Search Results (354)

Monkeypox virus (MPXV) is emerging as a global public health concern due to its nature of spread. There are limited treatment options, as the sole drug for treatment is lacking, highlighting the need for new therapeutic options. The use of computer-aided drugs discovery such as molecular docking, molecular dynamic (MD) simulations and post-simulation analysis are important tools in identifying potential compounds that can target specific proteins of the virus, such as DNA polymerase to stop virus replication. This study employed molecular docking and molecular simulation with the aim to identify potential inhibitors for MPXV treatment from the ZINC Database. Molecular docking was performed using PyRx 0.8 version after virtual screening of the ZINC database using the Tranches tool; then, toxicity prediction of the selected compounds was performed using the ProTox-3.0 web server. Molecular dynamics simulation was conducted using GROMACS version 4.5 to evaluate the structural stability and dynamic behavior of the protein–ligand complex for the best interacting compound. Furthermore, post-simulation analysis was conducted using standard GROMACS utilities for visualizing time-dependent properties from MD simulations. A total of 16 compounds were shortlisted based on their molecular docking scores and interaction profiles with the monkeypox virus DNA polymerase (PDB ID: 8HG1). The leading compound, ZINC000019418450, demonstrated strong binding affinity (−7.4 kcal/mol). According to post-simulation analysis, all top compounds formed between one and five hydrogen bonds and up to eleven hydrophobic contacts with residues within the active site, thus providing strong geometric and energetic evidence for binding stability. Notably, our identification of ZINC000104288636 as a Class 6 compound with an LD₅₀ of 23,000 mg/kg adds translational value by highlighting candidates with low predicted acute toxicity. Overall, this study lays a solid foundation for the rational design of next-generation monkeypox antiviral therapeutics. Future work is needed for experimental validation of prioritized compounds to assess their biochemical efficacy and pharmacological potential. Full article

Monkeypox virus, a zoonotic DNA virus belonging to the Orthopoxvirus genus, has emerged as a global health issue because of its fast spread to 104 nations over six continents. In the current study, an immunoinformatics pipeline was used to design a multiepitope-based prophylactic vaccine targeting the A35R glycoprotein and E8L membrane proteins of the monkeypox virus. Selected target proteins were surface-exposed, non-homologous to the human proteome, and essential for viral pathogenesis. B-cell and T-cell (MHC-I and MHC-II) epitopes with high antigenicity (>0.5), non-allergenicity, non-toxicity, and highly soluble in water with strong affinity towards innate and adaptive receptors, were prioritized. Shortlisted epitopes were combined to design the final vaccine utilizing an adjuvant (50S ribosomal L7/L12) and appropriate linkers for improved immunogenicity. Population coverage analysis showed wide HLA representation with 83.57% (MHC-I) and 88.8% (MHC-II) global coverage, including 89.6% for West Africa and 87.3% for Central Africa. Docking analysis of the vaccine construct with the TLR-4 receptor revealed stable interactions (−695.6 kcal/mol). Molecular dynamics simulations and binding free energies further confirmed structural stability. Immune simulations predicted strong activation of both humoral and cellular immune responses. These results indicate that the designed multiepitope vaccine construct is a viable option for additional experimental validation against the monkeypox virus. Full article

Monkeypox (Mpox) disease, caused by the Monkeypox virus (Mpox virus), emerged as a significant global health threat during the 2022 outbreak, prompting the World Health Organisation (WHO) to declare it a Public Health Emergency of International Concern (PHEIC). Rapid evolution through genomic modifications enhanced its outbreak potential. Zoonotic transmission occurs through close contact with infected rodents or primates; human-to-human transmission occurs via close contact or homosexual intercourse. The virus disseminates via the lymphatic system, causing symptoms ranging from mild skin lesions to severe multi-system complications or even death. Diagnosis incorporates clinical symptoms as well as advanced molecular and immunological methods. Currently, no specific antiviral medications or vaccines are available for Mpox, necessitating reliance on conventional therapeutic supports and treatments developed for smallpox. Raising awareness, promoting protective practices, implementing surveillance, enabling rapid diagnosis, ensuring timely treatment, and promoting mass vaccination are crucial to curb Mpox transmission. This narrative review provides a comprehensive overview of the current knowledge on epidemiology, evolution, transmission, pathogenesis, clinical signs, diagnosis, treatment, vaccination, and prevention strategies for Mpox. Full article

Background: The global spread of monkeypox virus (MPXV) highlights an urgent need for thermostable and easily administrable vaccines. Current orthopoxvirus vaccines are limited by cold-chain dependence and inconvenient injection-based delivery. Objectives: This study aimed to develop a dissolvable microneedle (DMN) vaccine against monkeypox based on a replication-deficient orthopoxvirus platform, through systematic formulation screening, stabilization mechanism exploration, and rigorous in vivo immunogenicity evaluation. Methods: A film-based approach was adopted for efficient, high-throughput formulation screening and thermostability assessment. NTV was mixed with excipients and dried into solid films. Stability was monitored via RT-qPCR after storage at 4 °C to 40 °C. The lead formulation was physically characterized, then used to fabricate MVA-BN-loaded DMN patches, which were further evaluated for in vivo immunogenicity via immunization in BALB/c mice. Results: The optimal formulation F2 (containing dextran, L-threonine, and BSA/HSA) showed a potency loss of only ~1 log₁₀ after 2 months at 25 °C, and <1 log₁₀ loss after 1 week at 37 °C. SEM revealed a porous virus-entrapment morphology, and FTIR indicated enhanced hydrogen bonding between the virus and the dextran matrix. The formulation was successfully manufactured into DMNs that dissolved within 5 min. In mice, these DMNs elicited robust MPXV-specific IgG and neutralizing antibody responses, with immunogenicity comparable to that induced by conventional intramuscular injection. Conclusions: This study successfully established a thermostable formulation and dissolvable microneedle delivery platform for replication-deficient orthopoxvirus vaccines against monkeypox. The optimized DMN vaccine induced robust MPXV-specific immune responses in mice with immunogenicity comparable to intramuscular injection, addressing the core limitations of current vaccines and providing a promising solution for monkeypox prevention. Full article

Mpox is a zoonosis caused by the monkeypox virus. Here, we report Mali’s index Mpox case, which was clinically identified at the Mali–Guinea border by the national telemedicine center and confirmed by PCR. The library prepared with NextGenPCR™ MPXV Sequencing Library Prep and sequenced on Minion MK1C revealed a genome length of 197,122 bp with an average depth of 1284.4×. The strain belonged to Clade IIb G1 lineage and exhibited 85 mutations relative to NC_063383.1. To decipher genomic epidemiology, genomes ≥ 195 kb were retrieved from NCBI and aligned with MAFFT. Time-resolved phylogenetic reconstruction and ancestral trait inference were performed with TreeTime v0.11.4. A median joining network was built with Popart v1.7. Phylogeographic analysis revealed clustering with Clade IIb (G.1 lineage) linked to the May 2025 outbreak in Sierra Leone. Full article

Since 2022, global outbreaks of monkeypox virus (MPXV) have been repeatedly designated by the World Health Organization (WHO) as a public health emergency of international concern (PHEIC), underscoring the urgent need to elucidate the multidimensional mechanisms underlying viral evolution and transmission. Current understanding remains largely focused on genomic variation, while the critical role of epigenetic regulation has been considerably overlooked. To address this gap, this study integrates high-throughput evolutionary genomic analysis with whole-genome DNA methylation profiling. Using parallel Illumina and Nanopore sequencing platforms, we comprehensively characterized two clinically derived MPXV isolates collected locally. The results revealed that both isolates belonged to the C.1.1 ancestral lineage, diverging into distinct clades (E.3 and E.4, respectively, supporting the presence of at least two independent viral introduction events into the region, each followed by limited local transmission. They had accrued a considerable number of single-nucleotide polymorphisms (SNPs), with APOBEC3-associated substitutions constituting 84.8% and 77.6% of all observed mutations. Furthermore, both 5-hydroxymethylcytosine (5hmC) and N6-methyladenine (6mA) modifications were identified and found to be preferentially enriched within the inverted terminal repeats (ITRs) regions of MPXV genome in both viral strains; moreover, the E.4 lineage viral strain exhibits a markedly more intricate and compositionally diversified modification landscape, a pattern that indicates appreciable epigenetic heterogeneity among MPXV lineages. Our study furnishes a multi-omics framework that presents a systematic evolutionary feature of two clinical MPXV isolates and their genomic DNA 5hmC and 6mA modification topologies, and enhances our understanding of MPXV viral adaptation and diversification. Full article

The 2022 global mpox outbreak represented a turning point in the Monkeypox virus (MPXV) epidemiology, highlighting the incredible capability of this virus to adapt to different conditions, also in a non-endemic context. To investigate the genomic dynamics of MPXV 2022 strains, we performed whole-genome sequencing of 40 clinical samples from 16 Italian patients across multiple anatomical sites and timepoints between May and December 2022. Combining single-nucleotide analysis with detailed investigation of short tandem repeats (STRs), we explored inter- and intra-host viral dynamics. We identified 19 STR loci located near or within genes involved in immune modulation and virion morphogenesis. While most STRs remained stable across patients, a subset displayed locus- or matrix-specific variation. Among these, STR-VII—embedded within the coding sequence of OPG153, an envelope-associated protein implicated in viral attachment—showed a 12-nucleotide in-frame deletion, resulting in the loss of four aspartic acid residues (Δ4D variant). Structural modeling indicated that this deletion slightly alters a disordered acidic loop without affecting the global fold, potentially modulating surface charge and immune recognition. Integrating STR profiling into genomic surveillance may enhance resolution in outbreak reconstruction and reveal subtle adaptive processes underlying poxvirus–host interaction and immune escape. Full article

Monkeypox (Mpox), a zoonotic viral disease caused by the Monkeypox Virus (MPXV), has gained significant attention in recent years due to its increasing incidence and the grave threat it poses to global health. MPXV has spread at a rapid pace during the COVID-19 pandemic, causing 10,000+ confirmed cases and ~300 fatalities in 122 countries. This virus comprises two major clades, Clade I (Central African), which is evidently more virulent, and Clade II (West African), which has caused the recent outbreaks across the world and caused fewer deaths. Clinically, Mpox presents as a milder form with fever, lymphadenopathy, and vesiculopustular rash similar to smallpox. Diagnostic measures such as polymerase chain reaction (PCR) are the main diagnostic confirmatory tools. Advanced diagnostics involve electronic microscopy, serology, and immunohistochemistry. Alternative drugs like tecovirimat and brincidofovir have demonstrated potential for treating smallpox, but there is scanty evidence on their efficacy against MPXV. Most recent advancements in the study of vaccines have resulted in the creation and introduction of MVA-BN (JYNNEOS/Imvanex/Imvamune) and ACAM2000 vaccines, which conferred cross-protection against MPXV. MVA-BN is suggested to perform better than other types due to its enhanced safety and immunogenicity. Researchers are also developing DNA and protein subunit vaccines against Mpox to induce specific immune responses by presenting viral proteins. The discovery of novel vaccine candidates and antiviral treatments will be needed to prevent future outbreaks and reduce the global health burden of Mpox. This review focuses on the characterization of MPXV, summarizing current knowledge on its genomic structure, pathogenesis, replication, potential targets of anti-MPXV drugs, clinical features, and epidemiological patterns, along with recent advances in vaccine development. Full article

Monkeypox virus (MPXV) is a zoonotic Orthopoxvirus responsible for Monkeypox (Mpox), historically associated with sporadic zoonotic transmission but increasingly characterised by sustained human-to-human spread. While vaccinia-based vaccination is known to confer cross-protection against MPXV, the durability of such immunity over a human lifetime remains incompletely characterised. Here, we assessed humoral and cellular immune responses to MPXV in octogenarians and nonagenarians vaccinated against smallpox during childhood. Twenty-three adults aged 79–94 years (median 83), who self-reported childhood vaccinia vaccination between 1925 and 1940, were recruited. MPXV-specific antibody responses were evaluated using ELISA, targeting homologous vaccinia and MPXV proteins, and live-virus neutralisation assays. Cellular immunity was assessed by IFN-γ ELISpot following stimulation with peptide pools derived from highly conserved vaccinia antigens. Responses were also obtained from younger, recently MVA–BN-vaccinated and unvaccinated control donors. All historically vaccinated participants exhibited MPXV-reactive IgG responses, with antibody binding and neutralisation levels comparable to recently vaccinated individuals. Functional neutralising activity against MPXV was detected in all donors, with ≥50% neutralisation observed in 78% of participants. Antibody concentrations correlated strongly with neutralisation capacity. T-cell responses were detectable in all historically vaccinated donors, most prominently against the major core protein A10L, although reduced magnitudes were observed in participants over 90 years of age. No MPXV-specific humoral or cellular responses were detected in unvaccinated controls. These findings demonstrate that childhood vaccinia vaccination induces durable humoral and cellular immunity against MPXV persisting for over seven decades. Historical smallpox vaccination status may therefore remain a relevant determinant of protection against Mpox. Full article

Mpox is an emerging zoonotic infection caused by the Monkeypox virus, an Orthopoxvirus with increasing global relevance following the 2022 multinational outbreak. Historically endemic to Central and West Africa, the disease has evolved from sporadic zoonotic transmission to sustained human-to-human spread, particularly through close physical and intimate contact. Clinical manifestations typically include fever, lymphadenopathy, and progressive mucocutaneous lesions, although severity varies according to viral clade, immune status, and comorbidities. The 2022 outbreak, predominantly associated with the Clade IIb variant, was characterized by milder disease, localized lesions, and reduced mortality compared with the more virulent Clade I variant. Despite this, severe outcomes remain possible, particularly in vulnerable groups such as children, pregnant individuals, immunocompromised patients, and persons with extensive dermatological disorders. Diagnosis relies primarily on polymerase chain reaction testing from lesion-derived samples, with genomic sequencing serving as a complementary tool for epidemiological surveillance. Management is largely supportive, though antivirals such as tecovirimat may be considered in severe cases or in high-risk populations. Data regarding therapeutic safety in pregnancy are limited; however, tecovirimat appears to have the most favorable profile, whereas cidofovir and brincidofovir remain contraindicated. Prevention strategies include targeted vaccination with the non-replicating Modified Vaccinia Ankara–Bavarian Nordic vaccine, used for both pre- and post-exposure prophylaxis, particularly in individuals at elevated risk. Given the evolving epidemiological profile, the potential for vertical transmission, and the risk of adverse perinatal outcomes, Mpox infection during pregnancy poses unique clinical challenges. This review synthesizes current evidence on virology, clinical presentation, diagnosis, prevention, and management, with an emphasis on obstetric considerations and public health implications. Full article

Introduction: Despite the impressive progress carried out in the field of biomedical sciences in recent decades, the incidence of emerging and neglected lethal viral infections mainly belonging to the Coronaviridae, Filoviridae, Arenaviridae, Bunyaviridae, and Paramyxoviridae families has considerably impaired human health. The worldwide vaccination campaign at the end of the 1970s determined the eradication of smallpox. However, the growing number of cases of diseases linked to orthopoxvirus diseases, such as the recent epidemic of monkeypox zoonosis in various countries around the world, has increased the need for knowledge of these viral pathogens. To date, there is no specific treatement for Monkeypox virus (MPXV) infection. However, several antiviral drugs used to treat Smallpox and other viral infections could also be beneficial for Monkeypox disease. In this study we report the design and synthesis of new, variously substituted benzimidazole derivatives and the evaluation of their cytotoxicity and antiviral activity against representatives of the Orthopoxvirus genus, Vaccinia Virus (VV), closely related to variola virus and MPXV. Methods: A combination of cell-based assays and experimental techniques was used to investigate the cytotoxicity, antiviral activity, and mechanisms of action of the most interesting compound. Results: In our study, new, variously substituted benzimidazoles showed interesting EC₅₀ values against vaccinia and MPXV and a cytotoxic profile in the high micromolar range. Conclusions: Our work shows that the new tested benzimidazole derivatives possess appealing activity and selectivity, accompanied by low cytotoxicity. These results set a valid foundation with which to identify potent and selective anti-Poxvirus agents. Full article

Monkeypox (MPOX) is an emerging zoonotic disease caused by monkeypox virus (MPXV), an orthopoxvirus closely related to smallpox. Initially confined to endemic regions in Central and West Africa, MPOX has recently gained global significance with outbreaks reported across multiple continents. MPXV is maintained in animal reservoirs but is increasingly transmitted from person to person, facilitated by close contact, respiratory droplets, and, in some cases, sexual transmission. Clinically, MPOX presents with fever, lymphadenopathy, and a characteristic vesiculopustular rash, though atypical manifestations have been observed in recent outbreaks, complicating diagnosis. Laboratory confirmation relies on molecular testing, while differential diagnosis must consider varicella, herpes, and other vesicular illnesses. Therapeutic options remain limited; supportive care is the cornerstone of management, but antivirals such as tecovirimat and brincidofovir, as well as smallpox vaccines, have shown efficacy in mitigating disease severity and preventing infection. The unprecedented global outbreak has underscored the importance of surveillance, rapid diagnostics, and coordinated public health responses to contain transmission. This review provides an overview of epidemiology, virology, clinical manifestations, modes of transmission, available diagnostics, and prophylactic and therapeutic strategies against MPOX. We also discuss the role of animal reservoirs, viral evolution, and human-to-human transmission in shaping the dynamics of recent MPOX outbreaks. By summarizing the latest evidence, this review aims to inform clinicians, researchers, and policymakers about key aspects of MPOX biology, clinical management, and prevention, while identifying gaps that warrant future investigation for the control of this and potentially other emerging zoonotic-related pathogens with an impact on human health. Full article

The monkeypox virus (MPXV) is an emerging zoonotic pathogen responsible for mpox, a disease characterized by some smallpox-like symptoms, typically mild but occasionally fatal. The largest mpox recorded global outbreak began in May 2022, with over 162,000 cases across 140 countries. Herein, we have analyzed the intra-clonal diversity of MPXV obtained from a single skin lesion sample from a male patient (June 2022). Three viral clones were obtained following phenotypic evaluation of MPXV lysis plaque characteristics over a three-course infection in BSC-40 cells. Unlike the vaccinia virus Western Reserve (VACV-WR) strain, MPXV clones did not produce comet-like structures, suggesting reduced extracellular enveloped virus (EEV) morphotype release, which is associated with viral dissemination. Whole-genome sequencing and assembly identified subtle differences among clones. Comparative genomic analyses, including synteny and single nucleotide variation (SNV) calling, revealed intra-clonal differences and divergence from clade I and II references, although the variety of mutations found did not reveal possible variations at the protein level. Altogether, these findings suggest that although similar, it is possible that distinct MPXV variants may circulate together and can be found in a single exanthematous lesion. Full article

Background: Human monkeypox is a zoonotic disease caused by the monkeypox virus (MPXV), endemic in Central and West Africa. A significant 2022 outbreak affected 104 countries, driven by increased susceptibility due to the cessation of smallpox vaccination, global travel, and interactions with infected animals. Strengthening surveillance, public health measures, and raising awareness are essential for early diagnosis, vaccination acceptance, and preventing future outbreaks. Methods: The survey was distributed to 645 nursing students of the University of Palermo between July 2022 and August 2022, and we estimated the knowledge, attitudes and behaviors through a KAP Survey. Descriptive statistics were used to summarize the data, while chi-squared, Fisher’s exact, and Student’s t-tests were employed to analyze differences between groups, with statistical significance set at p < 0.05. At least 80% of the students surveyed had already taken the microbiology exam, as microbiology is studied in the first year of the Bachelor of Science in Nursing program at the University of Palermo. Results: The survey showed a predominantly young, female nursing student population with limited knowledge of monkeypox, as only 3.88% demonstrated adequate understanding. Despite this, attitudes toward prevention were positive, with 82.64% scoring adequately and 41.09% expressing strong willingness to get vaccinated. Knowledge improved with academic progression (p = 0.005), while attitudes and behaviors remained consistent. These findings imply a critical gap in education; the limited knowledge, especially regarding transmission and severity, may lead to an underestimation of the risks associated with global infectious diseases. This underscores the need to better prepare future healthcare professionals for public health emergencies Conclusions: The study found that nursing students had limited knowledge of monkeypox, especially regarding epidemiology and disease severity. Despite positive attitudes toward vaccination, some behaviors reflected an underestimation of global infection risks. Knowledge improved with academic progression, underscoring the importance of education. Targeted educational programs are needed to enhance awareness and preparedness for future outbreaks. Full article

The ongoing global monkeypox outbreak since 2022 has highlighted the urgent need for vaccine development. Current vaccination strategies rely on cross-protective immunity provided by orthopoxvirus-based live-attenuated vaccines. However, these vaccines not only exhibit suboptimal efficacy against monkeypox virus (MPXV) but also raise safety concerns, particularly given the significant global overlap between MPXV infections and HIV. Owing to their superior safety profile and accessibility, recombinant subunit vaccines represent a highly promising platform for monkeypox vaccine development. In this study, we developed a subunit vaccine comprising A29L, B6R, and M1R antigens formulated with a proprietary nanoemulsion adjuvant and evaluated its immunogenicity and protective efficacy. In mice immunized with a prime-boost regimen of the three individual antigens combined with the nanoemulsion adjuvant, comparable serum IgG levels against each antigen were elicited. Both A29 and M1 formulations induced serum antibodies with potent neutralizing activity against MPXV and Vaccinia virus Western Reserve strain (VACV-WR). Notably, M1 antiserum exhibited stronger neutralization than A29 antiserum, whereas B6R immune serum showed no significant neutralizing activity. Splenocytes from B6R-immunized mice mounted a robust IFN-γ response, which was markedly lower in those immunized with A29 or M1. All three monovalent vaccines conferred complete survival following an intranasal lethal MPXV challenge, with M1 providing the strongest protection. In a lethal VACV-WR challenge model, only M1 immunization conferred significant protection. Histopathological analysis of lung tissues on day 5 post-infection revealed more pronounced inflammatory features in B6R-immunized mice compared to the nanoemulsion adjuvant control group. Furthermore, the nanoemulsion-adjuvanted bivalent A29L + B6R formulation induced significantly higher IgG and neutralizing antibody titers and demonstrated superior protective efficacy compared to the aluminum hydroxide-adjuvanted formulation. This comparative preclinical evaluation provides important evidence to support the development of a safe and effective subunit vaccine against monkeypox. Full article