Search Results (384)

Human monkeypox (Mpox) is a zoonotic disease caused by the Monkeypox virus (MPXV). As of 14 August 2024, the World Health Organization (WHO) has declared it a global health emergency. For Mpox, this was the second public health emergency of global significance in the past two years. MPXV belongs to the Poxviridae family and is phylogenetically and epidemically divided into two clades: the Congo Basin (Clade-I) and the West African (Clade-II) clades. Clade-I has been associated with more severe disease progression and higher mortality compared to Clade-II, and thus the differentiation between clades can play an important role in predicting disease prognosis. The LAMP technique has the advantages of not requiring thermal cycling and achieving higher amplification in a shorter time compared to qPCR. Different types of LAMP assays were developed in this study to benefit from these advantages. We report the development of LAMP-1 and LAMP-2 assays using the LAMP method to detect MPXV Clade-I and Clade-II, respectively. The LAMP-1 assay includes both fluorescence and visible colorimetric readout tests developed with sensitivities of 10³ and 10⁷ copies, respectively. For the LAMP-2 assay, a probe-based test utilizing the Novel R-Duplex DARQ probe was developed, offering fluorescence detection at a sensitivity of 10³ copies. As a result, we successfully developed three highly specific molecular diagnostic tests that distinctly differentiate between MPXV clades, delivering essential tools for the precise diagnosis and effective control of Mpox. Full article

Monkeypox (MPOX) is a zoonotic viral disease caused by the Monkeypox virus (MPXV), which has become the most significant public health threat within the Orthopoxvirus genus since the eradication of the Variola virus (VARV). Despite the extensive attention MPXV has garnered, little is known about its clinical manifestations in humans. In this study, a high-throughput RNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was employed to investigate the transcriptional and metabolic responses of HEK293T cells to the MPXV A5L protein. RNA-seq analysis identified a total of 1473 differentially expressed genes (DEGs), comprising 911 upregulated and 562 downregulated genes. Additionally, LC-MS/MS analysis revealed 185 cellular proteins with significantly altered abundance ratios that interact with the A5L protein. Here, we perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the transcriptome and proteome signatures of MPXV A5L-expressing HEK293T cells to gain insights into the virus proteins-host interplay. Transcriptomic analysis revealed that transfection of the MPXV A5L protein modulated genes primarily associated with the cell cycle, ribosome, and DNA replication. Proteomic analysis indicated that this protein predominantly interacted with host ribosomal proteins and cytoskeletal proteins. The combination of transcriptomic and proteomic analysis offers new perspectives for understanding the interaction between pathogens and hosts. Our research emphasizes the significant role of MPXV A5L in facilitating viral internalization and assembly, as well as its impact on the host’s translation system. Full article

Monkeypox (mpox) is a viral infection closely related to smallpox, manifesting as a milder febrile rash in affected individuals. Over the past two decades, the incidence of mpox has surged, possibly linked to a declining immunity against the smallpox vaccine worldwide. Recent outbreaks of mpox in multiple countries have sparked concerns regarding altered transmission patterns and the potential for a global menace. In this article, we present a multidimensional review encompassing the latest scientific discoveries, illuminating the intricate structure of the human mpox virus. Key findings include advancements in understanding the virus’s molecular mechanisms, which highlight its genetic adaptability and potential for zoonotic spillover. Diagnostic innovations, such as improved molecular assays, have enhanced detection accuracy, while novel therapeutic strategies, including antiviral drugs and vaccines, show promise in mitigating outbreaks. Our conclusions emphasize the importance of robust surveillance systems, vaccination programs, and rapid response strategies to curb mpox’s spread. Future recommendations include strengthening global collaboration for zoonotic disease surveillance, advancing the research on host–pathogen interactions, and developing next-generation therapeutics to address this emerging public health threat effectively. Full article

Heterologous protein expression often faces significant challenges, particularly when the target protein has posttranslational modifications, is toxic, or is prone to misfolding. These issues can result in low expression levels, aggregation, or even cell death. Such problems are exemplified by the expression of phospholipase p37, a critical target for chemotherapeutic drugs against pathogenic human orthopoxviruses, including monkeypox and smallpox viruses. The complex structure and broad enzymatic activity of phospholipase p37 render it toxic to host cells, necessitating specialized strategies for heterologous expression. In our study, we addressed these challenges using the vaccinia virus F13 protein as a model. We demonstrated that p37 can be effectively synthesized in E. coli as a GST fusion protein by co-expressing it with the GroEL/ES chaperone system and Trigger Factor chaperone. Full article

Background/Objectives: Since 2022, outbreaks of monkeypox have raised widespread concern and have been declared a public health emergency of international concern by the World Health Organization. There is an urgent need to develop a safe and effective vaccine against the monkeypox virus (MPXV). Recombinant protein vaccines play a significant role in the prevention of infectious diseases due to their high safety and efficacy. Methods: We used the A29, E8, M1, A35, and B6 proteins of MPXV as candidate antigens to generate a panel of multi-component MPXV vaccine candidates, which were administered subcutaneously to immunize mice. Results: The results showed that the vaccine candidates Mix-AEM, Mix-AEMA, Mix-AEMB, and Mix-AEMAB effectively elicited strong neutralizing antibody responses and demonstrated significant protection against vaccinia virus (VACV) infection in a murine model. The vaccine candidate Mix-AEM induced significantly higher levels of neutralizing antibodies, cellular immunity capacity, and virus clearance compared to the vaccine candidate Mix-AE (lacking M1). Single-component immunization showed that M1 induced higher levels of neutralizing antibodies than A29 and E8. These results indicated that M1 is a critical and essential antigen in the MPXV vaccine. The number of cells secreting IFN-γ was significantly increased in the Mix-AEMA and Mix-AEMAB groups compared to the A35-deficient vaccine candidates, demonstrating the important role of A35 in inducing IFN-γ secreting. In addition, the neutralizing antibodies induced by these multi-component vaccine candidates were maintained at high levels six months after the third immunization. Conclusions: In summary, this study lays the groundwork for combining antigens to develop multi-component subunit vaccines. Full article

Monkeypox (Mpox) is an infectious disease caused by the Mpox virus belonging to the Orthopoxvirus genus in the Poxviridae family and has been declared by the WHO as a global health emergency owing to its rapid spread during 2022 and 2023. All patients diagnosed with Mpox who were confirmed by PCR between July 2022 and April 2023 were included in this study. In total, 405 patients in whom clade 2 was identified were included. Notably, 99% of included patients were men, with 82% of them aged 20–39 years. Furthermore, 71% were men who had sex with men, and 34% were HIV carriers. Regarding the morphology of the lesions, approximately 63% presented with papulonecrotic rash, which sometimes alternated with pustules depending on the stage they were in. All patients presented with systemic symptoms. Five patients required hospital admission, one of whom died, and presented with HIV and severe immunosuppression. Clinical findings suggest that contact during sexual intercourse is the most likely transmission mechanism and genital involvement is the most frequent clinical form. HIV was the primary comorbidity. Genital lesions were common, especially in vulnerable populations such as those who engage in high-risk sexual behaviors. Full article

Background and Aim: Monkeypox (Mpox) is a viral disease mainly found in central and western Africa, with symptoms similar to variola virus (smallpox) but distinguished by the early lymph node swelling specific to Mpox. This review summarizes the neuropsychiatric manifestations of Mpox infection and vaccination, along with management approaches. Method: We searched different databases such as PubMed, Scopus, WoS, and Google Scholar about the neuropsychiatric manifestations of Mpox disease and the associated strategies of management. Results and conclusions: Mpox can cause a wide range of neurological symptoms. These range from mild symptoms like headaches, muscle aches, fatigue, and pain to severe symptoms, including seizures, blindness, photophobia, delirium, coma, encephalitis, and transverse myelitis. It is essential to distinguish Mpox from smallpox and other orthopox viruses. Psychiatric issues, such as stigma, disfigurement, isolation, and physical pain, are common in Mpox patients. To address these, healthcare providers should provide accurate information, counseling, and virtual support. Neurological side effects were associated with the previous smallpox vaccine, which offered cross-protection against Mpox. This vaccine has since been replaced by JYNNEOS, which does not pose any neurological risks. Mpox-related neurological symptoms are generally managed with supportive care, including NSAIDs, antibiotics, antiepileptics, and sedatives for seizures. Antivirals like acyclovir are also used. Severe cases may require hospitalization or intubation. So, we recommend early diagnosis, isolation, and prompt treatment, as Mpox spreading to the central nervous system can lead to serious and potentially fatal complications. Full article

Background/Objectives: Monkeypox is a re-emerging viral disease with features of infectiously transmitted zoonoses. It is now considered a public health priority because of its rising incidence and transmission from person to person. Monkeypox virus (MPXV) VP39 protein is identified as an essential protein for replication of the virus, and therefore, it is a potential target for antiviral drugs. Methods: This work analyzes the binding affinities and the differential conformational stability of three target compounds and one control compound with the VP39 protein through multiple computational methods. Results: The re-docking analysis revealed that the compounds had high binding affinities towards the target protein; among these compounds, compounds 1 and 2 showed the highest binding energies in the virtual screening, and thus, these were considered as the most active inhibitor candidates. Intermolecular interaction analysis revealed distinct binding mechanisms. While compound 1 had very strong hydrogen bonds and hydrophobic interactions, compound 2 had numerous water-mediated interactions, and compound 3 had only ionic and hydrophobic contacts. In molecular dynamic simulations, compounds 1 and 2 showed that the protein–ligand complexes had a stable conformation, with protein RMSD values around 2 Å for both compounds. In contrast, compound 3 was slightly flexible, and the control compound was more flexible. MM/GBSA analysis again supported these results, which gave the binding free energies that were also supportive for these compounds. Conclusions: Notably, all the selected compounds, especially compounds 1 and 2, demonstrate high binding affinity. Therefore, these compounds can be further tested as antiviral agents against monkeypox treatment. Full article

Despite the growing body of evidence addressing the reasons behind vaccine hesitancy, the positive role of media as a key environmental factor influencing vaccination, as well as its function in publicizing and encouraging vaccination, has been less thoroughly explored. This study focuses on the context of the current Monkeypox epidemic, examining the influence of media release channels and message framing on the public’s willingness to receive the Monkeypox vaccine. The findings are empirically validated through a survey experiment conducted in China. The study reveals that both media channels—traditional TV media, official online media, and user-generated media—and media content framings, specifically thematic and episodic, significantly impact the public’s willingness to be vaccinated against Monkeypox. Notably, in the context of this public health event, individuals were more inclined to trust the episodic framing of traditional TV media and the thematic framing of official online media. Compared to thematic framing, episodic framing generally enhances respondents’ willingness to vaccinate. Furthermore, user-generated media exhibited a more negative effect on vaccination intentions during the Monkeypox epidemic, particularly when combined with episodic framing. Heterogeneity analysis indicated a significant difference in the effectiveness of official online media based on audience identity (student vs. non-student), with the student group showing a preference for official online media channels. The findings underscore the importance of public health communication in carefully selecting media release types and message framings. Additionally, it is crucial to consider audience heterogeneity and to employ differentiated communication methods to enhance the effectiveness of vaccine promotion. Full article

The 2022–2023 mpox outbreak exhibited an uneven global distribution. While countries such as the UK, Brazil, and the USA were most heavily affected in 2022, many Asian countries, specifically China, Japan, South Korea, and Thailand, experienced the outbreak later, in 2023, with significantly fewer reported cases relative to their populations. This variation in timing and scale distinguishes the outbreaks in these Asian countries from those in the first wave. This study evaluates the predictability of mpox outbreaks with smaller case counts in Asian countries using popular epidemic forecasting methods, including the ARIMA, Prophet, GLM, GAM, n-Sub-epidemic, and Sub-epidemic Wave frameworks. Despite the fact that the ARIMA and GAM models performed well for certain countries and prediction windows, their results were generally inconsistent and highly dependent on the country, i.e., the dataset, as well as the prediction interval length. In contrast, n-Sub-epidemic Ensembles demonstrated more reliable and robust performance across different datasets and predictions, indicating the effectiveness of this model on small datasets and its utility in the early stages of future pandemics. Full article

Background/Objectives:The emergence of monkeypox outside its endemic region in Africa has raised significant concerns within the public health community due to its rapid global dissemination. Early clinical differentiation of monkeypox from similar diseases, such as chickenpox and measles, presents a challenge. The Monkeypox Skin Lesion Dataset (MSLD) used in this study comprises monkeypox skin lesions, which were collected primarily from publicly accessible sources. The dataset contains 770 original images captured from 162 unique patients. The MSLD includes four distinct class labels: monkeypox, measles, chickenpox, and normal. Methods: This paper presents an ensemble model for classifying the monkeypox dataset, which includes transformer models and support vector machine (SVM). The model development process begins with an evaluation of seven convolutional neural network (CNN) architectures. The proposed model is developed by selecting the top four models based on evaluation metrics for performance. The top four CNN architectures, namely EfficientNetB0, ResNet50, MobileNet, and Xception, are used for feature extraction. The high-dimensional feature vectors extracted from each network are then concatenated and optimized before being inputted into the SVM classifier. Results: The proposed ensemble model, in conjunction with the SVM classifier, achieves an accuracy of 95.45b%. Furthermore, the model demonstrates high precision (95.51%), recall (95.45%), and F1 score (95.46%), indicating its effectiveness in identifying monkeypox lesions. Conclusions: The results of the study show that the proposed hybrid framework achieves robust diagnostic performance in monkeypox detection, offering potential utility for enhanced disease monitoring and outbreak management. The model’s high diagnostic accuracy and computational efficiency indicate that it can be used as an additional tool for clinical decision support. Full article

The monkeypox outbreak has grown beyond the regions in which it was considered endemic. It has spread from central and west Africa to non-endemic regions like Europe, America, and other parts of the world. It has recently been classified as a public health emergency of international concern. This study evaluated the challenges faced globally and equitable access to monkeypox vaccines. Global competition has been observed in the race to obtain vaccines, with low- and middle-income countries being disadvantaged. Great inequity exists in the distribution of vaccines globally through advance purchase agreements, vaccine stockpiling, vaccine nationalism, the inequitable distribution of existing resources, and insufficient surveillance and reporting mechanisms. To address some of these challenges, there is a need for strengthening the global vaccine manufacturing capacity, targeting countries with elevated risk profiles and limited resources, strengthening surveillance systems, and addressing vaccine hesitancy. Full article

Background: The WHO classified the mpox outbreak as a worldwide health emergency. Increasing the contribution of healthcare providers, such as pharmacists, can enhance preventive efforts. Assessing the knowledge and confidence levels of pharmacists in diagnosing and managing mpox cases can shape the response strategies necessary for the management of such outbreaks. Methods: This research employed a cross-sectional survey designed to assess the knowledge and preparedness of pharmacy students and pharmacists in the United Arab Emirates (UAE) regarding the mpox virus outbreak. Independent researchers evaluated the survey items to confirm the face and content validity of the developed survey. The final study’s survey was structured into three distinct sections, each addressing a specific area of interest. Data were analyzed using the IBM SPSS Statistics. Results: The 388 participants had a median age of 22.00 years (IQR = 5.00). The survey revealed that participants primarily relied on the WHO reports for mpox information (79.8%). The total knowledge scores (TK score) varied, ranging from −6 to 23 (median = 6.00), and symptom knowledge scores (SK score) ranged from −3 to 9 (median = 2.00). Older participants (p-value = 0.008) and females (p-value = 0.014) exhibited significantly higher TK scores. Only about 31.0% of participants expressed confidence in diagnosing mpox cases, and 34.6% expressed confidence in managing mpox cases. Nearly a quarter of the participants (24.5%) thought that getting vaccinated against COVID-19 led to contracting mpox more likely, whereas 45.7% believed that a previous infection with COVID-19 increases the risk of having mpox and its associated symptoms. Many respondents (38.7%) expressed their concern that mpox could emerge as the next major epidemic following COVID-19. Conclusion: Although pharmacists and pharmacy students in the UAE are aware of mpox, their knowledge and confidence levels in diagnosing and managing vary significantly. These findings suggest the need for targeted educational programs to enhance the understanding and preparedness of pharmacists to manage and prevent mpox cases. Full article

Ongoing outbreaks and often rapid spread of infections caused by coronaviruses, influenza, Nipah, Dengue, Marburg, monkeypox, and other viruses are a concern for health authorities in most countries. Therefore, the search for and study of new antiviral compounds are in great demand today. Since almost all viruses with pandemic potential have immunotoxic properties of various origins, particular attention is paid to the search and development of immunomodulatory drugs. We have synthesised a new compound related to indole-3-carboxylic acid derivatives (hereinafter referred to as the XXV) that has antiviral and interferon-inducing activity. The purpose of this work is to study the effect of the XXV on the stimulation of the expression of toll-like receptor genes, interferons, and immunoregulatory cytokines in a macrophage-like cell model. In this study, real-time PCR methods were used to obtain data on the transcriptional activity of genes in macrophage-like cells. Stimulation of the genes of toll-like receptors TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 was detected. A high-fold increase in stimulation (from 6.5 to 16,000) of the expression of the TLR3 and TLR4 genes was detected after 4 h of exposure to the XXV. Increased activity of interferon (IFNA1, IFNA2, IFNB1, IFNK, and IFNλ1) genes with simultaneous stimulation of the expression of interferon receptor (IFNAR1 and IFNAR2) genes and signalling molecule (JAK1 and ISG15) genes was detected. Increased fold stimulation of the expression of the cytokine genes IL6, TNFA, IL12A, and IL12B was also observed. Thus, it is shown that the XXV is an activator of TLR genes of innate immunity, which trigger signalling mechanisms of pathogen “recognition” and lead to stimulation of the expression of genes of proinflammatory cytokines and interferons. Full article

In recent years, there have been frequent global outbreaks of viral epidemics such as Zika, COVID-19, and monkeypox, which have had a huge impact on human health and society and have also spurred innovation in virus engineering technology. The rise of synthetic virus genome technology has provided researchers with a new platform to accelerate vaccine and drug development. Although DNA synthesis technology has made significant progress, the current virus genome synthesis technology still requires the assembly of short oligonucleotides of around 60 bp into kb-level lengths when constructing long segments, a process in which the commonly used polymerase chain reaction assembly (PCA) technology has high error rates and is cumbersome to operate. This study optimized the error correction conditions after PCA assembly, increasing the accuracy of synthesizing 1 kb DNA fragments from 4.2 ± 2.1% before error correction to 31.3 ± 3.1% after two rounds of correction, an improvement of over 6 times. This study provides a more efficient operational process for synthesizing virus genomes from scratch, indicating greater potential for virus engineering in epidemic prevention and control and the field of biomedicine. Full article