Biology subjects

Ghorai, U.

Publications and source records attributed to Ghorai, U..

4 recordsLinked to original sources

bioRxiv2026

Evidence of residual Brugia malayi infection in TAS-III cleared areas of coastal Odisha: Findings from Molecular Xenomonitoring

BackgroundLymphatic filariasis (LF), caused by Wuchereria (W) bancrofti, Brugia malayi and Brugia (B) timori, remains a major public health problem known for its disfiguring and debilitating effects despite notable progress under the Global Program to Eliminate Lymphatic Filariasis (GPELF). Following recent national directives (2024) restructuring implementation units (IUs) to the block level, all TAS-cleared blocks now require re-evaluation using night blood surveys (NBS) or filarial test strip (FTS) kits. Molecular Xenomonitoring (MX) is recommended as a post-validation surveillance method for detecting active LF transmission in vectors. Therefore, an exploratory study was conducted in two coastal districts of Odisha, namely Jagatsinghpur and Puri, which cleared TAS-III, to investigate the presence of B. malayi and W. bancrofti infections in filaria-transmitting vectors. Methodology/Principal FindingsAdult female mosquitoes were collected from three villages across Jagatsinghpur and Puri districts during March-April 2025. Species were identified morphologically, segregated and pooled. The pooled samples were screened for the presence of filarial DNA using species-specific PCR assays. Of 1,518 collected adult female mosquitoes, 22.6% were Culex quinquefasciatus, 18.3% were Mansonia (Mn) annulifera, and 4.3% were Mansonia uniformis. Among 33 pools screened, six pools were positive for B. malayi DNA (18.18% pool positivity; infection rate 2.88%, 95% CI: 1.23-5.74), in Mn. annulifera, whereas W. bancrofti was not detected. Conclusions/SignificanceThe study provides the first molecular confirmation of B. malayi infection in Mn. annulifera, indicating a persistent Brugian transmission in Odisha even after the implementation of mass drug administration. The Study highlights MX as a sensitive, non-invasive surveillance tool for detecting residual infection in post-MDA and post-TAS settings. The study underscores the need for a standardized MX protocol and integration with entomological monitoring to sustain national LF elimination targets by 2027. Author SummaryLymphatic filariasis is a mosquito-borne disease that can cause severe, disfiguring swelling of the limbs and other lasting disabilities, and it remains a serious public health problem in India. National programmes in India are actively working to eliminate it by giving preventive medicines to communities, conducting surveys to confirm that transmission has ceased, and once an area passes, this treatment is withdrawn. However, it is not always clear whether the parasite has truly disappeared or is still lingering at very low levels. In this study, we searched for the parasite directly inside mosquitoes, an approach that does not require collecting blood from people. We sampled mosquitoes from two coastal districts of Odisha, India, that had already passed the required surveys and stopped treatment. We found the parasite Brugia malayi in Mansonia mosquitoes, the first time this has been shown using this molecular method in the region, although the more common filarial parasite was not detected. Our findings show that transmission can smoulder on even after an area is judged free of disease. Because India has no available rapid field test for this particular parasite, we argue that examining mosquitoes should become a routine safeguard for the countrys elimination effort.

zoology↗

bioRxiv2025

Tretinoin, a Vitamin A derivative, exerts antiviral effects against Chikungunya virus infection through the nuclear retinoid receptor signaling pathways

Chikungunya virus (CHIKV) has reemerged as a global pathogen causing serious public health threat and socio-economic damage, particularly due to the absence of specific antivirals. Retinoids have been reported to exhibit antiviral potentials against multiple viral infections. In the present study, Tretinoin (TR) or all-trans retinoic acid (ATRA) was evaluated for its anti-CHIKV activity using in vitro, in vivo, and ex vivo models. TR was able to impede CHIKV infection efficiently in Vero and physiologically relevant muscle cells, C2C12, with drastic reduction in the viral RNA, proteins and progeny formation. The IC50 of TR against CHIKV was estimated to be 20.05 {micro}M and 19.71 {micro}M in Vero and C2C12 cells, respectively. In addition, the inhibition was effective during entry as well as in the early stages of post CHIKV-infection. Notably, TR showed remarkable virucidal activity. Next, global transcriptome profile demonstrated that the signaling by Retinoic acid pathway was highly upregulated after CHIKV infection and Retinoic acid receptors (RAR), specifically RAR-{beta} are the key mediators for the anti-CHIKV effect of TR. Further, the drug was also capable to modulate CHIKV-induced inflammatory responses by reducing the phosphorylated MAPKs, NF-{kappa}B and proinflammatory cytokines. Interestingly, TR protected C57BL/6 mice from CHIKV challenge by diminishing viral burden leading to reduced clinical scores and better survival. Similar observation was also noticed in the ex vivo model of CHIKV-infected hPBMC-derived monocyte-macrophage populations. In conclusion, this work demonstrated the repurposing potential of TR against CHIKV infection for the first time, encouraging its clinical validation towards future therapeutics. IMPORTANCECHIKV is an arbovirus causing Chikungunya Fever (CHIKF) leading to debilitating arthralgia and myalgia. The unavailability of licensed antivirals or potent vaccines against CHIKV encourages extensive research to find a therapeutic cure. Retinoids, the derivatives of vitamin A, have been repurposed as antiviral agents against a broad range of viruses; however, their efficacy against alphaviruses remains unexplored. Accordingly, Tretinoin (TR), also known as all-trans retinoic acid (ATRA), was validated for anti-CHIKV efficacy in this investigation. Significant perturbation of CHIKV titer through the modulation of Retinoic acid receptors (RAR) was observed upon drug-treatment. Further, TR reduced major inflammatory markers (MAPKs and proinflammatory cytokines) supporting its anti-inflammatory effect. Further, its anti-CHIKV potential was validated in the mouse model and hPBMC-derived monocyte-macrophage cells, indicating the pre-clinical efficacy. Finally, this is the first study to report the anti-CHIKV property of Tretinoin using in vitro, in vivo, and ex vivo approaches suggesting its repurposing potential.

microbiology↗

bioRxiv2025

Chikungunya virus susceptibility increases in the absence of mk2b and mk3 genes in zebrafish model

Chikungunya virus (CHIKV) infection imposes a significant socio-economic burden due to the absence of effective antiviral treatments and vaccines. Host factors are essential for the CHIKV life cycle, making them promising targets for antiviral therapy. Previous studies have identified Mitogen-activated protein kinase activated protein kinase 2 (MK2) and Mitogen-activated protein kinase activated protein kinase 3 (MK3) as key host factors in CHIKV infection; however, their role in an animal model remain unclear. This study highlights the critical roles of MK2 and MK3 host factors in an animal model following CHIKV infection. To investigate their functions, mk2b (mk2b-/-), mk3 (mk3-/-), and mk2b-mk3 (mk2b-/-mk3-/-) double knockout zebrafish were generated using the CRISPR-Cas9 technique. A significant high viral titer of CHIKV was observed in case of all knockout groups compared to the wild-type (WT) control using plaque assay, RT-qPCR and immunofluorescence assay. Among the knockout groups, mk3-/- displayed the highest susceptibility to CHIKV, followed by mk2b-/-. In contrast, the mk2b-/-mk3-/- double knockout exhibited the lowest susceptibility to CHIKV infection. Additionally, severe symptoms such as bent body, impaired response to physical stimuli, and increased mortality were most pronounced in mk3-/- larvae compared to other knockouts and the WT. The expression levels of inf{phi}1 and rsad2 were also elevated in all knockout groups during the early days of infection indicating higher interferon response in the absence of mk2b and mk3 during CHIKV infection. In conclusion, this study confirms that the mk2b and mk3 host proteins are essential in controlling the CHIKV infection in organism level and subsequently may contribute in designing antiviral therapeutics in future. Furthermore, the knockout model of mk2b and mk3 in zebrafish could serve as a valuable tool for studying their roles in other viral infections. Author SummaryCHIKV, transmitted by Aedes aegypti and Aedes albopictus mosquitoes, causes febrile illness and has spread across Africa, Asia, Europe, and America. Despite extensive research, effective antiviral drugs and vaccines are yet to be commercially available. This study examines the role of mk2b and mk3 host factors following CHIKV infection. For this purpose, mk2b and mk3 single as well as double knockout have been generated in zebrafish using the CRISPR-Cas-9 technique. Findings suggest that zebrafish exhibit high CHIKV susceptibility in the absence of mk2b and mk3, confirming its importance during infection. Moreover, these three knockout models could serve as a valuable platform for examine the role of mk2b and mk3 in the presence of other viral infection.

molecular biology↗

bioRxiv2024

Telmisartan impedes JEV infection predominately via AT1/PPARγ axis

Japanese encephalitis, caused by Japanese encephalitis virus (JEV) is a vector born disease for which no specific therapeutics are available yet. Binding of angiotensin II (Ang II) to angiotensin II type 1 (AT1) receptor induces release of inflammatory cytokines associated with viral encephalitis. Accordingly, Ang II receptor blockers (ARBs) have been proposed to manage encephalitis. Since Telmisartan (TM, antagonist of AT1 and agonist of PPAR{gamma}) has relatively better brain access than other ARBs, this investigation aims to evaluate its anti-JEV efficacy in vitro and in vivo. TM reduced JEV titer, RNA and protein (NS3) significantly in the BHK-21 cells with IC50 of 24.68M and CC50 of >350 M (Selectivity Index >14.18) indicating its potential of repurposing against JEV. The anti-JEV efficacy of TM was further observed in macrophages (RAW264.7) and neuronal (SH-SY5Y) cells. Interestingly, the viral load was reduced significantly in pre, co and post-treatment conditions of TM, however most efficiently (80%) in post treatment. In presence of GW (PPAR{gamma} antagonist) and AG (AT1 agonist), viral infection was increased remarkably while AT1 was upregulated and PPAR{gamma} was downregulated. Whereas, TM treatment reversed the levels of AT1 and PPAR{gamma} during infection. Further, reduction of inflammatory markers like p-IRF-3, COX-2 and p-NF-{kappa}B was observed after TM treatment in RAW264.7 cells suggesting its immunomodulation through the AT1/PPAR{gamma} axis. Finally, the anti-JEV potential of TM was validated in mice model through the reduction of disease score, viral protein and histological changes. Thus, the preclinical efficacy of TM suggests its suitability for repurposing against JEV.

microbiology↗