Insights into the Transmission, Host Range, Genomics, Vaccination, and Current Epidemiology of the Monkeypox Virus.

This review delves into the historical context, current epidemiological landscape, genomics, and pathobiology of monkeypox virus (MPXV). Furthermore, it elucidates the present vaccination status and strategies to curb the spread of monkeypox. Monkeypox, caused by the Orthopoxvirus known as MPXV, is a zoonotic ailment. MPXV can be transmitted from person to person through respiratory droplets during prolonged face-to-face interactions. While many cases of monkeypox are self-limiting, vulnerable groups such as young children, pregnant women, and immunocompromised individuals may experience severe manifestations. Diagnosis predominantly relies on clinical presentations, complemented by laboratory techniques like RT-PCR. Although treatment is often not required, severe cases necessitate antiviral medications like tecovirimat, cidofovir, and brincidofovir. Vaccination, particularly using the smallpox vaccine, has proven instrumental in outbreak control, exhibiting an efficacy of at least 85% against mpox as evidenced by data from Africa. Mitigating transmission requires measures like wearing surgical masks, adequately covering skin lesions, and avoiding handling wild animals.

Comprehensive analysis of antigenic variations and genomic properties of hepatitis B virus in clinical samples in the mid-north east region of Bangladesh.

This investigation delineates an exhaustive analysis of the clinical, immunological, and genomic landscapes of hepatitis B virus (HBV) infection across a cohort of 22 verified patients. The demographic analysis unveiled a pronounced male bias (77.27%), with patient ages spanning 20 to 85 years and durations of illness ranging from 10 days to 4 years. Predominant clinical manifestations included fever, fatigue, anorexia, abdominal discomfort, and arthralgia, alongside observed co-morbidities such as chronic renal disorders and hepatocellular carcinoma. Antigenic profiling of the HBV envelope proteins elucidated significant heterogeneity among the infected subjects, particularly highlighted by discordances in the detection capabilities of small and large HBsAg assays, suggesting antigenic diversity. Quantitative assessment of viral loads unveiled a broad spectrum, accompanied by atypical HBeAg reactivity patterns, challenging the reliability of existing serological markers. Correlative studies between viral burden and antigenicity of the envelope proteins unearthed phenomena indicative of diagnostic evasion. Notably, samples demonstrating robust viral replication were paradoxically undetectable by the large HBsAg ELISA kit, advocating for more sophisticated diagnostic methodologies. Genotypic examination of three HBV isolates classified them as genotype D (D2), with phylogenetic alignment to strains from various global origins. Mutational profiling identified pivotal mutations within the basic core promoter and preS2/S1 regions, associated with an augmented risk of hepatocellular carcinoma. Further, mutations discerned in the small HBsAg and RT/overlap regions were recognized as contributors to vaccine and/or diagnostic escape mechanisms. In summation, this scholarly discourse elucidates the intricate interplay of clinical presentations, antigenic diversity, and genomic attributes in HBV infection, accentuating the imperative for ongoing investigative endeavors to refine diagnostic and therapeutic modalities.

COVID-19 and the brain: understanding the pathogenesis and consequences of neurological damage.

SARS-CoV-2 has been known remarkably since December 2019 as a strain of pathogenic coronavirus. Starting from the earlier stages of the COVID-19 pandemic until now, we have witnessed many cases of neurological damage caused by SARS-CoV-2. There are many studies and research conducted on COVID-19-positive-patients that have found brain-related abnormalities with clear neurological symptoms, ranging from simple headaches to life-threatening strokes. For treating neurological damage, knowing the actual pathway or mechanism of causing brain damage via SARS-CoV-2 is very important. For this reason, we have tried to explain the possible pathways of brain damage due to SARS-CoV-2 with mechanisms and illustrations. The SARS-CoV-2 virus enters the human body by binding to specific ACE2 receptors in the targeted cells, which are present in the glial cells and CNS neurons of the human brain. It is found that direct and indirect infections with SARS-CoV-2 in the brain result in endothelial cell death, which alters the BBB tight junctions. These probable alterations can be the reason for the excessive transmission and pathogenicity of SARS-CoV-2 in the human brain. In this precise review, we have tried to demonstrate the neurological symptoms in the case of COVID-19-positive-patients and the possible mechanisms of neurological damage, along with the treatment options for brain-related abnormalities. Knowing the transmission mechanism of SARS-CoV-2 in the human brain can assist us in generating novel treatments associated with neuroinflammation in other brain diseases.

COVID-19 in Bangladesh: Wave-centric assessments and mitigation measures for future pandemics.

The ongoing pandemic COVID-19 caused by Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) has wreaked havoc globally by affecting millions of lives. Although different countries found the implementation of emergency measures useful to combat the viral pandemic, many countries are still experiencing the resurgence of COVID-19 cases with new variants even after following strict containment guidelines. Country-specific lessons learned from the ongoing COVID-19 pandemic can be utilized in commencing a successful battle against the potential future outbreaks. In this article, we analyzed the overall scenario of the COVID-19 pandemic in Bangladesh from Alpha to Omicron variant and discussed the demographic, political, economic, social, and environmental influences on the mitigation strategies employed by the country to combat the pandemic. We also tried to explore the preparedness and precautionary measures taken by the responsible authorities, the choice of strategies implemented, and the effectiveness of the response initiated by the government and relevant agencies. Finally, we discussed the possible strategies that might help Bangladesh to combat future COVID-19 waves and other possible pandemics based on the experiences gathered from the ongoing COVID-19 pandemic.

Corrigendum: Insights into the coinfections of human immunodeficiency virus-hepatitis B virus, human immunodeficiency virus-hepatitis C virus, and hepatitis B virus-hepatitis C virus: prevalence, risk factors, pathogenesis, diagnosis, and treatment.

[This corrects the article DOI: 10.3389/fmicb.2021.780887.].

A computational approach to design a polyvalent vaccine against human respiratory syncytial virus.

Human Respiratory Syncytial Virus (RSV) is one of the leading causes of lower respiratory tract infections (LRTI), responsible for infecting people from all age groups-a majority of which comprises infants and children. Primarily, severe RSV infections are accountable for multitudes of deaths worldwide, predominantly of children, every year. Despite several efforts to develop a vaccine against RSV as a potential countermeasure, there has been no approved or licensed vaccine available yet, to control the RSV infection effectively. Therefore, through the utilization of immunoinformatics tools, a computational approach was taken in this study, to design a multi-epitope polyvalent vaccine against two major antigenic subtypes of RSV, RSV-A and RSV-B. Potential predictions of the T-cell and B-cell epitopes were followed by extensive tests of antigenicity, allergenicity, toxicity, conservancy, homology to human proteome, transmembrane topology, and cytokine-inducing ability. The peptide vaccine was modeled, refined, and validated. Molecular docking analysis with specific Toll-like receptors (TLRs) revealed excellent interactions with suitable global binding energies. Additionally, molecular dynamics (MD) simulation ensured the stability of the docking interactions between the vaccine and TLRs. Mechanistic approaches to imitate and predict the potential immune response generated by the administration of vaccines were determined through immune simulations. Subsequent mass production of the vaccine peptide was evaluated; however, there remains a necessity for further in vitro and in vivo experiments to validate its efficacy against RSV infections.

Computational designing of a novel subunit vaccine for human cytomegalovirus by employing the immunoinformatics framework.

Human cytomegalovirus (HCMV) is a widespread virus that can cause serious and irreversible neurological damage in newborns and even death in children who do not have the access to much-needed medications. While some vaccines and drugs are found to be effective against HCMV, their extended use has given rise to dose-limiting toxicities and the development of drug-resistant mutants among patients. Despite half a century's worth of research, the lack of a licensed HCMV vaccine heightens the need to develop newer antiviral therapies and vaccine candidates with improved effectiveness and reduced side effects. In this study, the immunoinformatics approach was utilized to design a potential polyvalent epitope-based vaccine effective against the four virulent strains of HCMV. The vaccine was constructed using seven CD8+ cytotoxic T lymphocytes epitopes, nine CD4+ helper T lymphocyte epitopes, and twelve linear B-cell lymphocyte epitopes that were predicted to be antigenic, non-allergenic, non-toxic, fully conserved, and non-human homologous. Subsequently, molecular docking study, protein-protein interaction analysis, molecular dynamics simulation (including the root mean square fluctuation (RMSF) and root mean square deviation (RMSD)), and immune simulation study rendered promising results assuring the vaccine to be stable, safe, and effective. Finally, in silico cloning was conducted to develop an efficient mass production strategy of the vaccine. However, further in vitro and in vivo research studies on the proposed vaccine are required to confirm its safety and efficacy.Communicated by Ramaswamy H. Sarma.

SARS-CoV-2 and dengue virus co-infection: Epidemiology, pathogenesis, diagnosis, treatment, and management.

SARS-CoV-2 and dengue virus co-infection cases have been on the rise in dengue-endemic regions as coronavirus disease 2019 (COVID-19) spreads over the world, posing a threat of a co-epidemic. The risk of comorbidity in co-infection cases is greater than that of a single viral infection, which is a cause of concern. Although the pathophysiologies of the two infections are different, the viruses have comparable effects within the body, resulting in identical clinical symptoms in the case of co-infection, which adds to the complexity. Overlapping symptoms and laboratory features make proper differentiation of the infections important. However, specific biomarkers provide precise results that can be utilised to diagnose and treat a co-infection, whether it is simply COVID-19, dengue, or a co-infection. Though their treatment is distinguished, it becomes more complicated in circumstances of co-infection. As a result, regardless of whatever infection the first symptom points to, confirmation diagnosis of both COVID-19 and dengue should be mandatory, particularly in dengue-endemic regions, to prevent health deterioration in individuals treated for a single infection. There is still a scarcity of concise literature on the epidemiology, pathophysiology, diagnosis, therapy, and management of SARS-CoV-2 and dengue virus co-infection. The epidemiology of SARS-CoV-2 and dengue virus co-infection, the mechanism of pathogenesis, and the potential impact on patients are summarised in this review. The possible diagnosis with biomarkers, treatment, and management of the SARS-CoV-2 and dengue viruses are also discussed. This review will shed light on the appropriate diagnosis, treatment, and management of the patients suffering from SARS-CoV-2 and dengue virus co-infection.

An In-Silico Identification of Potential Flavonoids against Kidney Fibrosis Targeting TGFßR-1.

Fibrosis is a hallmark of progressive kidney diseases. The overexpression of profibrotic cytokine, namely transforming growth factor ß (TGF-ß) due to excessive inflammation and tissue damage, induces kidney fibrosis. The inhibition of TGF-ß signaling is markedly limited in experimental disease models. Targeting TGF-ß signaling, therefore, offers a prospective strategy for the management of kidney fibrosis. Presently, the marketed drugs have numerous side effects, but plant-derived compounds are relatively safer and more cost-effective. In this study, TGFßR-1 was targeted to identify the lead compounds among flavonoids using various computational approaches, such as ADME/T (absorption, distribution, metabolism, and excretion/toxicity) analysis, molecular docking, and molecular dynamics simulation. ADME/T screening identified a total of 31 flavonoids with drug-like properties of 31 compounds, a total of 5 compounds showed a higher binding affinity to TGFßR-1, with Epicatechin, Fisetin, and Luteolin ranking at the top three (-13.58, -13.17, and -10.50 kcal/mol, respectively), which are comparable to the control drug linagliptin (-9.074 kcal/mol). The compounds also exhibited outstanding protein-ligand interactions. The molecular dynamic simulations revealed a stable interaction of these compounds with the binding site of TGFßR-1. These findings indicate that flavonoids, particularly Epicatechin, Fisetin, and Luteolin, may compete with the ligand-binding site of TGFßR-1, suggesting that these compounds can be further evaluated for the development of potential therapeutics against kidney fibrosis. Further, in-vitro and in-vivo studies are recommended to support the current findings.

3D Bioprinting for Regenerating COVID-19-Mediated Irreversibly Damaged Lung Tissue.

While the tension of COVID-19 is still increasing, patients who recovered from the infection are facing life-threatening consequences such as multiple organ failure due to the presence of angiotensin-converting enzyme 2 receptor in different organs. Among all the complications, death caused by respiratory failure is the most common because severe acute respiratory syndrome coronavirus 2 infects lung's type II epithelial, mucociliary, and goblet cells that eventually cause pneumonia and acute respiratory distress syndrome, which are responsible for the irreversible lung damage. Risk factors, such as age, comorbidities, diet, and lifestyle, are associated with disease severity. This paper reviews the potential of three-dimensional bioprinting in printing an efficient organ for replacement by evaluating the patient's condition.

Pathogenesis and potential therapeutic application of stem cells transplantation in Huntington's disease.

Huntington's disease (HD) is a progressive neurodegenerative disorder which is caused due to repetitive CAG or glutamine expression along the coding region of the Huntington gene. This disease results in certain movement abnormalities, affective disturbances, dementia and cognitive impairments. To this date, there is no proper cure for this rare and fatal neurological condition but there have been certain advancements in the field of genetic animal model research studies to elucidate the understanding of the pathogenesis of this condition. Currently, HD follows a certain therapeutic approach which just relieves the symptoms but doesn't cure the underlying cause of the disease. Stem cell therapy can be a breakthrough in developing a potential cure for this condition. In this review, we have discussed the pathogenesis and the efficacy and clinical practicality of the therapeutic application of stem cell transplantation in Huntington's disease. The application of this groundbreaking therapy on genetically altered animal models has been listed and analyzed in brief.

Immunoinformatics Approach to Design Novel Subunit Vaccine against the Epstein-Barr Virus.

Epstein-Barr virus (EBV) is a lymphotropic virus responsible for numerous epithelial and lymphoid cell malignancies, including gastric carcinoma, Hodgkin's lymphoma, nasopharyngeal carcinoma, and Burkitt lymphoma. Hundreds of thousands of people worldwide get infected with this virus, and in most cases, this viral infection leads to cancer. Although researchers are trying to develop potential vaccines and drug therapeutics, there is still no effective vaccine to combat this virus. In this study, the immunoinformatics approach was utilized to develop a potential multiepitope subunit vaccine against the two most common subtypes of EBV, targeting three of their virulent envelope glycoproteins. Eleven cytotoxic T lymphocyte (CTL) epitopes, 11 helper T lymphocyte (HTL) epitopes, and 10 B-cell lymphocyte (BCL) epitopes were predicted to be antigenic, nonallergenic, nontoxic, and fully conserved among the two subtypes, and nonhuman homologs were used for constructing the vaccine after much analysis. Later, further validation experiments, including molecular docking with different immune receptors (e.g., Toll-like receptors [TLRs]), molecular dynamics simulation analyses (including root means square deviation [RMSD], root mean square fluctuation [RMSF], radius of gyration [Rg], principal-component analysis [PCA], dynamic cross-correlation [DCC], definition of the secondary structure of proteins [DSSP], and Molecular Mechanics Poisson-Boltzmann Surface Area [MM-PBSA]), and immune simulation analyses generated promising results, ensuring the safe and stable response of the vaccine with specific immune receptors after potential administration within the human body. The vaccine's high binding affinity with TLRs was revealed in the docking study, and a very stable interaction throughout the simulation proved the potential high efficacy of the proposed vaccine. Further, in silico cloning was also conducted to design an efficient mass production strategy for future bulk industrial vaccine production. IMPORTANCE Epstein-Barr virus (EBV) vaccines have been developing for over 30 years, but polyphyletic and therapeutic vaccines have failed to get licensed. Our vaccine surpasses the limitations of many such vaccines and remains very promising, which is crucial because the infection rate is higher than most viral infections, affecting a whopping 90% of the adult population. One of the major identifications covers a holistic analysis of populations worldwide, giving us crucial information about its effectiveness for everyone's unique immunological system. We targeted three glycoproteins that enhance the virulence of the virus to design an epitope-based polyvalent vaccine against two different strains of EBV, type 1 and 2. Our methodology in this study is nonconventional yet swift to show effective results while designing vaccines.

Differential gene expression profiling reveals potential biomarkers and pharmacological compounds against SARS-CoV-2: Insights from machine learning and bioinformatics approaches.

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has created an urgent global situation. Therefore, it is necessary to identify the differentially expressed genes (DEGs) in COVID-19 patients to understand disease pathogenesis and the genetic factor(s) responsible for inter-individual variability and disease comorbidities. The pandemic continues to spread worldwide, despite intense efforts to develop multiple vaccines and therapeutic options against COVID-19. However, the precise role of SARS-CoV-2 in the pathophysiology of the nasopharyngeal tract (NT) is still unfathomable. This study utilized machine learning approaches to analyze 22 RNA-seq data from COVID-19 patients (n = 8), recovered individuals (n = 7), and healthy individuals (n = 7) to find disease-related differentially expressed genes (DEGs). We compared dysregulated DEGs to detect critical pathways and gene ontology (GO) connected to COVID-19 comorbidities. We found 1960 and 153 DEG signatures in COVID-19 patients and recovered individuals compared to healthy controls. In COVID-19 patients, the DEG-miRNA, and DEG-transcription factors (TFs) interactions network analysis revealed that E2F1, MAX, EGR1, YY1, and SRF were the highly expressed TFs, whereas hsa-miR-19b, hsa-miR-495, hsa-miR-340, hsa-miR-101, and hsa-miR-19a were the overexpressed miRNAs. Three chemical agents (Valproic Acid, Alfatoxin B1, and Cyclosporine) were abundant in COVID-19 patients and recovered individuals. Mental retardation, mental deficit, intellectual disability, muscle hypotonia, micrognathism, and cleft palate were the significant diseases associated with COVID-19 by sharing DEGs. Finally, the detected DEGs mediated by TFs and miRNA expression indicated that SARS-CoV-2 infection might contribute to various comorbidities. Our results provide the common DEGs between COVID-19 patients and recovered humans, which suggests some crucial insights into the complex interplay between COVID-19 progression and the recovery stage, and offer some suggestions on therapeutic target identification in COVID-19 caused by the SARS-CoV-2.

Coinfection of COVID-19 and Dengue: A Case Report.

While the COVID-19 pandemic takes the world by storm, dengue-endemic regions risk developing a co-epidemic in COVID-19/dengue coinfection. With both infections as causes of high morbidity rates, the potentially fatal outcomes of coinfection are even greater, and several cases are emerging, severe and moderate, showing how common it may become in certain regions. The case reported here shows a 38-year-old male patient with high-grade fever, with complaints of nausea, joint, and muscle aches, all characteristic symptoms of COVID-19 and dengue. Initially suspected of being infected with COVID-19 only, the RT-PCR test of the nasopharyngeal swab confirmed COVID-19 infection, while the positive reactivity to IgG and IgM in the Dengue Duo test revealed a dengue coinfection. Except for the persistent high fever, the Patient's symptoms were not severe, although the tests confirmed the infections to be "moderate to severe" and showed steady and rapid recovery. The tests showed some interesting results, which provided additional research opportunities. Overall, this case report illustrates the existence of coinfections in the Philippines, demonstrating the difficulty in distinguishing the two infections and the need for proper diagnosis, prevention, and management measures.

The Deltacron conundrum: Its origin and potential health risks.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), since its outbreak in December 2019, has been capable of continuing the pandemic by mutating itself into different variants. Mass vaccinations, antibiotic treatment therapy, herd immunity, and preventive measures have reduced the disease's severity from the emerging variants. However, the virus is undergoing recombination among the current two variants: Delta and Omicron, resulting in a new variant, informally known as "Deltacron," which was controversial as it might be a product of lab contamination between Omicron and Delta samples. However, the proclamation was proved wrong, and the experts are putting more effort into better understanding the variant's epidemiological characteristics to control potential outbreaks. This review has discussed the potential mutations in the novel variant and prospective risk factors and therapeutic options in the context of this new variant. This study could be used as a guide for implementing appropriate controls in a sudden outbreak of this new variant.

Insights from a computational analysis of the SARS-CoV-2 Omicron variant: Host-pathogen interaction, pathogenicity, and possible drug therapeutics.

INTRODUCTION: Prominently accountable for the upsurge of COVID-19 cases as the world attempts to recover from the previous two waves, Omicron has further threatened the conventional therapeutic approaches. The lack of extensive research regarding Omicron has raised the need to establish correlations to understand this variant by structural comparisons. Here, we evaluate, correlate, and compare its genomic sequences through an immunoinformatic approach to understand its epidemiological characteristics and responses to existing drugs. METHODS: We reconstructed the phylogenetic tree and compared the mutational spectrum. We analyzed the mutations that occurred in the Omicron variant and correlated how these mutations affect infectivity and pathogenicity. Then, we studied how mutations in the receptor-binding domain affect its interaction with host factors through molecular docking. Finally, we evaluated the drug efficacy against the main protease of the Omicron through molecular docking and validated the docking results with molecular dynamics simulation. RESULTS: Phylogenetic and mutational analysis revealed the Omicron variant is similar to the highly infectious B.1.620 variant, while mutations within the prominent proteins are hypothesized to alter its pathogenicity. Moreover, docking evaluations revealed significant differences in binding affinity with human receptors, angiotensin-converting enzyme 2 and NRP1. Surprisingly, most of the tested drugs were proven to be effective. Nirmatrelvir, 13b, and Lopinavir displayed increased effectiveness against Omicron. CONCLUSION: Omicron variant may be originated from the highly infectious B.1.620 variant, while it was less pathogenic due to the mutations in the prominent proteins. Nirmatrelvir, 13b, and Lopinavir would be the most effective, compared to other promising drugs that were proven effective.

Immunoinformatic Design of a Multivalent Peptide Vaccine Against Mucormycosis: Targeting FTR1 Protein of Major Causative Fungi.

Mucormycosis is a potentially fatal illness that arises in immunocompromised people due to diabetic ketoacidosis, neutropenia, organ transplantation, and elevated serum levels of accessible iron. The sudden spread of mucormycosis in COVID-19 patients engendered massive concern worldwide. Comorbidities including diabetes, cancer, steroid-based medications, long-term ventilation, and increased ferritin serum concentration in COVID-19 patients trigger favorable fungi growth that in turn effectuate mucormycosis. The necessity of FTR1 gene-encoded ferrous permease for host iron acquisition by fungi has been found in different studies recently. Thus, targeting the transit component could be a potential solution. Unfortunately, no appropriate antifungal vaccine has been constructed as of yet. To date, mucormycosis has been treated with antiviral therapy and surgical treatment only. Thus, in this study, the FTR1 protein has been targeted to design a convenient and novel epitope-based vaccine with the help of immunoinformatics against four different virulent fungal species. Furthermore, the vaccine was constructed using 8 CTL, 2 HTL, and 1 LBL epitopes that were found to be highly antigenic, non-allergenic, non-toxic, and fully conserved among the fungi under consideration. The vaccine has very reassuring stability due to its high pI value of 9.97, conclusive of a basic range. The vaccine was then subjected to molecular docking, molecular dynamics, and immune simulation studies to confirm the biological environment's safety, efficacy, and stability. The vaccine constructs were found to be safe in addition to being effective. Finally, we used in-silico cloning to develop an effective strategy for vaccine mass production. The designed vaccine will be a potential therapeutic not only to control mucormycosis in COVID-19 patients but also be effective in general mucormycosis events. However, further in vitro, and in vivo testing is needed to confirm the vaccine's safety and efficacy in controlling fungal infections. If successful, this vaccine could provide a low-cost and effective method of preventing the spread of mucormycosis worldwide.