening health systems, funding research and innovation, and enhancing infection prevention control measures. Conclusion The coexistence of AMR and the COVID‐19 pandemic in LMICs demands an integrated approach involving multiple stakeholders. Emphasis must be placed on constructing aligned regulatory frameworks, nurturing regional collaborations, and focusing on accessible therapeutic options. The study underscores the necessity for actionable strategies to achieve sustainable access to clean water and sanitation and also highlights the importance of long‐term planning, funding, and specialized expertise in emerging modalities like phage therapy.