Search Results (43)

Oropouche virus (OROV), an emerging orthobunyavirus of increasing public health concern in the Americas, currently lacks approved antiviral therapies. In this study, we employed a structure-based in silico approach to identify natural antiviral scaffolds capable of targeting the Gc glycoprotein, a class II fusion protein essential for host membrane fusion and viral entry. A library of 537 plant-derived compounds was screened against the Gc head domain (PDB ID: 6H3X) through molecular docking and redocking, followed by 100-nanosecond molecular dynamics simulations, MM-PBSA free energy calculations, and ADMET profiling. Curcumin and Berberine emerged as standout candidates. Curcumin demonstrated a balanced profile, with stable binding (−38.14 kcal/mol), low backbone RMSD (1.82 Å), and consistent radius of gyration (Rg ~ 18.8 Å), suggesting strong conformational stability and compactness of the protein–ligand complex. Berberine exhibited the most favorable binding energy (−13.10 kcal/mol) and retained dynamic stability (RMSD 1.86 Å; Rg ~ 19.0 Å), though accompanied by predicted cytotoxicity that may require structural refinement. Both compounds induced reduced residue-level fluctuations (RMSF < 2.5 Å) in functionally critical regions of the Gc protein, consistent with a mechanism of action that involves stabilization of the prefusion conformation and interference with the structural transitions required for viral entry. These findings identify curcumin and berberine as promising scaffolds for anti-OROV drug development and offer a rational foundation for future experimental validation targeting viral fusion mechanisms. Full article

Oropouche virus (OROV) is an emerging arbovirus responsible for Oropouche fever, also known as sloth fever, a febrile illness that can lead to recurrent outbreaks in affected regions. Endemic to parts of South and Central America, OROV is primarily transmitted by biting midges (Culicoides paraensis), although mounting evidence implicates mosquitoes, particularly the Culex and Aedes species, as additional vectors. Recent ecological disturbances—such as deforestation, urbanization, and climate change—have driven significant shifts in vector population dynamics, contributing to the expanded geographic range and increased transmission of OROV. Notably, recent reports of OROV infections among American and European travelers to Cuba highlight the virus’s growing potential for international dissemination and underscore its significance as a global health concern. OROV is an enveloped orthobunyavirus within the Peribunyaviridae family, possessing a tripartite, single-stranded, negative-sense RNA genome composed of the S (small), M (medium), and L (large) segments. These segments encode the nucleocapsid (N) protein, glycoproteins (Gn and Gc), and RNA-dependent RNA polymerase, respectively. Despite increasing incidence and potential for global spread, no licensed vaccines or antiviral therapies currently exist, and effective diagnostic tools remain limited. Furthermore, although human-to-human transmission has not been observed, the absence of robust surveillance systems complicates timely outbreak detection and response. In this study, we present a comprehensive molecular characterization of OROV’s major structural proteins, with an emphasis on structural modeling and epitope prediction. By integrating bioinformatics approaches with available structural data, we identify key antigenic regions that could serve as targets for the development of serological diagnostics and vaccine candidates. Our findings contribute critical insights into the molecular virology of OROV and provide a foundational framework for future efforts aimed at the prevention, diagnosis, and control of this neglected tropical pathogen. These advancements are essential for mitigating the impact of OROV in endemic regions and reducing the risk of global emergence. Full article

Oropouche virus (OROV), an emerging arbovirus of the Peribunyaviridae family, is responsible for acute febrile illness and, in some cases, neurological or hemorrhagic complications. Although traditionally confined to tropical areas of Central and South America, the 2024–2025 epidemic has signaled a major shift in its geographic and clinical profile, with sustained transmission in the Caribbean, over 15,000 confirmed cases, and the first imported infections reported in Europe and the United States. New clinical observations include fatalities in previously healthy adults, suspected vertical transmission with adverse fetal outcomes, and potential sexual transmission. Despite entomological data indicating low competence of European mosquito species and the absence of the main vector Culicoides paraensis, the increasing frequency of imported cases underscores the need for continued vigilance. Diagnostic limitations and clinical overlap with other arboviruses further complicate early detection. This review summarizes current knowledge on OROV’s epidemiology, transmission dynamics, and clinical features, and highlights the urgent need for integrated surveillance, diagnostic readiness, and coordinated research efforts. Emphasis is placed on Europe’s preparedness strategies, with Italy’s Jubilee 2025 offering a real-world case study for managing arboviral threats during mass gatherings. Full article

The Orthobunyavirus Oropouche (OROV) has become an urgent public health threat in Central and South America, as well as in other countries worldwide. Since its initial identification, there have been over 30 outbreaks, with the largest reported in late 2024 in Brazil. This outbreak prompted an epidemiological alert due to a significant increase in OF cases in non-Amazonian states in the Americas region, as well as in European countries, where 44 imported cases were identified. Humans become infected predominantly through the bite of the Culicoides paraensis midge, and the symptoms could be misinterpreted due to their similarity to those of other arboviral infections. Due to the lack of a point-of-care test, RT-qPCR is currently the key diagnostic test during the acute phase of the disease. This review focuses primarily on the available molecular and serological diagnostic methods. The latter could indeed be used as a confirmation test to monitor the patient’s immunological status and better distinguish between cross-reacting arboviruses. In addition, this review explains also the existing sequencing methods required to enforce the surveillance system for OROV reassortant species that could cause a new worldwide outbreak. The information gathered could provide a valuable basis for implementing additional surveillance systems in those countries lacking up-to-date data. Full article

The simultaneous circulation of multiple arboviruses, often driven by (re)emergence events, poses challenges to public health systems. In Brazil, the co-circulation of Dengue virus (DENV), Zika virus (ZIKV), Chikungunya virus (CHIKV), and Oropouche virus (OROV), together with the potential urban emergence of Mayaro virus (MAYV), underscores the importance of understanding interactions among these pathogens within their vectors. This study investigated the effects of CHIKV and MAYV coinfection and superinfection on replication dynamics in Aedes aegypti. Mosquitoes were experimentally exposed to CHIKV and MAYV through artificial blood meals under coinfection and superinfection conditions. Infection (IR), dissemination (DR), and transmission (TR) rates, as well as viral loads, were quantified by quantitative reverse transcription PCR (qRT-PCR). To confirm viral replication and assess cytopathic effects, positive saliva samples were inoculated in Vero cells, followed by serial passages and plaque assays for viral titration. The results showed that Ae. aegypti is capable of transmitting both CHIKV and MAYV concurrently during coinfection. However, in superinfection scenarios, prior infection with either virus significantly reduced the transmission efficiency of the subsequently acquired virus, indicating viral interference at the replication level. These findings underscore the complexity of arboviral interactions within vectors and highlight their potential implications for transmission dynamics. Continuous entomo-virological surveillance and targeted research are essential for anticipating and mitigating the impact of arboviral co-circulation in endemic regions. Full article

Background/Objective: Oropouche virus (OROV—Orthobunyvirus oropoucheense) is a neglected arbovirus endemic to parts of Latin America, particularly the Brazilian Amazon. Despite its increasing epidemiological relevance, little is known about healthcare professionals’ awareness and preparedness regarding the virus. Methods: A cross-sectional, questionnaire-based study was conducted between February 2024 and March 2025 with 760 healthcare professionals across 21 Brazilian states. Participants represented various professional categories, including nursing, medicine, pharmacy, and biomedical sciences. The survey assessed knowledge on OROV epidemiology, clinical recognition, diagnostic practices, and compulsory notification. Results: Among participants, 37.4% had never heard of OROV, and 38.0% had heard of it but knew little about it. Most professionals first learned about the virus within the past year (31.8%). The majority (86.1%) reported not having received information about OROV during undergraduate education. Only 21.9% knew which diagnostic test to request, and 64.7% were aware that OROV is subject to mandatory notification. Notably, 71.2% were unaware of the virus’s potential neurological complications. Conclusions: These findings reveal a significant gap in the education and training of healthcare professionals regarding OROV, even in endemic areas. The results underscore the need for curricular reform, expanded continuing education, and stronger integration of OROV into national epidemiological surveillance efforts. Full article

The Oropouche virus (OROV) has been circulating in the Amazon region since the 1960s, with a progressive increase in outbreaks and human cases reported in Brazil and neighboring countries. In the Rio de Janeiro state, there has been a significant rise in suspected cases of arboviruses, with only 30% of laboratory tests confirming infections with dengue, Zika, or chikungunya viruses. The investigation of OROV virus circulation in the Rio de Janeiro state was initiated and confirmed in April 2024. Our study aimed to retrospectively investigate OROV infections in dengue-suspected cases with inconclusive diagnosis in order to better understand the temporal and geographic introduction of OROV in the Rio de Janeiro state. Municipalities from Rio de Janeiro with arbovirus-like fever cases but a low percentage of dengue-positive RT-PCR test confirmations were identified in the laboratory database. Samples were selected for testing OROV infections using real-time RT-PCR as recommended by the Brazilian Ministry of Health. Municipalities in the Middle Paraíba region of the state showed 93% negative tests results for dengue, Zika, and chikungunya starting in September 2023. A total of 118 positive cases of Oropouche were recorded in the state of Rio de Janeiro between March and July 2024. Moreover, by genome sequencing of eight strains, it was shown that OROV circulating in Rio de Janeiro belongs to recently emergent M₁L₂S₂ lineage. Our findings retrospectively revealed a concentration of cases in the Middle Paraíba region and an outbreak in the rural village of Cacaria, located in the municipality of Piraí. According to our data, this region is the first area with sustained transmission in the Rio de Janeiro state. Full article

Background/Objectives: This study aimed to examine the effects of a Fucoidan-rich extract from Saccharina latissima (SLE-F) on differential gut microbiota composition, intestinal inflammation status, and microbial functional gene expression in participants infected with Dengue or Oropouche virus at the Hermanos Ameijeiras Hospital in Havana, Cuba. Methods: Fecal samples were collected at baseline, day 28, and day 90 from 90 healthy adults, some of whom contracted the virus during the study period. Functional gene analysis was conducted using two approaches—the Kruskal–Wallis H test and linear discriminant analysis effect size—applied to ortholog-level data normalized by read count and gene copy number. Results: Infected participants exhibited significantly lower Lachnospiraceae-to-Enterobacteriaceae (LE) ratios, indicating increased intestinal inflammation. High-dose SLE-F treatment led to a significant reduction in the LE ratio (p = 0.006), suggesting a strong anti-inflammatory effect. Microbiome analysis revealed a shift from dysbiosis to a more balanced composition by the end of the study, characterized by increased abundances of Akkermansia muciniphila, Bifidobacterium adolescentis, and B. longum, along with decreased pro-inflammatory taxa such as Fusobacterium. Conclusions: Genetic analysis provided distinct yet complementary insights into the microbiome’s functional responses to infection and therapeutic modulation by Fucoidan. These findings highlight the therapeutic potential of high-dose Fucoidan in reducing gut inflammation and promoting microbiome recovery following viral infections. Full article

Mosquitoes of the Aedes and Culex genera are primary vectors of arboviruses such as the dengue, Zika, chikungunya (CHIKV), Oropouche, and West Nile viruses, causing millions of infections annually. Standard virus detection in mosquitoes requires capturing, transporting, and processing samples with a cold chain to preserve RNA, which is challenging in resource-limited areas. FTA cards preserve viral RNA at room temperature and have been used to collect mosquito saliva, a key sample for assessing transmission. However, most FTA-based traps require electricity or CO₂, limiting use in low-resource settings. This study adapted and evaluated the BR-ArboTrap, a low-cost trap derived from an oviposition trap, integrating a sugar-based attractant with FTA cards to collect mosquito saliva, without electricity or refrigeration. Aedes aegypti exposed to CHIKV were used in three experiments to evaluate: (i) RNA preservation under different conditions, (ii) the minimum number of positive mosquitoes for detection, and (iii) RNA amounts on FTA versus blood. RT-qPCR detected CHIKV RNA in 90% of FTA cards and 96% of exposed mosquitoes. RNA remained stable under varying conditions, with no significant difference compared to blood. BR-ArboTrap is an effective, affordable, and field-ready tool to enhance arbovirus surveillance in remote and low-resource areas. Full article

An unprecedented outbreak of Oropouche virus (OROV) is occurring in the Americas, characterized by thousands of confirmed cases and a wide geographical spread, including areas outside the Amazon Basin. Little is known about this neglected arbovirus regarding its pathophysiological aspects and potentially different transmission modes. This study describes the clinical course of a man who returned from a trip to Cuba and presented to our hospital 4 days after the onset of febrile symptoms. The patient was diagnosed with Oropouche fever and was followed for 177 days after the onset of symptoms. We performed a longitudinal investigation of the samples collected from several body sites (whole blood, serum, urine, and semen) with the aim of providing further insights into OROV infection dynamics, using the detection of antigenomic RNA as a marker of active viral replication. Clinical samples that were longitudinally collected over the course of OROV infection showed consistently higher amounts of antigenomic RNA compared to genomic RNA, even after viral clearance from serum. Moreover, our case study showed the persistence of OROV RNA in serum of less than 15 days from the onset of symptoms, as compared to up to one month in urine, three months in semen, and four months in whole blood. Our study suggests that Oropouche virus may persist in an actively replicating state in different body sites for long periods of time, with important implications for transmission dynamics. Furthermore, our results provide a diagnostic indication, suggesting that serum is inferior to both urine and whole blood as preferred diagnostic samples. Further studies are needed to determine the pathogenetic implications of these findings, as they have been derived from a single case and must be confirmed using a larger number of cases. Full article

The Oropouche virus (OROV) is an arbovirus (Peribunyaviridae: Orthobunyavirus) that traditionally causes febrile outbreaks in Latin America’s Amazon region. Previously, OROV was not associated with severe pregnancy outcomes. During the 2022–2024 outbreak in Brazil, OROV expanded geographically, revealing links to adverse pregnancy outcomes. This study describes six cases with varied fetal outcomes, including miscarriage, antepartum, intrauterine fetal demise (IFD), and normal development, correlating with maternal symptoms but not symptom severity. Vertical transmission was confirmed by detecting OROV through RT-qPCR, ELISA, and immunohistochemistry in fetal tissues. Genome sequencing from an IFD case identified a novel reassortment pattern reported in the 2022–2024 outbreak. Severe encephalomalacia, meningoencephalitis, vascular compromise, and multi-organ damage were evident, underscoring the significant risk OROV poses to fetal development and emphasizing the need for further investigation. Full article

The discovery that the Oropouche virus (OROV) can be transmitted vertically from an infected pregnant mother to the fetus, resulting in fetal and placental OROV infection, miscarriage, stillbirth, and congenital malformations including microcephaly, has emphasized its public health significance. Because of the importance of breastfeeding in those areas affected by the Oropouche fever outbreak, public health agencies have continued to encourage nursing among mothers who have had OROV infection or who reside or travel in endemic regions. However, the basis for this recommendation has not been stated. At the present time, there have been no reports of the OROV being transmitted from mothers having had Oropouche fever during pregnancy to their infants through breast milk. To further evaluate the potential risk of OROV transmission through breastfeeding, we have examined the peer-reviewed literature to determine if related Orthobunyavirus species infecting humans and animals are transmissible via breast milk. Bibliographic search engines, including PubMed, Scopus, and Google Scholar, were extensively reviewed using keywords, MeSH terms, and other sources cited in the articles examined. Studies investigating Orthobunyavirus species that infect humans and animals, including reassortant strains of OROV and viruses within the Simbu serogroup, were reviewed. We found that there have been no reported events of vertical transmission of any Orthobunyavirus through breast milk. Based on these results, we believe that the advantages of breastfeeding following maternal OROV infection outweigh any negligible risk for vertical transmission. Full article

Background: Oropouche virus (OROV), part of the Peribunyaviridae family, is an emerging pathogen causing Oropouche fever, a febrile illness endemic in South and Central America. Transmitted primarily through midge bites (Culicoides paraensis), OROV has no specific antiviral treatment or vaccine. This study aims to identify host-targeted therapeutics against OROV using computational approaches, offering a potential strategy for sustainable antiviral drug discovery. Methods: Virus-associated host targets were identified using the OMIM and GeneCards databases. The Enrichr and DSigDB platforms were used for drug prediction, filtering compounds based on Lipinski’s rule for drug likeness. A protein–protein interaction (PPI) network analysis was conducted using the STRING database and Cytoscape 3.10.3 software. Four key host targets—IL10, FASLG, PTPRC, and FCGR3A—were prioritized based on their roles in immune modulation and OROV pathogenesis. Molecular docking simulations were performed using the PyRx software to evaluate the binding affinities of selected small-molecule inhibitors—Acetohexamide, Deptropine, Methotrexate, Retinoic Acid, and 3-Azido-3-deoxythymidine—against the identified targets. Results: The PPI network analysis highlighted immune-mediated pathways such as Fc-gamma receptor signaling, cytokine control, and T-cell receptor signaling as critical intervention points. Molecular docking revealed strong binding affinities between the selected compounds and the prioritized targets, suggesting their potential efficacy as host-targeting antiviral candidates. Acetohexamide and Deptropine showed strong binding to multiple targets, indicating broad-spectrum antiviral potential. Further in vitro and in vivo validations are needed to confirm these findings and translate them into clinically relevant treatments. Conclusions: This study highlights the potential of using computational approaches to identify host-targeted therapeutics for Oropouche virus (OROV). By targeting key host proteins involved in immune modulation—IL10, FASLG, PTPRC, and FCGR3A—the selected compounds, Acetohexamide and Deptropine, demonstrate strong binding affinities, suggesting their potential as broad-spectrum antiviral candidates. Further experimental validation is needed to confirm their efficacy and potential for clinical application, offering a promising strategy for sustainable antiviral drug discovery. Full article

Oropouche orthobunyavirus (OROV) is an emerging public health concern due to its expanding geographic range and increasing case numbers. In Brazil, 13,785 cases were confirmed in 2024, with an additional 3680 reported by January 2025, according to the Ministry of Health. Initially restricted to the Amazon region, OROV has recently been detected in new areas, highlighting the need for enhanced surveillance and vector control strategies. While Culicoides paraensis is the primary vector, the potential role of other species in transmitting the currently circulating OROV strain in Brazil remains unclear. Here, we experimentally assessed the infectivity and dissemination of a recently isolated Oropouche orthobunyavirus (OROV) strain in two widespread mosquito species, Aedes aegypti and Culex quinquefasciatus, collected from diverse regions of Brazil. Our results demonstrated that both mosquito species were refractory to oral infection, suggesting that natural transmission through these vectors is unlikely. However, in artificial systemic infection, Ae. aegypti showed viral replication and immune system activation, indicating its potential to support OROV replication under specific conditions. Additionally, to assess the potential impact of coinfection, we investigated whether Chikungunya virus (CHIKV), an arbovirus that naturally infects Ae. aegypti, could facilitate OROV infection dynamics in this mosquito species. Our results suggest that coinfection does not promote OROV oral infection. Furthermore, we examined whether OROV systemic infection induced an immune response in Ae aegypti. We analyzed the major immune response pathways—RNAi, Toll, IMD, and JAK-STAT—and observed that the RNAi pathway was the most strongly activated in response to OROV infection in Ae. aegypti. These findings highlight the importance of ongoing surveillance and further studies on OROV evolution, vector adaptation, and transmission dynamics, particularly in urban settings where vector populations and viral interactions may facilitate new epidemiological scenarios. Full article

Oropouche virus (OROV) is a neglected and emerging arbovirus that infects humans and animals in South and Central America. OROV is primarily transmitted to humans through the bites of infected midges and possibly some mosquitoes. It is the causative agent of Oropouche fever, which has high morbidity but low mortality rates in humans. The disease manifests in humans as high fever, headache, myalgia, arthralgia, photophobia, and, in some cases, meningitis and encephalitis. Additionally, a recent report suggests that OROV may cause fetal death, miscarriage, and microcephaly in newborns when women are infected during pregnancy, similar to the issues caused by the Zika virus (ZIKV), another mosquito-borne disease in the same regions. OROV was first reported in the mid-20th century in the Amazon basin. Since then, over 30 epidemics and more than 500,000 infection cases have been reported. The actual case numbers may be much higher due to frequent misdiagnosis, as OROV infection presents similar clinical symptoms to other co-circulating viruses, such as dengue virus (DENV), chikungunya virus (CHIKV), ZIKV, and West Nile virus (WNV). Due to climate change, increased travel, and urbanization, OROV infections have occurred at an increasing pace and have spread to new regions, with the potential to reach North America. According to the World Health Organization (WHO), over 10,000 cases were reported in 2024, including in areas where it was not previously detected. There is an urgent need to develop vaccines, antivirals, and specific diagnostic tools for OROV diseases. However, little is known about this surging virus, and no specific treatments or vaccines are available. In this article, we review the most recent progress in understanding virology, transmission, pathogenesis, diagnosis, host–vector dynamics, and antiviral vaccine development for OROV, and provide implications for future research directions. Full article