Search Results (66)

Arthropod-borne viruses (arboviruses) are an increasingly significant threat to public health in tropical regions. In this study, we investigated the seroprevalence of various arboviruses in two species of sloth (Choloepus hoffmanni and Bradypus variegatus) in rural and peri-urban areas of Western Panama province. Between 2013 and 2018, blood samples from 60 sloths were tested for neutralizing antibodies against ten arboviruses. Significant variation in seroprevalence of different arboviruses was observed: 6.7% of sloths were seropositive for Madariaga virus, 6.7% for Venezuelan equine encephalitis virus, and 4.8% for Oropouche virus, while none were seropositive for dengue type 2, Zika, chikungunya, Una, Mayaro, or Punta Toro viruses. Notably, two Changuinola virus (CGLV) strains, which were previously isolated from Panamanian sloths in the 1970s, showed high seroprevalence: Pansloth 149 (23.3%) and D50 (53.3%). Given the high seroprevalence detected in our study and the lack of genomic characterization of the historical Pansloth 149 isolate, we performed next-generation sequencing of its complete genome using Illumina technology to understand its genetic diversity and evolutionary relationship with other CGLV strains. 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

Mayaro virus (MAYV) is an alphavirus transmitted by mosquito vectors. Among the three MAYV genotypes (D, L, and N), genotype D has the broadest geographical distribution in Latin America and the Caribbean. The virus can be transmitted by the Aedes, Anopheles, and Haemagogus mosquitoes. To explore the potential expansion of MAYV across the Atlantic Ocean, we compared MAYV (D) infection kinetics in Floridian Aedes aegypti with New World (Anopheles albimanus) and Old World (Anopheles gambiae) anophelines. MAYV infection of both An. albimanus and An. gambiae was rapid, resulting in a higher dissemination rate than Ae. aegypti. We detected MAYV in saliva from An. albimanus (16.6% transmission rate) as early as 2 days post-infection (dpi), increasing to 60% after 7 dpi, a phenomenon (2 dpi) that has not been described to date for mosquitoes. We observed similar increases in MAYV infection of the ovaries and noted marked differences in fecundity for each species tested. Although MAYV infection in An. gambiae was rapid, mosquito lifespan was significantly reduced as compared with both Ae. aegypti and An. albimanus. We discuss the implications of our observations on MAYV transmission risk in Africa by An. gambiae and in the Caribbean and Central America by An. albimanus. Full article

Dengue, Zika, yellow fever, chikungunya, and Mayaro arboviruses represent an increasing threat to public health because of the serious infections they cause annually in many countries. Serological diagnosis of these viruses is challenging, making the development of new diagnostic strategies imperative. In this study, we investigated the effectiveness of gold nanorods (GNRs) functionalized with specific anti-dengue and anti-orthoflavivirus antibodies in detecting viral particles. GNRs were created with a length-to-width ratio of up to 5.5, a size of 71.4 ± 6.5 nm, and a light absorption peak at 927 nm, and they were treated with 4 mM polyethyleneimine. These GNRs were attached to a small amount of monoclonal antibodies that target flaviviruses, and the viral particles were detected by measuring the localized surface plasmon resonance using an UV-Vis/NIR spectrometer. The tests found Orthoflavivirus dengue and Orthoflavivirus zikaense in diluted human serum and ground-up mosquitoes, with the lowest detectable amount being 100 PFU/mL. The GNRs described in this study can be used to enhance flavivirus diagnostic tests or to develop new, faster, and more accurate diagnostic techniques. Additionally, the functionalized GNRs presented here are promising for supporting virological surveillance studies in mosquitoes. Our findings highlight a fast and highly sensitive method for detecting Orthoflavivirus in both human and mosquito samples, with a detection limit as low as 100 PFU/mL. Full article

Polyphenols are structurally diverse plant metabolites that have attracted significant interest. Their compositions are versatile, depending on their structures, including the number of rings in the polyphenol composition. Based on these attributes, polyphenols can be classified as flavanols, anthocyanins, flavones, phenolic acids, stilbenes, and lignans. Polyphenols mainly possess inhibition of viral replication, interference with viral protein synthesis, and modulation of immune responses, providing significant antiviral effects against several viruses, including herpes simplex virus, hepatitis C virus, and influenza. They are crucial for medical compounds in diverse, versatile treatments, namely in diabetes, cardiovascular disorders, cancer, and neurodegenerative problems. Plants are the primary source of bioactive molecules, which are valued for their anti-inflammatory, antioxidant, anticancer, and antiviral activities. Especially, polyphenols are extracted as the most abundant bioactive compounds of plants. Moreover, viral infections are one of the major factors in illnesses and diseases, along with bacteria and fungi. Numerous in vitro and in vivo studies report antiviral activity against SARS-CoV-2, Mayaro virus, dengue virus, herpesvirus, and influenza A virus, though clinical validation remains limited. Additionally, inhibition of viral entry, interference with viral replication, modulation of host immune response, and direct virucidal effects were examined. Full article

The Aedes aegypti mosquito is a vector for several arboviral diseases, posing a significant threat to human populations and exacerbating health disparities. Puerto Rico is a subtropical region where A. aegypti mosquitoes circulate all the year promoting the transmission of arboviruses. A cross-sectional study in the municipality of Ponce, Puerto Rico was conducted to determine the prevalence of arbovirus in A. aegypti mosquitoes and community members, and the impact that sociodemographic and environmental factors on the presence of arbovirus in the community. Our results indicate that more than a third of the population has long-term antibodies (IgG) against chikungunya and the Mayaro virus (56% and 17%, respectively). In addition, more than two-thirds of the population have long-term antibodies (IgG) against dengue and Zika virus (96.0% and 77%, respectively). Dengue virus 1 (DENV-1) was only detected in mosquitoes from urban areas. The practice of storing water in containers uncovered and living near a river increased the odds of having arbovirus in the community (OR = 3.5, 95% CI = 1.8–10.6) (p < 0.05) and (OR = 1.6, 95% CI = 1.2–3.7). Furthermore, lower income was a social determinant associated with being at risk of arboviral disease in the communities (OR = 2.9, 95% CI = 1.4–8.5) (p < 0.05). It is recommended that public health activities be implemented, including education workshops on prevention and health promotion and health services such as vector control, to prevent arboviral diseases in communities. Full article

Background/objectives: In Brazil, the co-circulation of arboviruses—such as dengue, Zika, yellow fever, and Chikungunya viruses—creates a complex epidemiological landscape, drawing attention from health authorities due to high morbidity and mortality rates. Also present in this context is the Mayaro virus (MAYV), a neglected arbovirus, which can also cause severe syndromes and has been expanding beyond its usual endemic areas in northern and central-western Brazil. Epidemiological surveillance measures remain limited, and there are no effective prophylactic strategies or antiviral treatments for this neglected arbovirus. In this study, we evaluated the antiviral activity of commercial and synthetic compounds against MAYV using an image high-throughput screening (iHTS) system. Methods: A total of 52 compounds from an FDA-approved commercial library (Tocriscreen) and 50 other compounds were tested. Results: Seven compounds showed anti-MAYV activity and were non-toxic for the following cell lines: Naringenin, LLA9A, chrysin, and its ester C6. Post-infection treatments with these selected compounds significantly decreased the percentage of infected cells and the release of infectious viral particles in the supernatant. Additionally, anti-MAYV activity of these four selected hits was confirmed using several human cell lines and two different MAYV genotypes. Conclusions: Our results indicate that the iHTS platform is effective for screening anti-MAYV drugs and that four promising compounds can efficiently inhibit MAYV replication in human cell lines. Although in vivo studies are still required to confirm the efficacy of the selected hits, our findings provide a starting point for developing a potential treatment for MAYV infections. Full article

Aedes aegypti is a major vector of arboviruses, including dengue, Zika, chikungunya, yellow fever, and Mayaro. The extensive use of insecticides has led to resistance, complicating vector control efforts. MicroRNAs (miRNAs) are post-transcriptional regulators involved in detoxification and stress adaptation; however, their role in the insecticide response of Ae. aegypti remains unclear. This study analyzed miRNA expression in Ae. aegypti following imidacloprid exposure, comparing a field strain, Martinez de la Torre from Mexico (MT), and a susceptible reference strain, New Orleans (NO). Small RNA sequencing identified 96 miRNAs, with miR-1, miR-281-5p, miR-100, and miR-184 being consistently expressed across all conditions. In contrast, let-7, miR-124, and miR-13-3p were exclusively detected in wild mosquitoes exposed to imidacloprid, while miR-14 and miR-275-3p showed condition-specific expression. Distinct miRNA expression patterns were observed between the field and susceptible strains, with specific miRNAs showing condition-dependent expression. These findings suggest that certain miRNAs may serve as potential biomarkers for resistance monitoring, contributing to a better understanding of insecticide response mechanisms and informing novel vector control strategies. Full article

Chikungunya virus (CHIKV) and other alphaviruses that primarily induce arthritogenic disease in humans, known as “Old World” alphaviruses, present an emerging public health concern as geographic ranges of mosquito vectors expand due to climate change. While a vaccine against CHIKV has recently been approved by several countries in North America and Europe, access to effective preventative countermeasures against disease induced by Old World alphaviruses remains elusive for the most vulnerable populations. Furthermore, treatment options continue to be limited to supportive care. Atypical neurological disease manifestations caused by Old World alphaviruses, which make up as many as 25% of the cases in some CHIKV outbreaks, present special challenges when considering strategies for developing effective countermeasures. This review focuses on Old World alphaviruses, specifically CHIKV, Ross River virus, O’nyoug-nyoug virus, and Mayaro virus, concentrating on the atypical neurological disease manifestations they may cause. Our current understanding of Old World alphavirus neuropathogenesis, gained from human cases and preclinical animal models, is discussed, including viral and host factors’ roles in disease development. The current state of alphavirus preventatives and treatments, both virus-targeting and host-directed therapies, is then summarized and discussed in the context of addressing neurological disease induced by Old World alphaviruses. Full article

The Mayaro virus (MAYV), Togaviridae family, genus Alphavirus, has caused several sporadic outbreaks, affecting countries in the Americas. Currently, there are no licensed drugs against MAYV, requiring the search for effective antiviral compounds. Thus, this study aimed to evaluate the antiviral potential of polyphenol (-)-epigallocatechin-3-gallate (EGCG) against MAYV infection, in vitro. Antiviral assays against MAYV were performed in BHK-21 and Vero E6 cells. In addition, molecular docking was performed with EGCG and the MAYV non-structural and structural proteins. EGCG showed a significant protective effect against MAYV infection in both cell lines. The virucidal assay showed an effect on extracellular viral particles at the entry stage into BHK-21 cells. Finally, it also showed significant inhibition in the post-entry stages of the MAYV replication cycle, acting on the replication of the genetic material and late stages, such as assembly and release. In addition, the MAYV proteins E1 and nsP1 were significantly inhibited by the EGCG treatment in BHK-21 cells. Molecular docking analysis also showed that EGCG could interact with MAYV Capsid and Envelope proteins (E1 and E2). Therefore, this study shows the potential of EGCG as a promising antiviral against MAYV, as it acts on different stages of the MAYV replication cycle. Full article

Background: Vector-borne diseases, such as leishmaniasis and arboviral infections, represent a great challenge to human health with limited therapeutic options. In addition, sexually transmitted infections, such as herpes, affect billions of people worldwide and the emergence of new strains resistant to common antivirals, such as acyclovir (ACV), poses a serious threat to humans. In this context, coumarins have proved to be a valuable source of new derivatives with promising biological activities to fight these diseases. Methodology: 3-aryl and/or 4-(N-aryl)aminocoumarins were synthesized, and their drug-like profile was evaluated using silico tools. Their biological activity against Leishmania amazonensis promastigotes was evaluated using the MTT assay, while their antiviral activity against replication of Chikungunya, Mayaro, Zika, and type 1 Herpes simplex virus (HSV-1) in Vero cells was analyzed using plaque reduction assays. Results: The in silico studies pointed to satisfactory pharmacokinetic and toxicological properties as drug candidates. Hence, their antileishmanial activity was evaluated. None of the compounds exhibited significant activity and compound 2b showed the highest activity (IC₅₀ = 47.10 µM). We further evaluated their cytotoxicity and antiviral activity. Compound 2e showed good activity against ACV-sensitive and -resistant HSV-1 strains with EC₅₀ values of 48.68 µM and 66.26 µM, respectively (selectivity index values of 12.5 and 9.2). Mechanism of action studies indicated that this compound acts at late steps of HSV-1 replication, such as virus egress. Conclusions: Compound 2e possesses a different mechanism of action compared to ACV and presents a promising alternative for the treatment of HSV-1 infections. Full article

Chikungunya and Mayaro fevers are viral infectious diseases characterized by fever and arthralgia, for which there are currently no effective vaccines or treatments. The urgent need for novel antiviral agents against Chikungunya virus (CHIKV) and Mayaro virus (MAYV) has led to interest in plant-based compounds that can disrupt the viral replication cycle. Chiococca alba (L.) Hitchc., a Neotropical plant traditionally used by Yucatec Maya healers as an antipyretic and antirheumatic, may hold potential as a source of antiviral agents. This study aimed to evaluate the antiviral potential of C. alba methanolic extracts (CAH21 and CAH24) against CHIKV and MAYV through preliminary in vitro and in silico analyses. The cytotoxicity of two methanolic extracts from C. alba roots was assessed in Vero cells using the neutral red assay, and their viral activity was determined via plaque assay post-treatment. Given the observed antiviral effects, we used computational predictions to explore interactions between the multifunctional nsP2 proteases and secondary metabolites identified in C. alba extracts. The metabolites were identified using high-performance liquid chromatography (HPLC) and gas chromatography–mass spectrometry (GC-MS). Phytochemical analysis revealed the presence of flavonoids, coumarins, and phenolic acids in the C. alba extracts. In vitro assays demonstrated that both extracts inhibited over 70% of activity against CHIKV and MAYV at a concentration of 60 µg/mL. In silico predictions suggested that the flavonoids naringin and vitexin had the highest affinity for the nsP2 proteases of CHIKV and MAYV, indicating their potential as viral inhibitors. Our findings revealed that C. alba extract represents a promising source of novel antiviral compounds. Full article

Chikungunya virus (CHIKV) is a pathogenic arthritogenic alphavirus responsible for large-scale human epidemics for which a vaccine was recently approved for use. Mayaro virus (MAYV) is a related emerging alphavirus with epidemic potential with circulation overlap potential with CHIKV. We previously reported the ability of a non-replicating human adenovirus (AdV)-vectored vaccine expressing the MAYV structural polyprotein to protect against disease in mice following challenge with MAYV, CHIKV and UNAV. Herein, we evaluated mouse immunity and protective efficacy for an AdV-CHIKV full structural polyprotein vaccine in combination with heterologous AdV-MAYV prime/boost regimens versus vaccine coadministration. Heterologous prime/boost regimens skewed immunity toward the prime vaccine antigen but allowed for a boost of cross-neutralizing antibodies, while vaccine co-administration elicited robust, balanced responses capable of boosting. All immunization strategies protected against disease from homologous virus infection, but reciprocal protective immunity differences were revealed upon challenge with heterologous viruses. In vivo passive transfer experiments reproduced the inequity in reciprocal cross-protection after heterologous MAYV challenge. We detected in vitro antibody-dependent enhancement of MAYV replication, suggesting a potential mechanism for the lack of cross-protection. Our findings provide important insights into rational alphavirus vaccine design that may have important implications for the evolving alphavirus vaccine landscape. Full article

Chikungunya (CHIKV) and Mayaro (MAYV) viruses are arthritogenic alphaviruses that promote an incapacitating and long-lasting inflammatory muscle–articular disease. Despite studies pointing out the importance of skeletal muscle (SkM) in viral pathogenesis, the long-term consequences on its physiology and the mechanism of persistence of symptoms are still poorly understood. Combining molecular, morphological, nuclear magnetic resonance imaging, and histological analysis, we conduct a temporal investigation of CHIKV and MAYV replication in a wild-type mice model, focusing on the impact on SkM composition, structure, and repair in the acute and late phases of infection. We found that viral replication and induced inflammation promote a rapid loss of muscle mass and reduction in fiber cross-sectional area by upregulation of muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1 expression, both key regulators of SkM fibers atrophy. Despite a reduction in inflammation and clearance of infectious viral particles, SkM atrophy persists until 30 days post-infection. The genomic CHIKV and MAYV RNAs were still detected in SkM in the late phase, along with the upregulation of chemokines and anti-inflammatory cytokine expression. In agreement with the involvement of inflammatory mediators on induced atrophy, the neutralization of TNF and a reduction in oxidative stress using monomethyl fumarate, an agonist of Nrf2, decreases atrogen expression and atrophic fibers while increasing weight gain in treated mice. These data indicate that arthritogenic alphavirus infection could chronically impact body SkM composition and also harm repair machinery, contributing to a better understanding of mechanisms of arthritogenic alphavirus pathogenesis and with a description of potentially new targets of therapeutic intervention. Full article

Mayaro virus (MAYV) is an arbovirus first isolated in Trinidad and Tobago in 1954. MAYV is the causative agent of Mayaro fever, which is characterised by high fever, maculopapular rash, myalgia and arthralgia. The potential for chronic arthralgia is of particular clinical concern. Currently, MAYV outbreaks are restricted to South and Central America, with some cases reported in Africa as well as several imported cases in Europe. However, in recent years, MAYV has become a growing global concern due to its potential to emerge into urban transmission cycles. Challenges faced with diagnostics, as well as a lack of specific antivirals or licensed vaccines further exacerbate the potential global health threat posed by MAYV. In this review, we discuss this emerging arboviral threat with a particular focus on the current treatment and vaccine development efforts. Overall, MAYV remains a neglected arbovirus due to its limited area of transmission. However, with the potential of its urbanisation and expanding circulation, the threat MAYV poses to global health cannot be overlooked. Further research into the improvement of current diagnostics, as well as the development of efficacious antivirals and vaccines will be crucial to help prevent and manage potential MAYV outbreaks. Full article