Antiviral action of aqueous extracts of propolis from Scaptotrigona aff. postica (Hymenoptera; Apidae) against Zica, Chikungunya, and Mayaro virus.

The limited availability of antivirals for new highly pathogenic strains of virus has become a serious public health. Therefore, news products against these pathogens has become an urgent necessity. Among the multiple sources for news antibiotics and antivirals, insect exudates or their products has become an increasingly frequent option. Insects emerged 350 million years ago and have showed a high adaptability and resistance to the most varied biomes. Their survival for so long, in such different environments, is an indication that they have a very efficient protection against environmental infections, despite not having a developed immune system like mammals. Since the ancient civilizations, the products obtained from the bee have been of great pharmacological importance, being used as antimicrobial, anti-inflammatory, antitumor and several other functions. Investigations of biological activity of propolis have been carried out, mainly in the species Apis mellifera, and its product have showed activity against some important viruses. However, for the Meliponini species, known as stingless bees, there are few studies, either on their chemical composition or on their biological activities. The importance of studying these bees is because they come from regions with native forests, and therefore with many species of plants not yet studied, in addition to which they are regions still free of pesticides, which guarantees a greater fidelity of the obtained data. Previous studies by our group with crude hydroalcoholic extract of propolis demonstrated an intense antiviral activity against Herpes, influenza, and rubella viruses. In this work, we chose to use aqueous extracts, which eliminates the presence of other compounds besides those originally present in propolis, in addition to extracting substances different from those obtained in alcoholic extracts. Therefore, this study aimed to identify, isolate and characterize compounds with antiviral effects from aqueous propolis extracts from Scaptotrigona aff postica, in emerging viruses such as zicavirus, chikungunya, and mayaro virus. The evaluation of the antiviral activity of the crude and purified material was performed by reducing infectious foci in VERO cell cultures. The results obtained with crude propolis, indicate a high reduction of zica virus (64×) and mayaro (128×) when was used 10% v/v of propolis. The reduction of chikungunya virus was of 256 fold, even when was used 5% v/v of propolis. The chemical characterization of the compounds present in the extracts was performed by high-pressure liquid chromatography. Through the purification of propolis by HPLC and mass spectrometry, it was possible to identify and isolate a peak with antiviral activity. This substance showed activity against all viruses tested. When purified fraction was used, the reduction observed was of 16 fold for zicavirus, 32 fold for mayaro virus and 512 fold for chikungunya virus. Likewise, it was observed that the antiviral response was concentration dependent, being more intense when propolis was added 2 h after the viral infection. Now we are carrying out the chemical characterization of the purified compounds that showed antiviral action.

An improved alphaviruses-specific RT-qPCR facilitates monitoring and prevention of alphaviruses.

Molecular surveillance is vital for monitoring arboviruses, often employing genus-specific quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Despite this, an overlooked chikungunya fever outbreak occurred in Yunnan province, China, in 2019 and false negatives are commonly encountered during alphaviruses screening practice, highlighting the need for improved detection methods. In this study, we developed an improved alphaviruses-specific RT-qPCR capable of detecting chikungunya virus, eastern equine encephalitis virus, western equine encephalitis virus, Venezuelan equine encephalitis virus, Sindbis virus, Mayaro virus, and Ross River virus with high sensitivity and specificity. The assay identified three chikungunya virus-positive cases out of 188 sera retrospectively. Later genetic characterization suggested that imported cases from neighboring countries may be responsible for the neglected chikungunya fever outbreak of 2019 in Yunnan. Our findings underscore the value of improved alphaviruses-specific RT-qPCR in bolstering alphaviruses surveillance and informing preventive strategies.

Análise bibliométrica da produção científica global em chikungunya: perspectiva da Vigilância em Saúde / Bibliometric analysis of global scientific production on chikungunya: Health Surveillance perspective / Análisis bibliométrico de la producción científica mundial sobre chikungunya: una perspectiva de Vigilancia Sanitária

Chikungunya, arbovirose que provoca febre e artralgia debilitante, demonstra potencial crônico e incapacitante por longos períodos, não havendo vacinas ou terapias específicas. Recentemente, a doença evoluiu da condição negligenciada para uma ameaça à saúde pública, impactando milhões de pessoas em regiões tropicais e subtropicais. Este estudo analisa a produção do conhecimento sobre a Chikungunya, na perspectiva da Vigilância em Saúde. Trata-se de metodologia exploratória-descritiva, com análise bibliométrica. Realizou-se a coleta nas bases Scopus e Web of Science para artigos de 2008 a 2022. A análise revelou uma série temporal de produção destacando a contribuição de Estados Unidos, Brasil e França. Identificaram-se como áreas mais produtivas: doenças transmissíveis, medicina tropical e parasitologia, fundamentais à Vigilância em Saúde e ao planejamento de políticas públicas. Quanto aos pesquisadores, Weaver, Scott C., Failloux, Anna-Bella e De Lamballerie, Xavier foram relevantes no cenário global, indicando a importância da colaboração e da abordagem interdisciplinar.

Chikungunya, an arbovirus that causes fever and debilitating arthralgia, has potential to be chronic and incapacitating for long periods, and there are no vaccines or therapies available for it. Recently, the disease has evolved from a neglected condition to public health threat, impacting millions in tropical and subtropical regions. This study analyzed the knowledge production about chikungunya, from the perspective of Health Surveillance, using an exploratory-descriptive methodology and bibliometric analysis. Articles from 2008 to 2022 were collected from Scopus and Web of Science databases. The analysis showed a production time series, highlighting the contribution of United States, Brazil, and France. The most productive areas were identified as: communicable diseases, tropical medicine and parasitology, which are fundamental to Health Surveillance and public policy planning. Regarding researchers, Weaver, Scott C., Failloux, Anna-Bella, and De Lamballerie, Xavier were relevant in the global scenario, indicating the importance of collaboration and of the interdisciplinary approach.

El chikungunya, arbovirus que causa fiebre y artralgia debilitante, tiene potencial de ser crónico e incapacitante por largos periodos, todavía no hay vacunas ni terapias. Recientemente, la enfermedad ha pasado de afección desatendida a amenaza para la salud pública, afectando a millones en regiones tropicales y subtropicales. Este estudio analiza la producción de conocimientos sobre chikungunya, desde la perspectiva de la Vigilancia Sanitaria. Se utilizó una metodología exploratoria-descriptiva con análisis bibliométrico. Se recompilaron artículos de Scopus y Web of Science, 2008-2022. El análisis reveló una serie temporal de producción, destacando la contribución de EEUU, Brasil y Francia. Se identificaron como áreas más productivas: enfermedades transmisibles, medicina tropical y parasitología, fundamentales para la Vigilancia Sanitaria y la planificación de políticas públicas. En cuanto a los investigadores, Weaver, Scott C., Failloux, Anna-Bella y De Lamballeire, Xavier fueron relevantes en el escenario global, indicando la importancia de la colaboración y del enfoque interdisciplinario.

Halogenated Secondary Metabolites from Higher Plants: Potent Drug Candidates for Chikungunya Using in silico Approaches.

Chikungunya virus (CHIKV) causes a debilitating fever and joint pain, with no specific antiviral treatment available. Halogenated secondary metabolites from plants are a promising new class of drug candidates against chikungunya, with unique properties that make them effective against the virus. Plants produce these compounds to defend themselves against pests and pathogens, and they are effective against a wide range of viruses, including chikungunya. This study investigated the interactions of halogenated secondary metabolites with nsP2pro, a therapeutic target for CHIKV. A library of sixty-six halogenated plant metabolites screened previously for ADME properties was used. Metabolites without violation of Lipinski's rule were docked with nsP2pro using AutoDock Vina. To find the stability of the pipoxide chlorohydrin-nsP2pro complex, the GROMACS suite was used for MD simulation. The binding free energy of the ligand-protein complex was computed using MMPBSA. Molecular docking studies revealed that halogenated metabolites interact with nsP2pro, suggesting they are possible inhibitors. Pipoxide chlorohydrin showed the greatest affinity to the target. This was further confirmed by the MD simulations, surface accessible area, and MMPBSA studies. Pipoxide chlorohydrin, a halogenated metabolite, was the most potent against nsP2pro in the survey.

Co-circulation of two Alphaviruses in Burkina Faso: Chikungunya and O'nyong nyong viruses.

BACKGROUND: Chikungunya virus (CHIKV) and O'nyong nyong virus (ONNV) are phylogenetically related alphaviruses in the Semliki Forest Virus (SFV) antigenic complex of the Togaviridae family. There are limited data on the circulation of these two viruses in Burkina Faso. The aim of our study was to assess their circulation in the country by determining seroprevalence to each of the viruses in blood donor samples and by retrospective molecular and serological testing of samples collected as part of national measles and rubella surveillance. METHODOLOGY/PRINCIPAL FINDINGS: All blood donor samples were analyzed on the Luminex platform using CHIKV and ONNV E2 antigens. Patient samples collected during national measles-rubella surveillance were screened by an initial ELISA for CHIKV IgM (CHIKjj Detect IgM ELISA) at the national laboratory. The positive samples were then analyzed by a second ELISA test for CHIKV IgM (CDC MAC-ELISA) at the reference laboratory. Finally, samples that had IgM positive results for both ELISA tests and had sufficient residual volume were tested by plaque reduction neutralization testing (PRNT) for CHIKV and ONNV. These same patient samples were also analyzed by rRT-PCR for CHIKV. Among the blood donor specimens, 55.49% of the samples were positive for alphaviruses including both CHIKV and ONNV positive samples. Among patient samples collected as part of national measles and rubella surveillance, 3.09% were IgM positive for CHIKV, including 2.5% confirmed by PRNT. PRNT failed to demonstrate any ONNV infections in these samples. No samples tested by RT-qPCR. had detectable CHIKV RNA. CONCLUSIONS/SIGNIFICANCE: Our results suggest that CHIKV and ONNV have been circulating in the population of Burkina Faso and may have been confused with malaria, dengue fever or other febrile diseases such as measles or rubella. Our study underscores the necessity to enhance arbovirus surveillance systems in Burkina Faso.

Serosurvey of Chikungunya Virus in Old World Fruit Bats, Senegal, 2020-2022.

We conducted a cross-sectional serosurvey for chikungunya virus (CHIKV) exposure in fruit bats in Senegal during 2020-2023. We found that 13.3% (89/671) of bats had CHIKV IgG; highest prevalence was in Eidolon helvum (18.3%, 15/82) and Epomophorus gambianus (13.7%, 63/461) bats. Our results suggest these bats are naturally exposed to CHIKV.

Elevated Complement Activation Fragments and C1q-Binding Circulating Immune Complexes in Varied Phases of Chikungunya Virus Infection.

Chikungunya virus (CHIKV) is a causative agent of a disease continuum, ranging from an acute transient chikungunya fever to chronic incapacitating viral arthralgia. The interaction between anti-CHIKV antibodies and the complement system has recently received attention. However, the contribution of complement activation in CHIKV-induced pathologies has not been fully elucidated. The present study was undertaken to delineate the possible contribution of complement activation in CHIKV-induced disease progression. In this study, using plasma specimens of chikungunya patients in the acute, chronic, and recovered phases of infection, we explicated the involvement of complement activation in CHIKV disease progression by ELISAs and Bio-Plex assays. Correlation analysis was carried out to demonstrate interrelation among C1q-binding IgG-containing circulating immune complexes (CIC-C1q), complement activation fragments (C3a, C5a, sC5b-9), and complement-modulated pro-inflammatory cytokines (IL-1ß, IL-18, IL-6, and TNF-α). We detected elevated complement activation fragments, CIC-C1q, and complement-modulated cytokines in the varied patient groups compared with the healthy controls, indicating persistent activation of the complement system. Furthermore, we observed statistically significant correlations among CIC-C1q with complement activation fragments and C3a with complement modulatory cytokines IL-1ß, IL-6, and IL-18 during the CHIKV disease progression. Taken together, the current data provide insight into the plausible association between CICs, complement activation, subsequent complement modulatory cytokine expression, and CHIKV etiopathology.

Evaluation of Multiple RNA Extraction Protocols for Chikungunya Virus Screening in Aedes aegypti Mosquitoes.

Chikungunya virus (Togaviridae, Alphavirus; CHIKV) is a mosquito-borne global health threat. The main urban vector of CHIKV is the Aedes aegypti mosquito, which is found throughout Brazil. Therefore, it is important to carry out laboratory tests to assist in the virus's diagnosis and surveillance. Most molecular biology methodologies use nucleic acid extraction as the first step and require quality RNA for their execution. In this context, four RNA extraction protocols were evaluated in Ae. aegypti experimentally infected with CHIKV. Six pools were tested in triplicates (n = 18), each containing 1, 5, 10, 20, 30, or 40 mosquitoes per pool (72 tests). Four commercial kits were compared: QIAamp®, Maxwell®, PureLink®, and PureLink® with TRIzol®. The QIAamp® and PureLink® with TRIzol® kits had greater sensitivity. Two negative correlations were observed: as the number of mosquitoes per pool increases, the Ct value decreases, with a higher viral load. Significant differences were found when comparing the purity and concentration of RNA. The QIAamp® protocol performed better when it came to lower Ct values and higher RNA purity and concentration. These results may provide help in CHIKV entomovirological surveillance planning.

Clinical outcomes of chikungunya: A systematic literature review and meta-analysis.

BACKGROUND: Chikungunya is a viral disease caused by a mosquito-borne alphavirus. The acute phase of the disease includes symptoms such as fever and arthralgia and lasts 7-10 days. However, debilitating symptoms can persist for months or years. Despite the substantial impact of this disease, a comprehensive assessment of its clinical picture is currently lacking. METHODS: We conducted a systematic literature review on the clinical manifestations of chikungunya, their prevalence and duration, and related hospitalization. Embase and MEDLINE were searched with no time restrictions. Subsequently, meta-analyses were conducted to quantify pooled estimates on clinical outcomes, the symptomatic rate, the mortality rate, and the hospitalization rate. The pooling of effects was conducted using the inverse-variance weighting methods and generalized linear mixed effects models, with measures of heterogeneity reported. RESULTS: The systematic literature review identified 316 articles. Out of the 28 outcomes of interest, we were able to conduct 11 meta-analyses. The most prevalent symptoms during the acute phase included arthralgia in 90% of cases (95% CI: 83-94%), and fever in 88% of cases (95% CI: 85-90%). Upon employing broader inclusion criteria, the overall symptomatic rate was 75% (95% CI: 63-84%), the chronicity rate was 44% (95% CI: 31-57%), and the mortality rate was 0.3% (95% CI: 0.1-0.7%). The heterogeneity between subpopulations was more than 92% for most outcomes. We were not able to estimate all predefined outcomes, highlighting the existing data gap. CONCLUSION: Chikungunya is an emerging public health concern. Consequently, a thorough understanding of the clinical burden of this disease is necessary. Our study highlighted the substantial clinical burden of chikungunya in the acute phase and a potentially long-lasting chronic phase. Understanding this enables health authorities and healthcare professionals to effectively recognize and address the associated symptoms and raise awareness in society.

A 44-Nucleotide Region in the Chikungunya Virus 3' UTR Dictates Viral Fitness in Disparate Host Cells.

We previously reported that deletion of a 44-nucleotide element in the 3' untranslated region (UTR) of the Chikungunya virus (CHIKV) genome enhances the virulence of CHIKV infection in mice. Here, we find that while this 44-nucleotide deletion enhances CHIKV fitness in murine embryonic fibroblasts in a manner independent of the type I interferon response, the same mutation decreases viral fitness in C6/36 mosquito cells. Further, the fitness advantage conferred by the UTR deletion in mammalian cells is maintained in vivo in a mouse model of CHIKV dissemination. Finally, SHAPE-MaP analysis of the CHIKV 3' UTR revealed this 44-nucleotide element forms a distinctive two-stem-loop structure that is ablated in the mutant 3' UTR without altering additional 3' UTR RNA secondary structures.

Accurate Recapitulation of Chikungunya Virus Complete Coding Sequence Phylogeny Using Variable Genome Regions for Genomic Surveillance.

Chikungunya virus (CHIKV) is transmitted by mosquito bites and causes chikungunya fever (CHIKF). CHIKV has a single-stranded RNA genome and belongs to a single serotype with three genotypes. The Asian lineage has recently emerged in the Western Hemisphere, likely due to travel-associated introduction. Genetic variation accumulates in the CHIKV genome as the virus replicates, creating new lineages. Whole genome sequencing is ideal for studying virus evolution and spread but is expensive and complex. This study investigated whether specific, highly variable regions of the CHIKV genome could recapitulate the phylogeny obtained with a complete coding sequence (CDS). Our results revealed that concatenated highly variable regions accurately reconstructed CHIKV phylogeny, exhibiting statistically indistinguishable branch lengths and tree confidence compared to CDS. In addition, these regions adequately inferred the evolutionary relationships among CHIKV isolates from the American outbreak with similar results to the CDS. This finding suggests that highly variable regions can effectively capture the evolutionary relationships among CHIKV isolates, offering a simpler approach for future studies. This approach could be particularly valuable for large-scale surveillance efforts.

Elucidation of the Epitranscriptomic RNA Modification Landscape of Chikungunya Virus.

The genomes of positive-sense (+) single-stranded RNA (ssRNA) viruses are believed to be subjected to a wide range of RNA modifications. In this study, we focused on the chikungunya virus (CHIKV) as a model (+) ssRNA virus to study the landscape of viral RNA modification in infected human cells. Among the 32 distinct RNA modifications analysed by mass spectrometry, inosine was found enriched in the genomic CHIKV RNA. However, orthogonal validation by Illumina RNA-seq analyses did not identify any inosine modification along the CHIKV RNA genome. Moreover, CHIKV infection did not alter the expression of ADAR1 isoforms, the enzymes that catalyse the adenosine to inosine conversion. Together, this study highlights the importance of a multidisciplinary approach to assess the presence of RNA modifications in viral RNA genomes.

Seroprevalence of Arboviruses in a Malaria Hyperendemic Area in Southern Mali.

Diagnostics for febrile illnesses other than malaria are not readily available in rural sub-Saharan Africa. This study assessed exposure to three mosquito-borne arboviruses-dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV)-in southern Mali. Seroprevalence for DENV, CHIKV, and ZIKV was analyzed by detection of IgG antibodies and determined to be 77.2%, 31.2%, and 25.8%, respectively. Among study participants, 11.3% were IgG-positive for all three arboviruses. DENV had the highest seroprevalence rate at all sites; the highest seroprevalence of CHIKV and ZIKV was observed in Bamba. The seroprevalence for all three arboviruses increased with age, and the highest seroprevalence was observed among adults older than 50 years. The prevalence of Plasmodium spp. in the cohort was analyzed by microscopy and determined to be 44.5% (N = 600) with Plasmodium falciparum representing 95.1% of all infections. This study demonstrates the co-circulation of arboviruses in a region hyperendemic for malaria and highlights the needs for arbovirus diagnostics in rural sub-Saharan Africa.

Molecular surveillance for dengue serotypes among the population living in Moyen-Ogooué province, Gabon; evidence of the presence of dengue serotype 1.

BACKGROUND: Despite dengue virus (DENV) outbreak in Gabon a decade ago, less is known on the potential circulation of DENV serotypes in the country. Previous studies conducted in some areas of the country, are limited to hospital-based surveys which reported the presence of some cases of serotype 2 and 3 seven years ago and more recently the serotype 1. As further investigation, we extend the survey to the community of Moyen Ogooué region with the aim to assess the presence of the dengue virus serotypes, additionally to characterize chikungunya (CHIKV) infection and describe the symptomatology associated with infections. METHOD: A cross-sectional survey was conducted from April 2020 to March 2021. The study included participants of both sexes and any age one year and above, with fever or history of fever in the past seven days until blood collection. Eligible volunteers were clinically examined, and blood sample was collected for the detection of DENV and CHIKV using RT-qPCR. Positive samples were selected for the target sequencing. RESULTS: A total of 579 volunteers were included. Their mean age (SD) was 20 (20) years with 55% of them being female. Four cases of DENV infection were diagnosed giving a prevalence of 0.7% (95%CI: 0.2-1.8) in our cohort while no case of CHIKV was detected. The common symptoms and signs presented by the DENV cases included fatigue, arthralgia myalgia, cough, and loss of appetite. DENV-1was the only virus detected by RT-qPCR. CONCLUSION: Our results confirm the presence of active dengue infection in the region, particularly DENV-1, and could suggest the decline of DENV-2 and DENV-3. Continuous surveillance remains paramount to comprehensively describe the extent of dengue serotypes distribution in the Moyen-Ogooué region of Gabon.

Explorations on the antiviral potential of zinc and magnesium salts against chikungunya virus: implications for therapeutics.

Background: Chikungunya virus (CHIKV), which causes chikungunya fever, is an arbovirus of public health concern with no approved antiviral therapies. A significant proportion of patients develop chronic arthritis after an infection. Zinc and magnesium salts help the immune system respond effectively against viral infections. This study explored the antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV infection. Methods: The highest non-toxic concentration of the salts (100 µM) was used to assess the prophylactic, virucidal, and therapeutic anti-CHIKV activities. Dose-dependent antiviral effects were investigated to find out the 50% inhibitory concentration of the salts. Entry bypass assay was conducted to find out whether the salts affect virus entry or post entry stages. Virus output in all these experiments was estimated using a focus-forming unit assay, real-time RT-PCR, and immunofluorescence assay. Results: Different time- and temperature-dependent assays revealed the therapeutic antiviral activity of zinc and magnesium salts against CHIKV. A minimum exposure of 4 hours and treatment initiation within 1 to 2 hours of infection are required for inhibition of CHIKV. Entry assays revealed that zinc salt affected virus-entry. Entry bypass assays suggested that both salts affected post-entry stages of CHIKV. In infected C57BL6 mice orally fed with zinc and magnesium salts, a reduction in viral RNA copy number was observed. Conclusion: The study results suggest zinc salts exert anti-CHIKV activity at entry and post entry stages of the virus life cycle, while magnesium salt affect CHIKV at post entry stages. Overall, the study highlights the significant antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV, which can be exploited in designing potential therapeutic strategies for early treatment of chikungunya patients, thereby reducing the virus-associated persistent arthritis.

Vertical transmission of chikungunya virus: a worldwide concern.

The Chikungunya Virus (CHIKV) already has endemic circulation in about 100 countries and the number of infected patients increases every year, due to the effectiveness of the vector and human universal susceptibility to infection. The virus can also be transmitted from mother to child, more frequently intrapartum. About 50 % of neonates with CHIKV symptoms will have neurodevelopmental delay. It is therefore an infection of worldwide concern with a great impact on people's quality of life. The objective of this work is to describe two cases of confirmed vertical transmission by chikungunya virus, one of them with intrauterine infection and death of the neonate. Neonates with vertical chikungunya infection may present with clinical sepsis in the first few days of life, which is why this is a very important diagnosis, especially during outbreaks of the infection.

4'-Fluorouridine inhibits alphavirus replication and infection in vitro and in vivo.

Chikungunya virus (CHIKV) is an enveloped, positive-sense RNA virus that has re-emerged to cause millions of human infections worldwide. In humans, acute CHIKV infection causes fever and severe muscle and joint pain. Chronic and debilitating arthritis and joint pain can persist for months to years. To date, there are no approved antivirals against CHIKV. Recently, the ribonucleoside analog 4'-fluorouridine (4'-FlU) was reported as a highly potent orally available inhibitor of SARS-CoV-2, respiratory syncytial virus, and influenza virus replication. In this study, we assessed 4'-FlU's potency and breadth of inhibition against a panel of alphaviruses including CHIKV, and found that it broadly suppressed alphavirus production in cell culture. 4'-FlU acted on the viral RNA replication step, and the first 4 hours post-infection were the critical time for its antiviral effect. In vitro replication assays identified nsP4 as the target of inhibition. In vivo, treatment with 4'-FlU reduced disease signs, inflammatory responses, and viral tissue burden in mouse models of CHIKV and Mayaro virus infection. Treatment initiated at 2 hours post-infection was most effective; however, treatment initiated as late as 24-48 hours post-infection produced measurable antiviral effects in the CHIKV mouse model. 4'-FlU showed effective oral delivery in our mouse model and resulted in the accumulation of both 4'-FlU and its bioactive triphosphate form in tissues relevant to arthritogenic alphavirus pathogenesis. Together, our data indicate that 4'-FlU inhibits CHIKV infection in vitro and in vivo and is a promising oral therapeutic candidate against CHIKV infection.IMPORTANCEAlphaviruses including chikungunya virus (CHIKV) are mosquito-borne positive-strand RNA viruses that can cause various diseases in humans. Although compounds that inhibit CHIKV and other alphaviruses have been identified in vitro, there are no licensed antivirals against CHIKV. Here, we investigated a ribonucleoside analog, 4'-fluorouridine (4'-FlU), and demonstrated that it inhibited infectious virus production by several alphaviruses in vitro and reduced virus burden in mouse models of CHIKV and Mayaro virus infection. Our studies also indicated that 4'-FlU treatment reduced CHIKV-induced footpad swelling and reduced the production of pro-inflammatory cytokines. Inhibition in the mouse model correlated with effective oral delivery of 4'-FlU and accumulation of both 4'-FlU and its bioactive form in relevant tissues. In summary, 4'-FlU exhibits potential as a novel anti-alphavirus agent targeting the replication of viral RNA.

Tracing the evolution of the chikungunya virus in Argentina, 2016-2023: independent introductions and prominence of Latin American lineages.

Chikungunya virus (CHIKV) has emerged as a significant public health concern due to its rapid spread and potential for causing debilitating epidemics. In Argentina, the virus has garnered attention since its introduction to the Americas in 2013, due to its growing incidence and impact in neighbouring countries. Here we present a comprehensive analysis of the spatiotemporal dynamics of CHIKV in Argentina, focusing on the evolutionary trajectory of its genetic variants. Through a combination of active surveillance, screening of historical and recent samples, and whole-genome sequencing, we traced the evolutionary history of CHIKV lineages circulating within the country. Our results reveal that two distinct genotypes circulated in Argentina: The Asian lineage during the 2016 epidemic and the ECSA lineage in 2023. This distribution reflects the dominance of particular variants across Latin America. Since 2023, the ECSA lineage has led to a surge in cases throughout the Americas, marking a significant shift. The replacement of lineages in the American region constitutes a major epidemiological event, potentially affecting the dynamics of virus transmission and the clinical outcomes in impacted populations. The spatiotemporal analysis highlights CHIKV's distribution across Argentina and underscores the significant role of human mobility, especially when considering recent epidemics in neighbouring countries such as Paraguay and Uruguay, which have facilitated the spread and introduction of the viral strain into different districts. By integrating epidemiological data with genomic insights, we elucidate the patterns of virus dissemination, highlighting key areas of transmission and potential factors contributing to its spread.

Exploring the Chikungunya virus landscape in a dengue-endemic Brazilian area.

We aimed to describe the landscape, including molecular, epidemiological, and clinical aspects of CHIKV infections in the Ribeirao Preto region, an area endemic to dengue. We randomly screened 3744 plasma samples that had undergone DENV diagnosis to evaluate CHIKV-RNA using an in-house RT-PCR assay. Positive samples were followed clinically, and RNA samples were submitted to whole genome sequencing. Seventeen cases (0.5 %) were positive for CHIKV-RNA despite being negative for DENV-RNA. Notably, half of the patients experienced prolonged arthralgia lasting more than 90 days. Compared with the healthy control group, leukopenia and thrombocytopenia were observed in all CHIKV-positive individuals with statistically significant P values (P < 0.0001 and P = 0.0003, respectively). The genomic analysis revealed that the CHIKV strains being studied are classified within the East-Central-South-African (ECSA) genotype. This analysis identified new mutations, E1: K211E and E2: V264A, while the previously known mutation E1: A226V was not detected among these strains. This study highlights the need for epidemiological surveillance and preparedness for potential CHIKV epidemics in Brazil, particularly where other arboviruses co-circulate.