First report of laboratory-confirmed Zika virus infection in human from South Karnataka, India: A case study.

Introduction: The Zika virus (ZIKV), transmitted primarily by Aedes mosquitoes, has caused significant public health concern due to its association with congenital abnormalities, including microcephaly, and neurological disorders such as Guillain-Barré syndrome. It was first discovered in Uganda in 1947, with its most significant global outbreak occurring between 2015 and 2016. Methodology: A comprehensive literature review was conducted using PubMed, Scopus, the World Health Organization (WHO), and the Centers for Disease Control and Prevention (CDC) databases, covering the period from 2000 to 2024. The search strategy incorporated relevant keywords such as “Zika virus,” “ZIKV epidemiology,” “ZIKV vaccine,” “Aedes mosquitoes,” and “Zika congenital syndrome.” Results: The Zika virus primarily spreads via Aedes mosquitoes, with sexual and congenital transmission also contributing to its spread. The virus has posed significant public health challenges, particularly among pregnant women, resulting in birth defects. Recent data from India highlights an increase in Zika virus cases, especially in Maharashtra and Karnataka. Current preventive measures include vector control, safe sexual practices, and public health campaigns; however, a vaccine is still under development. Discussion: Despite global efforts, the Zika virus continues to threaten maternal and neonatal health, particularly in endemic regions. Its resurgence in areas like India signals the need for proactive containment and education strategies. Conclusion: The Zika virus remains a serious global health threat. There is an urgent need for continued surveillance, effective prevention strategies, and vaccine development to mitigate its impact. Enhanced public awareness and ongoing research are critical to managing Zika-related health risks.

Arboviral burden among pregnant women with HIV coinfection in sub-Saharan Africa remains inadequately characterised. To assess arboviral seroprevalence using IgG and IgM antibodies to distinguish historical exposure from relatively recent infection among Nigerian women. We conducted a cross-sectional serosurvey (December 2020-November 2023) across three Nigerian regions representing distinct ecological zones, recruiting 619 women: HIV-positive pregnant (n = 207), HIV-negative pregnant (n = 207), and HIV-positive non-pregnant (n = 205). Arboviral IgG and IgM antibodies against chikungunya virus (CHIKV), dengue virus (DENV), Zika virus (ZIKV), and other flaviviruses were detected using immunoblot assays, with plaque reduction neutralisation testing (PRNT) performed on a subset of 150 samples to support virus-specific interpretation. IgG seropositivity was highest for CHIKV (42.2%), followed by DENV (27.1%) and ZIKV (13.6%). IgM seropositivity, indicating relatively recent infection, was observed for CHIKV (14.1%), DENV (9.0%), and ZIKV (4.5%). All IgM-positive individuals were also IgG-positive; overall seroprevalence patterns suggest both endemic transmission and infections occurring at different time points within a previously exposed population. Northern regions showed significantly higher odds of CHIKV IgM (aOR 2.13, 95% CI: 1.18-3.87) and ZIKV IgM (aOR 4.71, 95% CI: 1.53-14.49) seropositivity. Among pregnant women, CHIKV IgM seropositivity was associated with higher odds of preterm birth, while other birth outcome associations should be interpreted cautiously given limited power and the cross-sectional design. PRNT identified samples with predominant virus-specific neutralising patterns, while others showed evidence consistent with multiple flavivirus exposures. Substantial arboviral exposure exists across Nigerian populations, with evidence consistent with ongoing endemic transmission. Dual serology supported by PRNT helped distinguish remote exposure from relatively recent infection, but does not precisely date infection timing. These findings support enhanced surveillance and prospective pregnancy studies incorporating molecular diagnostics (e.g., RT-PCR) to better define the impact of arboviral infection on pregnancy and birth outcomes.

PKR condensation at viral replication complexes initiates its activation.

Dengue virus (DENV), a mosquito-borne RNA virus, poses a significant global health concern due to the lack of effective antivirals and the limitations of current vaccines. To uncover host-targeted vulnerabilities, we performed a functional screen of small-molecule translation modulators. Elongation inhibitors consistently produced the most potent antiviral effects, markedly reducing viral RNA levels, nonstructural protein 3 (NS3) levels, and infectious virus production. Compounds targeting cap-dependent initiation were largely ineffective, except for eIF4E:eIF4G inhibitors, which exerted moderate suppression. This may likely be due to the internal ribosome entry site (IRES)-like activity reported in the DENV 5' untranslated region (UTR). Rocaglamide A strongly suppressed DENV, consistent with an eIF4A helicase-specific vulnerability. Two clinically relevant inhibitors, homoharringtonine (HHT) and bruceantin (BCT), blocked DENV propagation at low nanomolar doses in cell lines and reduced viral RNA and titers in primary human macrophages, underscoring their translational potential. Similar effects were observed with the related Zika virus (ZIKV) in cell lines. These pharmacological data suggest that translation elongation and eIF4A helicase activity are candidate host dependencies for orthoflaviviruses, motivating stage-resolved and in vivo evaluation studies.

Single-entity electrochemistry for Zika Virus titer detection with antiviral peptides modified silver nanoparticles

Zika virus (ZIKV), belonging to the Flaviviridae family, has been a severe threat to human health since the worldwide outbreak. ZIKV is capable of inducing fetal microcephaly, Guillain-Barré syndrome, and other serious neurological complications. Polypyrimidine tract-binding protein 1 (PTBP1) is a key member of the heterogeneous nuclear ribonucleoproteins (hnRNPs) family, functioning in selective mRNA splicing and gene expression regulation. Our previous study has indicated that the expression of PTBP1 increases in astrocytes upon ZIKV infection, yet the precise regulatory mechanisms underlying its role in viral replication remain elusive. In this study, we elucidated the specific pathway by which ZIKV upregulated PTBP1 expression through the activation of hypoxia-inducible factor-1α (HIF-1α) signal. Further investigation revealed that overexpression of PTBP1 effectively inhibited viral replication, whereas knockdown of PTBP1 significantly enhanced viral replication. Mechanistically, using co-immunoprecipitation assays for protein interaction screening, we identified an interaction between PTBP1 and ZIKV non-structural protein NS1. Detailed studies demonstrated that PTBP1 bound and colocalized with NS1 to lead to the degradation of NS1 protein via a lysosomal pathway. Collectively, our findings unveil a novel mechanism underlying that ZIKV infection induces the expression of PTBP1 via the HIF-1α pathway. Subsequently, the accumulated PTBP1 binds to the ZIKV NS1 protein, promoting NS1 degradation and thereby effectively inhibiting viral replication. The study illustrates a distinct restricted cellular factor that regulates ZIKV replication, which provides a potential target for the control of viral replication and pathogenesis during the ZIKV epidemic.IMPORTANCESince the outbreak of ZIKV infection among humans in 2014, a Zika epidemic has caused Zika fever accompanied by fetal microcephaly, Guillain-Barré syndrome, and other neurological symptoms. Emerging evidence reveals that ZIKV infects astrocytes to specifically induce the expression of polypyrimidine tract-binding protein 1 (PTBP1), one of the hnRNP members. However, the interplay between PTBP1 and ZIKV replication is unclear. Here, we uncover a distinct manner that ZIKV induces PTBP1 expression through the activation of hypoxia-inducible factor-1α (HIF-1α) signal. Additionally, activation of the HIF-1α signal hinders ZIKV replication, relying on PTBP1 accumulation. Further investigations suggest that PTBP1 restrains ZIKV replication by interacting with ZIKV NS1 protein, thereby leading to the degradation of NS1 protein via a lysosomal pathway. Collectively, our findings illustrate a novel restricted cellular factor PTBP1 mediated by HIF-1α that regulates ZIKV replication, which provides a potential therapeutic target of viral replication and pathogenesis against the ZIKV pandemic.

New nonacyclic duclauxin derivatives with potent anti-influenza activities from Antarctic fungus Penicillium sp. CPCC 401065.

Effects of candidate vaccines against Zika virus infection: A systematic review of the clinical trials.

Zika virus (ZIKV) vaccine candidates developed through Phase I clinical trials are based on the full-length envelope glycoprotein (E), which presents both desirable and undesirable antigenic determinants. Among the latter, the conserved fusion loop epitope (FLE) within domain II is a major target for flavivirus cross-reactive and poorly neutralizing responses. To eliminate unwanted FLE targeting, we redesigned ZIKV E using a reverse vaccinology approach, excising domain II and allowing domains I and III (DI-DIII) to fold into an independent subunit harboring key neutralizing epitopes. Ifnar1-/- mice vaccinated with ZIKV DI-DIII elicited high ZIKV neutralizing antibodies and were protected from weight loss and death. In addition, sera from DI-DIII vaccinated mice demonstrated a reduced capacity to enhance DENV 1-4 infection in vitro, compared to mice vaccinated with full-length E. This study identifies DI-DIII as a promising immunogen, focusing antibody responses to protective epitopes on ZIKV and minimizing the elicitation of unwanted responses.

The Zika virus (ZIKV) is an Orthoflavivirus linked to several neurological and developmental diseases, and it remains a significant global health concern for which no treatments or vaccines are currently available. In this study, we optimized the malachite green colorimetric assay, previously used to measure the RNA-dependent RNA polymerase (RdRp) activity of the hepatitis C and foot-and-mouth disease viruses, and applied this assay for the preliminary identification of the ZIKV RdRp modulators. RdRp is an enzyme essential for viral replication. Modulator screening was conducted using 204 compounds from the Natural Product Set IV of the National Cancer Institute Developmental Therapeutics Program. We identified two compounds, purpurogallin and digallic acid, as preliminary modulators of the ZIKV RdRp. Future studies will validate these preliminary hits using orthogonal assays, perform dose-response analyses, and elucidate their mechanisms of action.

Computational identification of dual-targeting human miRNAs for Zika virus suppression and host pathway restoration

Zika virus (ZIKV) infection has been inconsistently associated with neurodevelopmental delay (ND). We aimed to compare the incidence of ND between ZIKV-exposed and ZIKV-unexposed children within the ZIKAlliance (ZA) cohort, in Colombia, assessed 2 years after birth (2018-2021). We performed a neurodevelopmental evaluation on normocephalic children (aged 40-72 months) from the ZIKAlliance cohort. Children were classified as ZIKV-exposed (maternal positive RT-qPCR or virus neutralization test - VNT) or unexposed (maternal negative IgG ELISA or VNT in paired antenatal samples). A trained psychologist, blinded to exposure status, administered the Denver Developmental Screening Test II (DDST-II). Children were considered at ND risk if they presented ≥1 delay or ≥2 cautions in one or more areas, within their age range in the DDST-II scale. Inconclusive initial tests were re-evaluated. Adjusted odds ratios were estimated using logistic regression. We analyzed conclusive DDST-II results from 153 children (mean age: 4.7 years; 53.8% male). Overall, 57.2% (n = 83) were classified as cases of ND. Children with ND were more likely to be male (61.4% versus 43.5%) and less likely to attend daycare or school (42.2% versus 11.3%) than children with normal development. After adjusting for child age, sex, household size, and education, the association between in utero ZIKV exposure and ND was not statistically significant (OR = 0.71; 95% CI: 0.32-1.59, p = 0.320). However, children attending daycare or school had a significantly lower risk of ND compared to those who stayed at home. Prenatal ZIKV exposure was not associated with ND in this cohort of normocephalic preschool children. Instead, attending a community daycare or school emerged as a significant protective factor against developmental delays.

Mosquito control remains the cornerstone of the prevention and control of diseases caused by Aedes-borne pathogens, such as dengue, chikungunya and Zika viruses. An innovative vector control method adapted to Aedes albopictus mosquitoes is the Sterile Insect Technique (SIT), which consists of the mass-release of sterilized male mosquitoes. The impact of SIT and the optimization of release strategies can be studied through modelling. The objective of this study was to evaluate the ability of a mathematical model to simulate the impact of SIT releases by comparing the simulation outputs with entomological data collected during and after SIT trials in Mauritius. We modified a model of Ae. albopictus population dynamics (ARBOCARTO) that incorporates variations in temperature and rainfall, as well as the availability of breeding sites to introduce SIT. We then simulated SIT releases under the same conditions as the field trials and assessed the model's ability to realistically reproduce the impact of SIT releases by comparing the simulation outputs with entomological data observed in a trial site (where SIT releases were performed between May 2017 and February 2018) and a control site (without SIT releases). Four simulation scenarios were considered: without SIT, and with SIT applied on 50%, 75% and 100% of the trial area. Results showed that the ARBOCARTO model reproduced the major trends in the intra-annual Ae. albopictus population variations: simulated abundances of eggs, based on weather conditions, were highly and significantly correlated with the egg abundances observed at the SIT control site. The model also matched the trial site data for both the predicted number of newly produced eggs and the percentage of fertile eggs. The simulation results also revealed the importance of the percentage of the area covered by SIT releases as a key parameter for SIT impact, both for the reduction rate and for the resilience time, defined as the time required after the end of releases for the mosquito population to return to its initial state. Thanks to its user-friendly interface, the ARBOCARTO model can be used by vector control services and health stakeholders to simulate the impact of SIT releases and optimize release strategies, taking into account the operational capacity of sterile mosquito rearing facilities and the environmental conditions of the releases.

Zika virus (ZIKV), a mosquito-borne flavivirus that vertically transmits from pregnant women to her fetus, causes microcephaly, a birth defect where newborns show smaller head circumference and brain size compared to normal healthy babies. Microcephalic newborns exhibit several developmental delays and neurological complications. There is no cure or potential therapeutics available to treat ZIKV-caused microcephaly. Human telomerase reverse transcriptase (hTERT)-immortalized mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) have been recently proposed as potential therapeutics in the treatment of various diseases, including cancer, neurological disorders, and viral infections. We hypothesized an important role of hTERT MSC-EVs in providing neuroprotective effects upon ZIKV infection in murine cortical neurons. Our study opens new thoughts on how hTERT-MSC-EV could be proposed as potential therapeutics in ZIKV-caused microcephaly, where they enhance cell viability, inhibit apoptosis, and reduce viral infection and exosome-mediated transmission/dissemination of ZIKV-infected murine cortical neurons in embryonic brains.

Mosquito-borne RNA viruses, including but not limited to the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV), pose serious threats to global public health. Current countermeasure approaches are frequently plagued by insufficient coverage, susceptibility to drug resistance, and poor sustainability. Wolbachia , a natural symbiont within mosquitoes, has been shown to block the replication and transmission of mosquito-borne RNA viruses. In recent years, increasing attention has focused on the mechanism of its antiviral action, which involves the regulation of host lipid metabolism. Here, we systematically reviewed the mechanisms by which mosquito-borne RNA viruses disrupt normal lipid metabolism in host cells, elucidating how these viruses rely on host lipids to achieve invasion and form replication complexes. Multiple pathways of Wolbachia disrupting lipid metabolism are highlighted, including rearranging the host lipid environment, competing with viruses for key metabolic resources, regulating mitochondrial-lipid droplet interactions, and altering membrane fluidity. The translational medicine and public health applications of Wolbachia strains were explored, holding potential for advancing novel antiviral strategies based on metabolic disruption.

The remarkable reported in vitro and in vivo antiviral activity of a commercial, naturally derived, isoquercitrin sample (IQC90) against Ebola (EBOV), Zika virus (ZIKV), and SARS-CoV-2 could not be confirmed with a greater purity isoquercitrin (IQC). To resolve this discrepancy, IQC90 was subjected to a two-step, quantitative bioassay-guided fractionation employing countercurrent separation and gel filtration monitored by inhibition of syncytium formation in HEK293 cells transfected with SARS-CoV-2 spike protein and ACE2. This process revealed the IQC90 antiviral activity to be due to a new family of 21-hydroxyoleanane-3-O-oligosaccharides, named dicitriosides, present at <1 mol %, rather than IQC. The two dominant dicitriosides, the hexoside, dicitrioside A1 (1), and the pentoside, dicitrioside B1 (2), inhibited syncytia formation with an IC50 = 0.530 μM; 25-fold more active than IQC90 (IC50 = 12.8 μM). Beyond anti-SARS-CoV-2 activity, dicitrioside B1 (2) also prevented EBOV infection of Vero E6 cells, supporting the conclusion that the dicitriosides inherit the promising potential of IQC90 as antiviral leads for clinical translation. Ultrahigh field 1.1 GHz NMR spectroscopy, particularly 1D selective TOCSY experiments and nuclear genotyping via quantum-mechanical spin analysis, enabled structure elucidation and provided definitive reference points for the dicitriosides as complex oligoglycoside esters.

We examined previous studies to describe growth deviations in children with Congenital Zika virus Syndrome (CZS), and to determine the factors associated with malnutrition. Protocol of systematic review registered on the PROSPERO platform under code CRD42023460505. The searches were conducted in SciELO, LILACS, Embase, Scopus, and PubMed/MEDLINE databases, as well as in dissertation and thesis repositories. The eligibility criteria required that the publications must be observational, cross-sectional, cohort, or case-control studies conducted with children with microcephaly associated with CZS, which presented results (z-score) of anthropometric indices of weight-for-age, height-for-age, weight-for-height, and/or body mass index (BMI)-for-age; written in English, Portuguese, or Spanish; and published between 2010 and 2023. The z-score values ​​from anthropometric indices and the factors associated with malnutrition (wasting, underweight, overweight, or stunting) were extracted. Eleven studies met our inclusion criteria. In these studies, children's ages ranged from 0 to 48 months. Malnutrition was identified as stunting (14.3% to 57.1%), underweight (14.3% to 54.4%), wasting (4.3% to 48.0%), and, to a lesser extent, as overweight (4.6% to 68.6%). The association of these indices was examined in relation to dysphagia, absence or duration of breastfeeding, delayed introduction of complementary feeding, consumption of ultra-processed foods, and feeding route. It was possible to identify short stature, wasting, excess weight, and inappropriate eating practices in children with CZS.

During the last twenty years, Chikungunya virus (CHIKV), an arthropod-borne alphavirus, has resurged globally and emerged as an important public health concern. Driven by viral adaptive mutations, rapid urbanization, climate change, and the global expansion of Aedes mosquito habitats, CHIKV has continuously expanded its geographic distribution and triggered recurrent outbreaks across multiple continents. In this review, we comprehensively synthesize recent progress in virology, epidemiology, vector biology, diagnostic innovations, and vaccine research, emphasizing the integrated mechanisms that support its continued worldwide spread. Available data suggest that variation in vector competence, viral evolutionary adaptations (e.g., the E1-A226V mutation), and climatic-ecological shifts are key determinants of CHIKV transmission dynamics. Despite the approval of two vaccines, questions persist concerning their long-term safety profile, sustained immunogenicity, economic viability, and fair access in low-resource regions. Furthermore, substantial clinical overlap with dengue and Zika virus infections poses challenges to accurate diagnosis and epidemiological surveillance. It is essential to reinforce genomic and comprehensive vector surveillance and to develop cross-disciplinary risk prediction platforms within a "One Health" framework to improve global preparedness and response capacity. The establishment of data-informed, cooperative prevention strategies remains crucial for reducing the worldwide burden of CHIKV and other comparable arboviral diseases.

Kinetics of neutralizing and binding antibody responses following Zika virus infection during pregnancy: A nested analysis of participants from the microcephaly epidemic research group (MERG) and Zika in infants and pregnancy (ZIP) cohorts.