Search Results (52)

Monkeypox virus (MPXV), which previously caused mainly zoonotic infections, is currently the causative agent of the mpox outbreak that began in 2022. Since the mpox outbreak is characterized by sustained human-to-human transmission, the evolutionary trajectory of MPXV is an important scientific issue. The prevailing hypothesis suggests that the modern orthopoxviruses originated from cowpox-like ancestors with larger genomes that infected a wide range of hosts. Subsequent evolution included the reduction of the genome and the accumulation of substitutions in key proteins. Molecular dating of MPXV evolution revealed 5–6-fold acceleration in the evolutionary rate that was observed in subclade IIb after 2018, reaching 1.8 × 10⁻⁵ substitutions/site/year, likely due to virus’ adaptation to humans. The origin of MPXV from its precursor was primarily driven by the accumulation of non-synonymous substitutions in the key host range genes, including those associated with the protein inhibiting host protein synthesis (OPG173) and host immune evasion (OPG027). The subsequent divergence of MPXV into clades I and II largely depended on mutations in the gene encoding the Bcl-2-like protein. Finally, the division of clade II into subclades IIa and IIb was facilitated by further non-synonymous substitutions in the soluble interferon alpha/beta receptor and hemagglutinin genes. Full article

The paper proposes the exploratory data analysis (EDA) of Monkeypox disease using machine learning approaches. Infection with the Monkeypox virus causes the uncommon illness of Monkeypox. The Monkeypox virus is a member of the Orthopoxvirus genus, which also includes the variola, vaccinia, and cowpox viruses that cause smallpox. To get the most out of the Monkeypox data, there is a need to perform some type of exploratory data analysis (EDA). This is a kind of data analysis that uses visual approaches to examine the data. Statistical summaries and graphical representations are used to detect trends and patterns, or to verify assumptions. In this paper, an exploratory data analysis of Monkeypox cases is performed using machine learning. Firstly, we find the top 10 countries based on confirmed cases, suspected cases, and hospitalized cases. Then, we find the cases with a travel history, cases without a travel history, confirmed Monkeypox cases across the globe, and suspected Monkepox cases across the globe. This will be very helpful for researchers working on machine learning and seeking patterns for Monkeypox to easily predict Monkeypox cases in their country. Full article

Monkeypox virus (MPXV), the pathogen responsible for the infectious disease monkeypox, causes lesions on the skin, lymphadenopathy, and fever. It has posed a global public health threat since May 2022. Highly sensitive and specific detection of MPXV is crucial for preventing the spread of the disease. Pyrococcus furiosus Argonaute (PfAgo) is an artificial DNA-guided restriction cleavage enzyme programmable with 5′-phosphorylated ssDNA sequences, which can be developed to specifically detect nucleic acids of pathogens. Here, a PfAgo-based system was established for the detection of MPXV-specific DNA targeting the F3L gene. A short amplicon of 79 bp could be obtained through a fast PCR procedure, which was completed within 45 min. Two 5′-phosphorylation guide DNAs were designed to guide PfAgo to cleave the amplicon to obtain an 18 bp 5′-phosphorylation sequence specific to MPXV, not to other orthopoxviruses (cowpox, variola, and vaccinia viruses). The 18 bp sequence guided PfAgo to cleave a designed probe specific to MPXV to emit fluorescence. With optimized conditions for the PfAgo-MPXV system, it could be completed in 60 min for the detection of the extracted MPXV DNA with the limit of detection (LOD) of 1.1 copies/reaction and did not depend on expensive instruments. Successful application of the PfAgo-MPXV system in sensitively detecting MPXV in simulated throat swabs, skin swabs, sera, and wastewater demonstrated the system’s good performance. The PfAgo platform, with high sensitivity and specificity established here, has the potential to prevent the spread of MPXV. Full article

Poxviridae is a family of large, complex, enveloped, and double-stranded DNA viruses. The members of this family are ubiquitous and well known to cause contagious diseases in humans and other types of animals as well. Taxonomically, the poxviridae family is classified into two subfamilies, namely Chordopoxvirinae (affecting vertebrates) and Entomopoxvirinae (affecting insects). The members of the Chordopoxvirinae subfamily are further divided into 18 genera based on the genome architecture and evolutionary relationship. Of these 18 genera, four genera, namely Molluscipoxvirus, Orthopoxvirus, Parapoxvirus, and Yatapoxvirus, are known for infecting humans. Some of the popular members of poxviridae are variola virus, vaccine virus, Mpox (formerly known as monkeypox), cowpox, etc. There is still a pressing demand for the development of effective vaccines against poxviruses. Integrated immunoinformatics and artificial-intelligence (AI)-based methods have emerged as important approaches to design multi-epitope vaccines against contagious emerging infectious diseases. Despite significant progress in immunoinformatics and AI-based techniques, limited methods are available to predict the epitopes. In this study, we have proposed a unique method to predict the potential antigens and T-cell epitopes for multiple poxviruses. With PoxiPred, we developed an AI-based tool that was trained and tested with the antigens and epitopes of poxviruses. Our tool was able to locate 3191 antigen proteins from 25 distinct poxviruses. From these antigenic proteins, PoxiPred redundantly located up to five epitopes per protein, resulting in 16,817 potential T-cell epitopes which were mostly (i.e., 92%) predicted as being reactive to CD8+ T-cells. PoxiPred is able to, on a single run, identify antigens and T-cell epitopes for poxviruses with one single input, i.e., the proteome file of any poxvirus. Full article

Smallpox was eradicated in less than 200 years after Edward Jenner’s practice of cowpox variolation in 1796. The forty-three years of us living free of smallpox, beginning in 1979, never truly separated us from poxviruses. The recent outbreak of monkeypox in May 2022 might well warn us of the necessity of keeping up both the scientific research and public awareness of poxviruses. One of them in particular, the vaccinia virus (VACV), has been extensively studied as a vector given its broad host range, extraordinary thermal stability, and exceptional immunogenicity. Unceasing fundamental biological research on VACV provides us with a better understanding of its genetic elements, involvement in cellular signaling pathways, and modulation of host immune responses. This enables the rational design of safer and more efficacious next-generation vectors. To address the new technological advancement within the past decade in VACV research, this review covers the studies of viral immunomodulatory genes, modifications in commonly used vectors, novel mechanisms for rapid generation and purification of recombinant virus, and several other innovative approaches to studying its biology. Full article

Monkeypox (Mpox) is a contagious illness that is caused by the monkeypox virus, which is part of the same family of viruses as variola, vaccinia, and cowpox. It was first detected in the Democratic Republic of the Congo in 1970 and has since caused sporadic cases and outbreaks in a few countries in West and Central Africa. In July 2022, the World Health Organization (WHO) declared a public-health emergency of international concern due to the unprecedented global spread of the disease. Despite breakthroughs in medical treatments, vaccines, and diagnostics, diseases like monkeypox still cause death and suffering around the world and have a heavy economic impact. The 85,189 reported cases of Mpox as of 29 January 2023 have raised alarm bells. Vaccines for the vaccinia virus can protect against monkeypox, but these immunizations were stopped after smallpox was eradicated. There are, however, treatments available once the illness has taken hold. During the 2022 outbreak, most cases occurred among men who had sex with men, and there was a range of 7–10 days between exposure and the onset of symptoms. Three vaccines are currently used against the Monkeypox virus. Two of these vaccines were initially developed for smallpox, and the third is specifically designed for biological-terrorism protection. The first vaccine is an attenuated, nonreplicating smallpox vaccine that can also be used for immunocompromised individuals, marketed under different names in different regions. The second vaccine, ACAM2000, is a recombinant second-generation vaccine initially developed for smallpox. It is recommended for use in preventing monkeypox infection but is not recommended for individuals with certain health conditions or during pregnancy. The third vaccine, LC16m8, is a licensed attenuated smallpox vaccine designed to lack the B5R envelope-protein gene to reduce neurotoxicity. It generates neutralizing antibodies to multiple poxviruses and broad T-cell responses. The immune response takes 14 days after the second dose of the first two vaccines and 4 weeks after the ACAM2000 dose for maximal immunity development. The efficacy of these vaccines in the current outbreak of monkeypox is uncertain. Adverse events have been reported, and a next generation of safer and specific vaccines is needed. Although some experts claim that developing vaccines with a large spectrum of specificity can be advantageous, epitope-focused immunogens are often more effective in enhancing neutralization. Full article

Cowpox viruses (CPXVs) exhibit the broadest known host range among the Poxviridae family and have caused lethal outbreaks in various zoo animals and pets across 12 Eurasian countries, as well as an increasing number of human cases. Herein, we review the history of how the cowpox name has evolved since the 1700s up to modern times. Despite early documentation of the different properties of CPXV isolates, only modern genetic analyses and phylogenies have revealed the existence of multiple Orthopoxvirus species that are currently constrained under the CPXV designation. We further chronicle modern outbreaks in zoos, domesticated animals, and humans, and describe animal models of experimental CPXV infections and how these can help shaping CPXV species distinctions. We also describe the pathogenesis of modern CPXV infections in animals and humans, the geographic range of CPXVs, and discuss CPXV–host interactions at the molecular level and their effects on pathogenicity and host range. Finally, we discuss the potential threat of these viruses and the future of CPXV research to provide a comprehensive review of CPXVs. Full article

The monkeypox disease (MPX) outbreak of 2022 has been reported in more than one hundred countries and is becoming a global concern. Unfortunately, only a few treatments, such as tecovirimat (TCV), are available against MPX. Brincidofovir (BCV) is a United States Food and Drug Administration (USFDA)-approved antiviral against smallpox. This article reviews the potential of BCV for treating MPX and other Orthopoxvirus (OPXVs) diseases. The literature for this review was collected from PubMed, authentic websites (USFDA, Chimerix), and freely available patent databases (USPTO, Espacenet, and Patentscope). BCV (a lipophilic derivative of cidofovir) has been discovered and developed by Chimerix Incorporation, USA. Besides smallpox, BCV has also been tested clinically for various viral infections (adenovirus, cytomegalovirus, ebola virus, herpes simplex virus, and double-stranded DNA virus). Many health agencies and reports have recommended using BCV for MPX. However, no health agency has yet approved BCV for MPX. Accordingly, the off-label use of BCV is anticipated for MPX and various viral diseases. The patent literature revealed some important antiviral compositions of BCV. The authors believe there is a huge opportunity to create novel, inventive, and patentable BCV-based antiviral therapies (new combinations with existing antivirals) for OPXVs illnesses (MPX, smallpox, cowpox, camelpox, and vaccinia). It is also advised to conduct drug interaction (food, drug, and disease interaction) and drug resistance investigations on BCV while developing its combinations with other medications. The BCV-based drug repurposing options are also open for further exploration. BCV offers a promising opportunity for biosecurity against OPXV-based bioterrorism attacks and to control the MPX outbreak of 2022. Full article

Cowpox is caused by a DNA virus known as the cowpox virus (CPXV) belonging to the Orthopoxvirus genus in the family Poxviridae. Cowpox is a zoonotic disease with the broadest host range among the known poxviruses. The natural reservoir hosts of CPXV are wild rodents. Recently, the cases of orthopoxviral infections have been increasing worldwide, and cowpox is considered the most common orthopoxviral infection in Europe. Cowpox is often a self-limiting disease, although cidofovir or anti-vaccinia gammaglobulin can be used in severe and disseminated cases of human cowpox. In this computational study, a molecular docking analysis of thymine- and arabinofuranosyl-thymine-related structures (1–21) on two cowpox-encoded proteins was performed with respect to the cidofovir standard and a 3D ligand-based pharmacophore model was generated. Three chemical structures (PubChem IDs: 123370001, 154137224, and 90413364) were identified as potential candidates for anti-cowpox agents. Further studies combining in vitro and in silico molecular dynamics simulations to test the stability of these promising compounds could effectively improve the future design of cowpox virus inhibitors, as molecular docking studies are not sufficient to consider a ligand a potential drug. Full article

Despite the fact that the variola virus is considered eradicated, the search for new small molecules with activity against orthopoxviruses remains an important task, especially in the context of recent outbreaks of monkeypox. As a result of this work, a number of amides of benzoic acids containing an adamantane fragment were obtained. Most of the compounds demonstrated activity against vaccinia virus, with a selectivity index SI = 18,214 for the leader compound 18a. The obtained derivatives also demonstrated activity against murine pox (250 ≤ SI ≤ 6071) and cowpox (125 ≤ SI ≤ 3036). A correlation was obtained between the IC₅₀ meanings and the binding energy to the assumed biological target, the p37 viral protein with R² = 0.60. Full article

Amidst the ongoing monkeypox outbreak, global awareness has been directed towards the prevention of viral transmission and case management, with the World Health Organization declaring the outbreak a public health emergency of international concern. Monkeypox virus is one of several species in the Orthopoxvirus genus, with other species of the genus including the variola, cowpox, mousepox, camelpox, raccoonpox, skunkpox, and volepox viruses. Although the nomenclature of these species is based on the animal host from which they were originally isolated, transmission from animals to humans has been reported with several species. The progression of disease, following an incubation period, typically consists of a prodromal phase with systemic flu-like symptoms. Various organ systems may be affected in addition to the formation of pathognomonic skin lesions. As monkeypox poses a continued public health concern, the ophthalmic sequelae of monkeypox virus, especially those leading to vision loss, warrant consideration as well. This review provides a comprehensive summary of the ophthalmic implications of poxviruses in clinical and laboratory settings reported in the literature, as well as areas of unmet need and future research. Full article

Southeast Asia is considered a global hotspot of emerging zoonotic diseases. There, wildlife is commonly traded under poor sanitary conditions in open markets; these markets have been considered ‘the perfect storm’ for zoonotic disease transmission. We assessed the potential of wildlife trade in spreading viral diseases by quantifying the number of wild animals of four mammalian orders (Rodentia, Chiroptera, Carnivora and Primates) on sale in 14 Indonesian wildlife markets and identifying zoonotic viruses potentially hosted by these animals. We constructed a network analysis to visualize the animals that are traded alongside each other that may carry similar viruses. We recorded 6725 wild animals of at least 15 species on sale. Cities and markets with larger human population and number of stalls, respectively, offered more individuals for sale. Eight out of 15 animal taxa recorded are hosts of 17 zoonotic virus species, nine of which can infect more than one species as a host. The network analysis showed that long-tailed macaque has the greatest potential for spreading viral diseases, since it is simultaneously the most traded species, sold in 13/14 markets, and a potential host for nine viruses. It is traded alongside pig-tailed macaques in three markets, with which it shares six viruses in common (Cowpox, Dengue, Hepatitis E, Herpes B, Simian foamy, and Simian retrovirus type D). Short-nosed fruit bats and large flying foxes are potential hosts of Nipah virus and are also sold in large quantities in 10/14 markets. This study highlights the need for better surveillance and sanitary conditions to avoid the negative health impacts of unregulated wildlife markets. Full article

At the time the world is attempting to get over the damage caused by the COVID-19 spread, the monkeypox virus threatens to evolve into a global pandemic. Human monkeypox was first recognized in Africa and has recently emerged in 103 countries outside Africa. However, monkeypox diagnosis in an early stage is difficult because of the similarity between it, chickenpox, cowpox and measles. In some cases, computer-assisted detection of monkeypox lesions can be helpful for quick identification of suspected cases. Infected and uninfected cases have added to a growing dataset that is publicly accessible and may be utilized by machine and deep learning to predict the suspected cases at an early stage. Motivated by this, a diagnostic framework to categorize the cases of patients into four categories (i.e., normal, monkeypox, chicken pox and measles) is proposed. The diagnostic framework is a hybridization of pre-trained Convolution Neural Network (CNN) models, machine learning classifiers and a metaheuristic optimization algorithm. The hyperparameters of the five pre-trained models (i.e., VGG19, VGG16, Xception, MobileNet and MobileNetV2) are optimized using a Harris Hawks Optimizer (HHO) metaheuristic algorithm. After that, the features can be extracted from the feature extraction and reduction layers. These features are classified using seven machine learning models (i.e., Random Forest, AdaBoost, Histogram Gradient Boosting, Gradient Boosting, Support Vector Machine, Extra Trees and KNN). For each classifier, 10-fold cross-validation is used to train and test the classifiers on the features and the weighted average performance metrics are reported. The predictions from the pre-trained model and machine learning classifiers are then processed using majority voting. This study conducted the experiments on two datasets (i.e., Monkeypox Skin Images Dataset (MSID) and Monkeypox Images Dataset (MPID)). MSID dataset values 97.67%, 95.19%, 97.96%, 95.11%, 96.58%, 95.10%, 90.93% and 96.65% are achieved concerning accuracy, sensitivity, specificity, PPV, BAC, F1, IoU and ROC, respectively. While for the MPID dataset, values of 97.51%, 94.84%, 94.48%, 94.96%, 96.66%, 94.88%, 90.45% and 96.69% are achieved concerning accuracy, sensitivity, specificity, PPV, BAC, F1, IoU and ROC, respectively. Full article

The aim of the work was an experimental evaluation of the characteristics of the kit for the rapid immunochemical detection of orthopoxviruses (OPV). The kit is based on the method of one-stage dot-immunoassay on flat protein arrays using gold conjugates and a silver developer. Rabbit polyclonal antibodies against the vaccinia virus were used as capture and detection reagents. The sensitivity of detection of OPV and the specificity of the analysis were assessed using culture crude preparations (monkeypox virus, vaccinia virus, rabbitpox virus, cowpox virus, and ectromelia virus), a suspension from a crust from a human vaccination site as well as blood and tissue suspensions of infected rabbits. It has been shown that the assay using the kit makes it possible to detect OPV within 36 min at a temperature of 18–40 °C in unpurified culture samples of the virus and clinical samples in the range of 10³–10⁴ PFU/mL. Tests of the kit did not reveal cross-reactivity with uninfected cell cultures and viral pathogens of exanthematous infections (measles, rubella and chicken pox). The kit can be used to detect or exclude the presence of a virus threat in samples and can be useful in various aspects of biosecurity. The simplicity of analysis, the possibility of visual accounting the and interpretation of the results make it possible to use the test in laboratories with a high level of biological protection and in out-of-laboratory conditions. Full article

The uncommon illness known as monkeypox is brought on by the monkeypox virus. The Orthopoxvirus genus belongs to the family Poxviridae, which also contains the monkeypox virus. The variola virus, which causes smallpox; the vaccinia virus, which is used in the smallpox vaccine; and the cowpox virus are all members of the Orthopoxvirus genus. There is no relationship between chickenpox and monkeypox. After two outbreaks of a disorder resembling pox, monkeypox was first discovered in colonies of monkeys kept for research in 1958. The illness, also known as “monkeypox”, still has no known cause. However, non-human primates and African rodents can spread the disease to humans (such as monkeys). In 1970, a human was exposed to monkeypox for the first time. Several additional nations in central and western Africa currently have documented cases of monkeypox. Before the 2022 outbreak, almost all instances of monkeypox in people outside of Africa were connected to either imported animals or foreign travel to nations where the illness frequently occurs. In this work, the most recent monkeypox dataset was evaluated and the significant instances were visualized. Additionally, nine different forecasting models were also used, and the prophet model emerged as the most reliable one when compared with all nine models with an MSE value of 41,922.55, an R² score of 0.49, a MAPE value of 16.82, an MAE value of 146.29, and an RMSE value of 204.75, which could be considerable assistance to clinicians treating monkeypox patients and government agencies monitoring the origination and current state of the disease. Full article