Monkeypox Virus Research Articles

Ocular manifestations of Monkeypox virus (MPXV) infection with viral persistence in ocular samples: A case series

ObjectiveWe describe the clinical presentation and ocular viral dynamics in patients with Monkeypox virus-related ophthalmic disease (MPXROD). MethodsIn this case series, we investigated five consecutive patients with confirmed mpox, diagnosed through a positive Monkeypox virus (MPXV) Polymerase Chain Reaction (PCR) test and presenting with ocular symptoms. They were referred from the Reference Center for Sexually Transmitted Infections in São Paulo (CRT) to the Uveitis Sector at the Federal University of São Paulo, between August and December 2022. We performed PCR testing on ocular samples and culture supernatants for MPXV in all patients. Viral sequencing was conducted in one of the cases. ResultsReplicating MPXV was identified in at least one ocular sample of all patients, between day 31 and day 145 after the onset of skin lesions. All patients presented with keratitis, 3 with uveitis (60%) and two exhibited hypopyon (40%). The onset of ocular symptoms occurred at a mean of 21.2 days after the appearance of the first skin lesion and persisted, on average, for 61,.6 days, with a worsening trend observed until the initiation of tecovirimat treatment. Tecovirimat treatment was administered to all patients, with initiation occurring between 31 and 145 days after the onset of skin lesions. MPXV genome sequencing of an isolate from one patient classified it as belonging to lineage B1 in clade IIb. ConclusionThis study reveals a late onset and persistence of sight threatening ocular disease, along with potential viral infectivity even after systemic resolution in mpox cases. These findings highlight the risk of ongoing transmission from individuals with prolonged ocular manifestations, particularly through ocular discharge.

Dynamical behavior of fractal-fractional order monkeypox virus model

A virus that infects both humans and animals, monkeypox is common in many West African countries and has sporadically spread to other parts of the world. There are serious public health concerns around the globe as a result of the recent spike in cases of monkeypox among both endemic and non-endemic populations. This paper proposes to use the Caputo sense of fractal fractional-order derivatives to examine the dynamics of monkeypox transmission. The study uses Schauder’s fixed point theorem to evaluate the solutions qualitatively and establish their uniqueness inside the model. The next generation matrix technique is used to compute the essential reproduction number. The stability of equilibrium points is further investigated in the research, and a sensitivity analysis of model parameters is carried out. When the basic reproduction number R0 is less than 1, the equilibrium without infections is locally stable. Also, when R0 exceeds 1, this equilibrium becomes unstable. The proposed model incorporates Ulam–Hyers stability through nonlinear functional analysis. To estimate solutions for the fractal-fractional order monkeypox model, the Lagrange’s interpolation method is utilized. In addition, numerical simulations are carried out to examine the influence of some parameters on the overall dynamics of the model. Numerical simulations are performed using MATLAB software to exemplify the model behavior in the context of the Nigerian case study. The graphical representations suggest that the fractal fractional order affects the dynamics of the monkeypox. The findings indicate that isolation of infected individuals in the human population helps to reduce disease transmission.

Sinefungin analogs targeting VP39 methyltransferase as potential anti-monkeypox therapeutics: a multi-step computational approach.

The increasing spread of the Monkeypox virus (MPXV) presents a significant public health challenge, emphasising the urgent requirement for effective treatments. Our study focuses on the VP39 Methyltransferase enzyme of MPXV as a critical target for therapy. By utilising virtual screening, we investigated natural compounds with structural similarities to sinefungin, a broad-acting MTase inhibitor. From an initial set of 177 compounds, we identified three promising compounds-CNP0346326, CNP0343532, and CNP008361, whose binding scores were notably close to that of sinefungin. These candidates bonded strongly to the VP39 enzyme, hinting at a notable potential to impede the virus. Our rigorous computational assays, including re-docking, extended molecular dynamics simulations, and energetics analyses, validate the robustness of these interactions. The data paint a promising picture of these natural compounds as front-runners in the ongoing race to develop MPXV therapeutics and set the stage for subsequent empirical trials to refine these discoveries into actionable medical interventions.

Designing a smallpox B-cell and T-cell multi-epitope subunit vaccine using a comprehensive immunoinformatics approach.

In this work, we designed a vaccine with a cluster of multiple T-cell/B-cell epitopes, which should be effective in inducing systematic immune responses against variola virus infection. Besides, this work also provides a reference in vaccine design for preventing monkeypox virus infection, which is currently prevalent.

Epidemiological Aspects and Basic Directions of the Protective Medications against Monkeypox Development

Relevance. After smallpox eradication, in conditions of population immunity to orthopoxviruses absence, Monkeypox virus became most significant orthopoxvirus, pathogenic for humans. Therefore the generalization of data on the areas of infection outbreaks, human diseases and methods of prevention and treatment of monkey pox is important task. Aim. To characterize the problem of monkeypox in the world based on an analysis of foreign scientific publications over the past 20 years. Materials and methods. The work used publications presented in the main international medical information databases PubMed, Web of Science, Embase, etc. To analyze the publications, the analytical epidemiological method was used. Results and discussion. Monkeypox virus, obtained and identified in 1958, by genetic and phenotypic differences divides on two clades: West-African with lethality 3.6% and Central-African (Congo Basin) with lethality 10%. Monkeypox virus transmission to men happens in two ways, either from animal-to-human or human-to-human. Monkey pox is endemic only on African continent, but In 2003 year the first outbreak, numbering 47 confirmed cases, was occurred in non-endemic country – USA and the largest monkeypox outbreak began in Nigeria in September 2017 year and continue to the present. Comparison of the genome sequences of strains, isolated from patients in non-endemic countries, showed, that it genetically close to West-african strains, belong to II clades and were descended from a common ancestor. Many cases of disease in humans in the current outbreak have been traced to sexual transmission especially among men, who identify ourselves as gay or bisexual. The basis method for identification of agent in present time is PCR-RT targeting on the tumor necrosis factor (TNF) receptor gene. Usually monkeypox of human is mild, self-limiting disease. The symptoms of monkeypox are varied and non-specific. One of the most frequently observed clinical symptoms is lymphadenopathy. Most patients recover during some weeks. However, specific antiviral treatment – tecovirimat (S-246) and brincidofovir (CMX-001) – may be used for seriously ill or immunocompromised individuals. For prophylactic disease in present time are use vaccines JYNNEOSTM, ACAM2000R and Aventis Pasteur (APSV). Conclusion. General vaccination against monkeypox don't develop accordingly to modern recommendations WHO. Ring vaccination is recommended to conduct for suppression of spread virus in nidus of infection among population. Timely international coordination is needed to prevent the global spread of a disease with epidemic potential.

Optical biosensing of monkeypox virus using novel recombinant silica-binding proteins for site-directed antibody immobilization

The efficient immobilization of capture antibodies is crucial for timely pathogen detection during global pandemic outbreaks. Therefore, we proposed a silica-binding protein featuring core functional domains (cSP). It comprises a peptide with a silica-binding tag designed to adhere to silica surfaces and tandem protein G fragments (2C2) for effective antibody capture. This innovation facilitates precise site-directed immobilization of antibodies onto silica surfaces. We applied cSP to silica-coated optical fibers, creating a fiber-optic biolayer interferometer (FO-BLI) biosensor capable of monitoring the monkeypox virus (MPXV) protein A29L in spiked clinical samples to rapidly detect the MPXV. The cSP-based FO-BLI biosensor for MPXV demonstrated a limit of detection (LOD) of 0.62 ng/mL in buffer, comparable to the 0.52 ng/mL LOD achieved using a conventional streptavidin (SA)-based FO-BLI biosensor. Furthermore, it achieved LODs of 0.77 ng/mL in spiked serum and 0.80 ng/mL in spiked saliva, exhibiting no cross-reactivity with other viral antigens. The MPXV detection process was completed within 14 min. We further proposed a cSP-based multi-virus biosensor strategy capable of detecting various pandemic strains, such as MPXV, the latest coronavirus disease (COVID) variants, and influenza A protein, to extend its versatility. The proposed cSP-modified FO-BLI biosensor has a high potential for rapidly and accurately detecting MPXV antigens, making valuable contributions to epidemiological studies.

Design of multi-epitope chimeric vaccine against Monkeypox virus and SARS-CoV-2: A vaccinomics perspective.

The current era we experience is full with pandemic infectious agents that no longer threatens the major local source but the whole globe. Almost the most emerging infectious agents are severe acute respiratory syndrome coronavirus-2 (SARS CoV-2), followed by monkeypox virus (MPXV). Since no approved antiviral drugs nor licensed active vaccines are yet available, we aimed to utilize immunoinformatics approach to design chimeric vaccine against the two mentioned viruses. This is the first study to deal with design divalent vaccine against SARS-CoV-2 and MPXV. ORF8, E and M proteins from Omicron SARS-CoV-2 and gp182 from MPXV were used as the protein precursor from which multi-epitopes (inducing B-cell, helper T cells, cytotoxic T cells and interferon-ɣ) chimeric vaccine was contrived. The structure of the vaccine construct was predicted, validated, and docked to toll-like receptor-2 (TLR-2). Moreover, its sequence was also used to examine the immune simulation profile and was then inserted into the pET-28a plasmid for in silico cloning. The vaccine construct was probable antigen (0.543) and safe (non-allergen) with strong binding energy to TLR-2 (-1169.8 kcal/mol) and found to have significant immune simulation profile. In conclusion, the designed chimeric vaccine was potent and safe against SARS-CoV-2 and MPXV, which deserves further consideration.

Third-generation smallpox vaccines induce low-level cross-protecting neutralizing antibodies against Monkeypox virus in laboratory workers

Due to the discontinuation of routine smallpox vaccination after its eradication in 1980, a large part of the human population remains naïve against smallpox and other members of the orthopoxvirus genus. As a part of biosafety personnel protection programs, laboratory workers receive prophylactic vaccinations against diverse infectious agents, including smallpox. Here, we studied the levels of cross-protecting neutralizing antibodies as well as total IgG induced by either first- or third-generation smallpox vaccines against Monkeypox virus, using a clinical isolate from the 2022 outbreak. Serum neutralization tests indicated better overall neutralization capacity after vaccination with first-generation smallpox vaccines, compared to an attenuated third-generation vaccine. Results obtained from total IgG ELISA, however, did not show higher induction of orthopoxvirus-specific IgGs in first-generation vaccine recipients. Taken together, our results indicate a lower level of cross-protecting neutralizing antibodies against Monkeypox virus in recipients of third-generation smallpox vaccine compared to first-generation vaccine recipients, although total IgG levels were comparable.

Design and computational evaluation of a novel multi-epitope hybrid vaccine against monkeypox virus: Potential targets and immunogenicity assessment for pandemic preparedness

Monkeypox is a type of DNA-enveloped virus that belongs to the orthopoxvirus family, closely related to the smallpox virus. It can cause an infectious disease in humans known as monkeypox disease. Although there are multiple drugs and vaccines designed to combat orthopoxvirus infections, with a primary focus on smallpox, the recent spread of the monkeypox virus to over 50 countries have ignited a mounting global concern. This unchecked viral proliferation has raised apprehensions about the potential for a pandemic corresponding to the catastrophic impact of COVID-19. This investigation explored the structural proteins of monkeypox virus as potential candidates for designing a novel hybrid multi-epitope vaccine. The epitopes obtained from the selected proteins were screened to ensure their non-allergenicity, non-toxicity, and antigenicity to trigger T and B-cell responses. The interaction of the vaccine with toll-like receptor-3 (TLR-3) and major histocompatibility complexes (MHCs) was assessed using Cluspro 2.0. To establish the reliability of the docked complexes, a comprehensive evaluation was conducted using Immune and MD Simulations and Normal Mode Analysis. However, to validate the computational results of this study, additional in-vitro and in-vivo research is essential.

WITHDRAWN: Monkeypox: A Timely Update on the Global Outbreak, Transmission, Viral Replication, Vaccination and Clinical Strategies

Monkeypox virus is a zoonotic virus that can infect both humans and mammals. It is closely related to the smallpox virus. The first recorded human case of monkeypox (MPX) was documented in the Democratic Republic of the Congo in 1970. In April 2022, there was a significant surge in MPX cases across multiple African regions. This review provides an overview of the epidemiology, clinical presentation, genome structure, vaccination, diagnosis, public health strategies, and management of MPX. It emphasizes the importance of surveillance, vaccination, infection control, education, and supportive care. A coordinated, interdisciplinary approach involving public health authorities, healthcare professionals, and community engagement is essential for preventing and managing MPX outbreaks.

Hospitalization determinants in patients with Mpox disease: The CEME-22 Project

ObjectivesThis sub-analysis seeks to delineate and characterize factors influencing hospitalization in individuals diagnosed with Mpox disease amidst the initial outbreak in Spain in the onset of 2022. MethodsEmploying a non-probabilistic convenience sampling approach, a retrospective multicenter investigation was carried out to examine Monkeypox virus infection within Spanish healthcare facilities. ResultsThe median duration of the disease was 16 days, with 4.2 % of cases resulting in hospitalization. There was a single ICU admission leading to fatality. Sequelae were observed in 2.3 % of cases. Multivariate analysis revealed that hospitalization decisions were influenced by immunosuppression and severe symptoms, including gastrointestinal, neurological, ear-nose-throat, and respiratory manifestations. Significant analytical parameter differences were restricted to hemoglobin levels at diagnosis. ConclusionsThis study elucidates factors influencing hospitalization decisions for Monkeypox patients in Spain, emphasizing the importance of immunosuppression and extracutaneous symptoms involving the gastrointestinal, ear-nose-throat, and respiratory pathways. In summary, hospitalization determinations arise from the interplay of these crucial dimensions.

Haematological Profile of Patients Infected with Monkeypox Virus

The “Type of Article” of this paper is “Letter to the Editor”. This paper discuses about: “Haematological Profile of Patients Infected with Monkeypox Virus”. No formal abstract is available. Readers are requested to read the full article.

USAGE OF PARTICLE SWARM OPTIMIZATION IN DIGITAL IMAGES SELECTION FOR MONKEYPOX VIRUS PREDICTION AND DIAGNOSIS

Identifying skin diseases by using digital images of skin that are also automated, efficient, and accurate is critical for biomedical image analysis. Many researchers have developed numerous machine-learning techniques for the prediction and diagnosis of various diseases that help clinicians identify infections early and provide crucial data for virus management. In this work, we use the inherent attributes of Particle Swarm Optimization (PSO), such as exploration and exploitation, to identify images for monkeypox virus prediction and diagnosis. Alongside, monkeypox, chickenpox, smallpox, cowpox, measles, tomato flu, and normal skin images were all considered in this study for monkeypox virus prediction and diagnosis. We collect photos from the International Skin Imaging Collaboration (ISIC) for analysis and experimentation purposes. Finally, we compare the proposed model Particle Swarm Optimization- Monkeypox Virus (PSOMPX) for monkeypox virus identification with four distinct pre-trained deep learning models (e.g., VGG16, ResNet50, InceptionV3, and Ensemble). Then we use four performance evaluation metrics—accuracy, precision, recall, and F1 score—to evaluate the model and analyze the outcomes of experiments. The experimental results obtained through the PSOMPX model significantly outperform other models due to its numerous traits.

The Role of Tecovirimat in the Management of Monkeypox

Monkeypox is a self-limited disease with symptoms that disappear within 14 to 21 days. Clinical management of monkeypox includes general supportive care and the use of antivirals that have activity against the monkeypox virus. This literature study aims to describe the role of tecovirimat in the management of monkeypox. Tecovirimat is an antiviral drug approved by the U.S. Food and Drug Administration (FDA) as part of the treatment management of smallpox in adults and children. Evidence of the efficacy of tecovirimat as mpox therapy was obtained from animal studies, where tecovirimat reduced mortality rates, reduced duration of illness and viral shedding. Tecovirimat inhibits the vp37 viral protein encoded by the F13 gene of the variola virus. This protein is highly conserved in orthopoxviruses, allowing tecovirimat to have in vitro activity against several orthopoxviruses, including vaccinia, variola, cowpox, and monkeypox viruses. In conclusion, tecovirimat is used in monkeypox sufferers with severe clinical conditions (sepsis, encephalitis, extensive lesions, bleeding manifestations), patients at risk of experiencing severe clinical conditions (immunocompromised, pregnant or breastfeeding, history of psoriasis, varicella zoster infection) and patients with one or more complications.

A bioinformatics approach to systematically analyze the molecular patterns of monkeypox virus-host cell interactions

Monkeypox has been spreading worldwide since May 2022, when the World Health Organization (WHO) declared the outbreak a “public health emergency of international concern.” The spread of monkeypox has posed a serious threat to the health of people around the world, but few studies have been conducted, and the molecular mechanism of monkeypox after infection remains unclear. We therefore implemented a transcriptome analysis to identify signaling pathways and biomarkers in monkeypox-infected cells to help understand monkeypox-host cell interactions. In this study, datasets GSE36854 and GSE11234 were obtained from GEO. Of these, 84 significantly different genes were identified in the dataset GSE36854, followed by KEGG, GO analysis protein-protein interaction (PPI) construction, and Hub gene extraction. We also analyzed the expression regulation of hub genes and screened for drugs targeting hub genes. The results showed that monkeypox-infected cells significantly activated the cellular immune response. The top 10 hub genes are IER3, IFIT2, IL11, ZC3H12A, EREG, IER2, NFKBIE, FST, IFIT1 and AREG. AP-26113 and itraconazole can be used to counteract the inhibitory effect of monkeypox on IFIT1 and IFIT2 and serve as candidate drugs for the treatment of monkeypox virus infection. IRF1 may also be a transcription factor of IFIT. Our results provide a new entry point for understanding how monkeypox virus interacts with its host.

Monkeypox Virus Neutralizing Antibodies at Six Months from Mpox Infection: Virologic Factors Associated with Poor Immunologic Response.

A natural monkeypox virus infection may not induce sufficient neutralizing antibody responses in a subset of healthy individuals. The aim of this study was to evaluate monkeypox virus-neutralizing antibodies six months after infection and to assess the virological factors predictive of a poor immunological response. Antibodies were assessed using a plaque reduction neutralization test at six months from mpox infection; mpox cutaneous, oropharyngeal, and anal swabs, semen, and plasma samples were tested during infection. Overall, 95 people were included in the study; all developed detectable antibodies. People who were positive for the monkeypox virus for more days had higher levels of antibodies when considering all tested samples (p = 0.029) and all swabs (p = 0.005). Mpox cycle threshold values were not predictive of antibody titers. This study found that the overall days of monkeypox virus detection in the body, irrespective of the viral loads, were directly correlated with monkeypox virus neutralizing antibodies at six months after infection.

Circular RNA vaccines against monkeypox virus provide potent protection against vaccinia virus infection in mice

Since the outbreak of monkeypox (mpox) in 2022, widespread concern has been placed on imposing an urgent demand for specific vaccines that offer safer and more effective protection. Using an efficient and scalable circular RNA (circRNA) platform, we constructed four circRNA vaccines that could induce robust neutralizing antibodies as well as Tcell responses by expressing different surface proteins of mpox virus (MPXV), resulting in potent protection against vaccinia virus (VACV) in mice. Strikingly, the combination of the four circular RNA vaccines demonstrated the best protection against VACV challenge among all the tested vaccines. Our study provides a favorable approach for developing MPXV-specific vaccines by using a circular mRNA platform and opens up novel avenues for future vaccine research.

Nanopore adaptive sampling of a metagenomic sample derived from a human monkeypox case.

In 2022, a series of human monkeypox cases in multiple countries led to the largest and most widespread outbreak outside the known endemic areas. Setup of proper genomic surveillance is of utmost importance to control such outbreaks. To this end, we performed Nanopore (PromethION P24) and Illumina (NextSeq. 2000) Whole Genome Sequencing (WGS) of a monkeypox sample. Adaptive sampling was applied for in silico depletion of the human host genome, allowing for the enrichment of low abundance viral DNA without a priori knowledge of sample composition. Nanopore sequencing allowed for high viral genome coverage, tracking of sample composition during sequencing, strain determination, and preliminary assessment of mutational pattern. In addition to that, only Nanopore data allowed us to resolve the entire monkeypox virus genome, with respect to two structural variants belonging to the genes OPG015 and OPG208. These SVs in important host range genes seem stable throughout the outbreak and are frequently misassembled and/or misannotated due to the prevalence of short read sequencing or short read first assembly. Ideally, standalone standard Illumina sequencing should not be used for Monkeypox WGS and de novo assembly, since it will obfuscate the structure of the genome, which has an impact on the quality and completeness of the genomes deposited in public databases and thus possibly on the ability to evaluate the complete genetic reason for the host range change of monkeypox in the current pandemic.

Repositioning of anti-infective compounds against monkeypox virus core cysteine proteinase: a molecular dynamics study.

Monkeypox virus (MPXV) core cysteine proteinase (CCP) is one of the major drug targets used to examine the inhibitory action of chemical moieties. In this study, anin silico technique was applied to screen 1395 anti-infective compounds to find out the potential molecules against the MPXV-CCP. The top five hits were selected afterscreening and processed for exhaustive docking based on the docked score of ≤ -9.5kcal/mol. Later, the top three hits based on the exhaustive-docking score and interaction profile were selected to perform MD simulations. The overall RMSD suggested that two compounds, SC75741and ammonium glycyrrhizinate, showed a highly stable complex with a standard deviation of 0.18 and 0.23nm, respectively. Later, the MM/GBSA binding free energies of complexes showed significant binding strength with ΔGTOTALfrom -21.59 to -15kcal/mol.This report reported the potential inhibitory activity of SC75741 and ammonium glycyrrhizinate against MPXV-CCP by competitively inhibiting the binding of the native substrate.

Molecular Docking of Seaweed-Derived Drug Fucoxanthin Against the Monkeypox Virus.

Background The monkeypox virus (MPXV) is classified as a zoonotic virus of the Poxviridae family, resulting from the MPXV strain of the Orthopoxvirus genus. Seaweeds, or marine macroalgae, are abundant reservoirs of bioactive compounds that demonstrate diverse biological properties, such as antiviral actions. In the field of computational analysis, in silico analysis refers to the use of computer-based methods to study and assess biological systems and processes. To forecast the binding affinity and interaction between the discovered chemical and the target proteins of the MPXV, a molecular docking analysis was conducted. Aim The research aims to conduct an in silico examination of a protein-ligand interaction of a drug produced from seaweed that targets the MPXV. Methodology Protein Data Bank (PDB) and PubChem databases provided MPXV methyltransferase and fucoxanthin ligand compounds. AutoDockTools 1.5.7 calculated the molecular docking using the Lamarckian genetic algorithm. Autogrid created a grid box around target 8B07 active site hotspot residues. Each docked molecule's docking parameters were obtained from 100 docking experiments with a maximum of 2.5 × 106 energy evaluations, a 0.02 mutation rate, and a 0.8 crossover rate. The population comprised 250 randomly selected volunteers. PyMOL was utilized to observe ligand fragment interactions. Results The binding energy of the ligand fucoxanthin was -5.46 kcal/mol. Fucoxanthin interacts with receptor molecules via hydrogen bonding at the amino acid level: Chain A: PHE188 and TYR189; and Chain B: LYS33, GLN37, GLY38, GLY96, ARG97, PHE115, PRO202, and SER203. The higher the negative docking score, the stronger the binding affinity between the receptor and ligand molecules, indicating that bioactive substances are more effective. Conclusion The findings of this study indicate that fucoxanthin, a pharmaceutical derivative generated from seaweed, had antiviral activity against the MPXV. This conclusion was reached based on protein-ligand interactions.