Biology subjects

Awasthi, A.

Publications and source records attributed to Awasthi, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Dengue Virus Serotype 2 Infection Transcriptionally Reprograms Host Neutrophils to Establish an Immunosuppressive Microenvironment in Mice

Dengue virus (DV) infection triggers profound alterations in host immune responses, yet the transcriptomic reprogramming of innate immune cells during disease progression remains incompletely understood. Here, we demonstrated that Dengue virus serotype 2 (DV-2) infection transcriptionally reprograms host neutrophils, establishing an immunosuppressive microenvironment that facilitates pathogenesis. Through scRNA transcriptomic profiling of bone marrow and spleen cells from the DV-2-infected AG129 mouse model, we delineated a distinct neutrophil signature that shows dynamic shifts in immature and activated populations over the course of dengue infection. We also characterized a specific Ly6Glow subpopulation, notably Fibrinogen-like protein 2 (FGL2)-expressing subsets, that appeared with disease progression. Serum FGL2 levels were significantly elevated in both DV-2-infected mice and human dengue-positive patients. Furthermore, treatment of splenocytes with FGL2 or FGL2-enriched neutrophil secretomes suppressed T cell functional activity and promoted an immunosuppressive phenotype. Together, these findings reveal how DV-2-driven neutrophil reprogramming shapes an immunosuppressive network, highlighting the importance of studying FGL2-expressing neutrophil subsets to understand dengue immunopathogenesis.

immunology↗

bioRxiv2026

Experimental validation of computationally prioritized bisphosphonates reveals no direct in vitro antiviral activity against SARS-CoV-2

It is essential to experimentally evaluate antiviral efficacy predicted by molecular docking and related in silico approaches, which this study achieves for three bisphosphonates (alendronate, minodronate, zoledronate) and treprostinil, identified as potential antiviral therapies in our previous work. These investigational compounds had no detectable cytotoxicity at concentrations up to 25M in Vero E6 cells but also failed to show any antiviral effect against the PQ.8.1 isolate of SARS-CoV-2, when compared to control drugs (ensitrelvir, nirmatrelvir, and remdesivir). It appears that for bisphosphonates, any protective effect is likely due to other virus- or host-mediated mechanisms of action. This study demonstrates the importance of iterating between theoretical hypotheses and experiments to elucidate underlying mechanisms at play.

molecular biology↗

bioRxiv2026

Selective identification of the herb Picrorhiza kurroa and probiotic Lactobacillus fermentum as a synbiotic with fermentation-enhanced physicochemical, biological, and metabolomic properties

PurposeAlthough secondary metabolites of medicinal plants can modulate the gut microbiota, their prebiotic and synbiotic potential is not fully explored. This study aimed to identify novel medicinal plant-probiotic combination(s) that show prebiotic and synbiotic effects through mutual synergism and reciprocal interactions. MethodsTen Himalayan region medicinal plants were screened for their selective prebiotic efficacy by studying in vitro proliferation of three species of lactic acid bacteria (LAB) and concurrent suppression of E. coli. The top-performing plants were evaluated for synergism with LAB through fermentation of pure extracts, followed by physicochemical, biological, and metabolomic profiling. ResultsAmong the ten plant species, Picrorhiza kurroa (PK) and Adhatoda vasica (AV) exhibited promising prebiotic attributes with PAS scores of 0.50 and 0.44, respectively, while Lactobacillus fermentum (LF) emerged as the most compatible probiotic strain. Unlike AV, fermentation of PK with LF demonstrated superior probiotic growth (2.2-fold increase), elevated total flavonoids (21.6% increase), and improved antioxidant capacity (24.02% increase) compared to unfermented PK. Fermented PK significantly enhanced cytoprotective effects and mitigated oxidative (ROS levels/lipid peroxidation) and inflammatory damage (NO/IL-6 levels) in macrophages and muscle cells exposed to separate exogenous stressors (LPS and H2O2). Elemental (ICP-OES) and metabolomic analysis (LC-MS/UHPLC) revealed that LF metabolised major elements of PK (Ca/Fe/K/Na/Cu) and induced biotransformation of large secondary metabolites, including the characteristic iridoid glycosides of PK, into smaller, more abundant metabolites. ConclusionsPK-LF combination is identified as a synbiotic, and its fermented product is a superior bioactive product that can be developed into innovative nutraceuticals or herbal formulations.

biochemistry↗

bioRxiv2025

Molecularly informed analysis of histopathology images using natural language

Histopathology refers to the microscopic examination of diseased tissues and routinely guides treatment decisions for cancer and other diseases. Currently, this analysis focuses on morphological features but rarely considers gene expression information, which can add an important molecular dimension. Here, we introduce SpotWhisperer, an AI method that links histopathological images to spatial gene expression profiles and their text annotations, enabling molecularly grounded histopathology analysis through natural language. Our method outperforms pathology vision-language models on a newly curated benchmark dataset, dedicated to spatially resolved H&E annotation. Integrated into a web interface, SpotWhisperer enables interactive exploration of cell types and disease mechanisms using free-text queries with access to inferred spatial gene expression profiles. In summary, SpotWhisperer analyzes cost-effective pathology images with spatial gene expression and natural-language AI, demonstrating a path for routine integration of microscopic molecular information into histopathology.

bioinformatics↗

bioRxiv2025

Antibody Responses to Salmonella Typhi Antigens among Typhoid Recovered Individuals in an Endemic Region

BackgroundTyphoid fever remains a major public health concern in endemic regions, yet the nature of antibody responses to individual Salmonella Typhi antigens and their potential role in modulating cellular immune functions are not well understood. This gap also applies to the long-term immune response after the vaccination against the disease. ObjectivesTo evaluate the humoral and cellular immune response against the Salmonella Typhi antigens among the Typhoid recovered individuals. MethodsELISA was used to measure antibody responses against five S. Typhi antigens in plasma samples from typhoid-recovered individuals and healthy participants. Vi polysaccharide-specific plasma antibodies were tested for their ability to activate NK cells isolated from healthy donors. Flow cytometry-based assays were performed to analyze T cell and B cell profiles in the peripheral circulation of these individuals. ResultsPolysaccharide antigens mounted better IgA responses among typhoid-recovered individuals compared with healthy participants. Anti-S. Typhi IgM was significantly elevated in the typhoid group for all five antigens (p<0.05), while no significant differences were observed in IgG responses. NK cell activation assays showed comparable levels of activation markers of the NK cells isolated from healthy individuals and treated with the plasma of Typhoid recovered individuals. Analysis of B cell subsets revealed largely comparable distributions between the two groups; however, transitional B cells were elevated among the Typhoid recovered individuals. HlyE-specific memory B cells were detectable in both the groups. CD4 T cell subsets were similar between typhoid-recovered and healthy individuals, whereas differences were observed in CD8 T cell populations, with higher TEMRA cells among recovered individuals and relatively higher central memory CD8 T cells in healthy participants. ConclusionPolysaccharide antigens elicited significantly better IgA response in recovered typhoid participants, possibly reflecting mucosal immune priming from the gut. Persistent IgM antibodies after recovery suggest durable IgM responses following typhoid infection. Similar IgG levels between groups and the presence of antigen-specific memory cells in healthy individuals highlight the influence of repeated exposure in endemic settings. Elevated transitional B cells suggest the reinforcement of the B cells to the peripheral circulation during the disease which remained in the circulation of these individuals. However, elevated TEMRA population of the CD8 T cells has been observed in several other infectious diseases including this study. These findings demonstrate the complexity of humoral and cellular immune responses to S. Typhi in endemic regions.

immunology↗

bioRxiv2025

Circulating Biomarkers for Therapeutic Response to Immune Checkpoint Inhibitor Therapy in Patients with Advanced Lung Cancer

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in the treatment of advanced lung cancer (ALC), but not all patients benefit. To identify responders, patient selection, categorization, and the identification of specific predictive biomarkers are crucial. Our research aims to identify circulating metabolites that could be used to stratify patients into potential responders prior to the initiation of ICIs and to monitor clinical response in real-time during treatment. In the discovery phase, plasma samples (n = 25) from ALC patients receiving ICIs were analyzed using unbiased metabolomics and validated in a distinct patient cohort (n = 39). Five potential biomarkers were identified (FC > 1.5, p 0.05, AUC 0.81-1), including Thiourea and a combined metabolite panel (CMP) consisting of sphingosine-1-phosphate, gentisic acid, glutathione, and 4-hydroxybutanone. Early on-treatment high plasma levels of Thiourea were significantly associated with 5-year progression-free survival [Hazard ratio (HR) = 0.038, 95% confidence interval (CI) = 0.013-0.107, p<0.001] and overall survival [HR = 0.048, 95% CI = 0.019-0.120, p<0.001]. Low levels of CMP early on treatment were significantly associated with progression-free survival [HR = 8.119, 95% CI: 3.767-17.501, p<0.001] and overall survival [HR = 7.367, 95% CI: 3.517-15.433, 3.517-15.433, p<0.001]. This predictive plasma metabolite panel could serve as promising circulating biomarkers for predicting the therapeutic response of ICIs in ALC patients.

cancer biology↗

bioRxiv2025

Cytokine profiling identifies circulating IL-2, IL23 and sPD-L1 as prognostic biomarkers for treatment outcomes in Non-Small cell Lung Cancer patients undergoing anti-PD1 therapy

BackgroundThis study investigates the predictive potential of circulating cytokines for response and survival outcomes in patients with advanced non-small cell lung cancer (NSCLC) undergoing immune checkpoint inhibitor (ICI) therapy. Materials and MethodsA cohort of 64 patients with advanced NSCLC receiving ICI therapy were included. Baseline serum samples were collected prior to ICI initiation and profiled using a multiplex cytokine panel. Logistic regression, Cox regression, and Kaplan-Meier survival analysis were employed to assess associations between cytokine levels, therapeutic response, progression-free survival (PFS), and overall survival (OS). Gene expression levels of key cytokines were validated in peripheral blood mononuclear cells (PBMCs) using quantitative real-time PCR. ResultsElevated baseline levels of IL-2, IL-23, and sPD-L1 were significantly associated with clinical response to ICI therapy. Among these, sPD-L1 emerged as an independent predictor of response (AUC = 0.87). Multivariate Cox regression showed IL-2 (HR = 0.67), sPD-L1 (HR = 0.15), and IL-23 (HR = 1.18) were significantly associated with PFS and also predictive of OS. Notably, combined profiling of IL-2 and sPD-L1 enhanced predictive power (AUC = 0.95 for both PFS and OS). RT-PCR analysis of PBMCs corroborated these findings, confirming upregulation of IL-2 in responders and elevated IL-23 expression in non-responders. ConclusionBaseline cytokine profiling particularly of IL-2, sPD-L1, and IL-23 provides important prognostic and predictive information in advanced NSCLC patients undergoing ICI therapy. These biomarkers may facilitate more personalized approaches to immunotherapy and guide clinical decision-making.

cancer biology↗

bioRxiv2023

Non-canonical NF-κB signaling in dendritic cells promotes intestinal inflammation by restraining the tolerogenic β-catenin-Raldh2 axis

Dendritic cell (DC) dysfunctions exacerbate intestinal pathologies. However, the mechanisms compromising DC-mediated immune controls remain unclear. We found that intestinal DCs from mice subjected to experimental colitis possessed heightened non-canonical NF-{kappa}B signaling, which activates the RelB:p52 heterodimer. Genetic inactivation of this pathway in DCs alleviated inflammation in colitogenic mice. Unexpectedly, RelB:p52 deficiency diminished the transcription of Axin1, a critical component of the {beta}-catenin destruction complex. This reinforced {beta}-catenin-driven expression of Raldh2, which imparts tolerogenic DC attributes by promoting retinoic acid (RA) synthesis. Indeed, DC-specific non-canonical NF-{kappa}B impairment improved the colonic frequency of Tregs and IgA+ B cells, which fostered luminal IgA and eubiosis. Introducing {beta}-catenin haploinsufficiency in non-canonical NF-{kappa}B-deficient DCs moderated Raldh2 activity, reinstating colitogenic sensitivity in mice. Finally, IBD patients displayed a deleterious non-canonical NF-{kappa}B signature in intestinal DCs. In sum, we establish a DC network that integrates non-canonical NF-{kappa}B signaling to subvert RA metabolic pathway in fueling intestinal inflammation. Significance (100)Distorted dendritic cell (DC) functions have been implicated in aberrant intestinal inflammation; however, the underlying mechanism remains obscure. We discovered that the non-canonical NF-{kappa}B pathway exacerbates inflammation in the colitogenic gut by downmodulating {beta}-catenin-driven synthesis of Raldh2 in DCs. Raldh2 represents a key enzyme involved in the production of tolerogenic retinoic acid in intestinal DCs. Beyond regulating immune genes, therefore, non-canonical NF-{kappa}B signaling appears to instruct retinoic acid-mediated control of gut health. While we illustrate a DC network integrating immune signaling and micronutrient metabolic pathways in the intestine, our finding may have broad relevance for nutritional interventions in inflammatory ailments. eToCDeka and Kumar et al. illustrate a DC-circuitry that exacerbates intestinal inflammation in IBD patients and colitogenic mice. Non-canonical NF-{kappa}B signaling restrains {beta}-catenin in DCs to downmodulate Raldh2, which promotes tolerogenic RA synthesis, leading to diminished Treg and IgA+ cell frequencies in the gut. HighlightsO_LIAberrant intestinal inflammation is associated with and exacerbated by non-canonical NF-{kappa}B signaling in DCs. C_LIO_LINon-canonical signaling restrains the tolerogenic {beta}-catenin-Raldh2 axis in DCs by upregulating Axin1. C_LIO_LIDC-specific RelB:p52 impairment promotes {beta}-catenin-dependent Treg accumulation in the gut. C_LIO_LIA DC defect of non-canonical signaling causes {beta}-catenin-dependent increase in luminal sIgA, fostering the gut microbiome. C_LI One sentenceThe non-canonical NF-{kappa}B pathway fuels intestinal inflammation by waning the tolerogenic {beta}-catenin-Raldh2-retinoic acid axis in DCs.

immunology↗

bioRxiv2023

VapC12 ribonuclease toxin modulates host immune response during Mycobacterium tuberculosis infection

Mechanistic understanding of antibiotic persistence is a prerequisite in controlling the emergence of MDR cases in Tuberculosis (TB). We have reported that the cholesterol-induced activation of VapC12 ribonuclease is critical for disease persistence in TB. In this study, we observed that relative to the wild type, mice infected with {Delta}vapC12 induced a proinflammatory response, had a higher pathogen load, and responded better to the anti-TB treatment. In a high-dose infection model, all the mice infected with {Delta}vapC12 succumbed early to the disease. Finally, we reported that the above phenotype of {Delta}vapC12 was dependent on the presence of the TLR4 receptor. Overall, the data suggest that the inability of {Delta}vapC12 to resolve neutrophil-mediated inflammation reduced bacterial killing by altering the T-cell response. In conclusion, our findings suggest the role of the VapC12 toxin in modulating the hosts innate immune response in ways that favor the long-term survival of the pathogen inside the host.

microbiology↗

bioRxiv2023

A shift in the mechanisms controlling hippocampal engram formation during brain maturation

The ability to form precise, episodic memories develops with age, with young children only able to form gist-like memories that lack precision. The cellular and molecular events in the developing hippocampus that underlie the emergence of precise, episodic-like memory formation are unclear. In mice, the absence of a competitive neuronal engram allocation process in the immature hippocampus precluded the formation of sparse engrams and precise memories until the fourth postnatal week, when inhibitory circuits in the hippocampus mature. This age-dependent shift in precision of episodic-like memories involved the functional maturation of parvalbumin-expressing interneurons in subfield CA1 by extracellular perineuronal nets which is necessary and sufficient for the onset of competitive neuronal allocation, sparse engram formation, and memory precision. One-Sentence SummaryEpisodic-like memory precision requires maturation of hippocampal inhibitory interneurons by the extracellular matrix.

neuroscience↗

bioRxiv2022

Anti-COVID-19 Activity of FDA Approved Drugs through RNA G-quadruplex Binding

The COVID-19 pandemic caused by SARS-CoV-2 has caused millions of infections and deaths worldwide. Limited treatment options and the threat from emerging variants underline the need for novel and widely accessible therapeutics. G-quadruplexes (G4s) are nucleic acid secondary structures known to affect many cellular processes including viral replication and transcription. We identified heretofore not reported G4s with remarkably low mutation frequency across >5 million SARS-CoV-2 genomes. The G4 structure was targeted using FDA-approved drugs that can bind G4s - Chlorpromazine (CPZ) and Prochlorperazine (PCZ). We found significant inhibition in lung pathology and lung viral load of SARS-CoV-2 challenged hamsters when treated with CPZ, PCZ that was comparable to the widely used antiviral drug Remdesivir. In support, in vitro G4 binding, inhibition of reverse transcription from RNA isolated from COVID-infected humans, and attenuated viral replication and infectivity in Vero cell cultures were clear in case of both CPZ/PCZ. Apart from the wide accessibility of CPZ/PCZ, targeting relatively invariant nucleic acid structures poses an attractive strategy against fast mutating viruses like SARS-CoV-2.

molecular biology↗

bioRxiv2022

Prophylactic treatment of Glycyrrhiza glabra mitigates COVID-19 pathology through inhibition of pro-inflammatory cytokines in the hamster model and NETosis.

Severe coronavirus disease (COVID-19) is accompanied with acute respiratory distress syndrome & pulmonary pathology, and is presented mostly with inflammatory cytokine release, dysregulated immune response, skewed neutrophil/ lymphocyte ratio, and hypercoagulable state. Though vaccinations have proved effective in reducing the COVID-19 related mortality, the limitation of use of vaccine against immunocompromised, comorbidity, and emerging variants remains a concern. In the current study we investigate for the first-time the efficacy of Glycyrrhiza glabra (GG) extract, a potent immunomodulator, against SARS-CoV-2 infection in hamsters. Prophylactic treatment with GG showed protection against loss in body weight and 35-40% decrease in lung viral load along with reduced lung pathology in the hamster model. Remarkably, GG reduced the mRNA expression of pro-inflammatory cytokines and Plasminogen activator inhibito-1 (PAI-1). In-vitro, GG acted as potent immunomodulator by reducing Th2 and Th17 differentiation and IL-4 and IL-17A cytokine production. In addition, GG also showed robust potential to suppress ROS, mtROS and NETs generation in a concentration dependent manner in both human polymorphonuclear neutrophils (PMNs) and murine bone marrow derived neutrophils (BMDNs). Taken together, we provide evidence for the protective efficacy of GG against COVID-19 and its putative mechanistic insight, which might be developed as a future immunomodulatory approach against various pathologies with high cytokine production, aberrant neutrophil activation including coronavirus infection.

immunology↗

bioRxiv2022

SARS-CoV-2 and its variants, but not Omicron, induces thymic atrophy and impaired T cell development

Pathogenic infections cause thymic atrophy, perturb thymic-T cell development and alter immunological response. Previous studies reported dysregulated T cell function and lymphopenia in coronavirus disease-19 (COVID-19) patients. However, immune-pathological changes, in the thymus, post severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have not been elucidated. Here, we report SARS-CoV-2 infects thymocytes, depletes CD4+CD8+ (double positive; DP) T cell population associated with an increased apoptosis of thymocytes, which leads to severe thymic atrophy in K18-hACE2-Tg mice. CD44+CD25-T cells were found to be enriched in infected thymus, indicating an early arrest in the T cell developmental pathway. Further, Interferon gamma (IFN-{gamma}) was crucial for thymic atrophy, as anti-IFN-{gamma} antibody neutralization rescued the loss of thymic involution. Therapeutic use of remdesivir (prototype anti-viral drug) was also able to rescue thymic atrophy. While Omicron variant of SARS-CoV2 caused marginal thymic atrophy, delta variant of SARS-CoV-2 exhibited most profound thymic atrophy characterized by severely depleted DP T cells. Recently characterized broadly SARS-CoV-2 neutralizing monoclonal antibody P4A2 was able to rescue thymic atrophy and restore thymic developmental pathway of T cells. Together, we provide the first report of SARS-CoV-2 associated thymic atrophy resulting from impaired T cell developmental pathway and also explains dysregulated T cell function in COVID-19.

immunology↗

bioRxiv2022

Innate immune response and distinct metabolomic signatures together drive and shape the SARS-CoV-2-specific T cell response during COVID-19

The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell responses during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0-3, 7-9, and 14-16 days post-COVID-19 positivity) from young mildly symptomatic active COVID-19 patients infected during the first wave in mid-2020. We observed that anti-RBD IgG and viral neutralization are significantly reduced against the Delta variant compared to the ancestral strain. In contrast, compared to the ancestral strain, T cell responses remain preserved against the delta and omicron variants. We determined innate immune responses during the early stage of active infection in response to TLR 3/7/8 mediated activation in PBMCs and serum metabolomic profiling. Correlation analysis indicated PBMCs-derived proinflammatory cytokines, IL-18, IL-1{beta}, and IL-23, and the abundance of plasma metabolites involved in arginine biosynthesis were predictive of a robust SARS-CoV-2-specific Th1 response at a later stage (two weeks after PCR positivity). These observations may contribute to designing effective vaccines and adjuvants that promote innate immune responses and metabolites to induce long-lasting anti-SARS-CoV-2 specific T cells response.

immunology↗

bioRxiv2021

A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 delta variant

Although efficacious vaccines have significantly reduced the morbidity and mortality due to COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can potentially fill. This unmet need is exacerbated by the emergence and spread of SARS-CoV-2 variants of concern (VOCs) that have shown some resistance to vaccine responses. Here we report the isolation of two highly potently neutralizing mAbs (THSC20.HVTR04 and THSC20.HVTR26) from an Indian convalescent donor, that neutralize SARS-CoV-2 VOCs at picomolar concentrations including the delta variant (B.1.617.2). These two mAbs target non-overlapping epitopes on the receptor-binding domain (RBD) of the spike protein thereby preventing the virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Furthermore, the mAb cocktail demonstrated protection against the Delta variant at low antibody doses when passively administered in the K18 hACE2 transgenic mice model, highlighting their potential as cocktail for prophylactic and therapeutic applications. Developing the capacity to rapidly discover and develop mAbs effective against highly transmissible pathogens like coronaviruses at a local level, especially in a low- and middle-income country (LMIC) such as India, will enable prompt responses to future pandemics as an important component of global pandemic preparedness. HighlightsO_LIIdentification of an Indian convalescent donor prior to emergence of SARS-CoV-2 Delta variant whose plasma demonstrated neutralization breadth across SARS-CoV-2 variants of concern (VOCs). C_LIO_LITwo (THSC20.HVTR04 and THSC20.HVTR26) monoclonal antibodies isolated from peripheral memory B cells potently neutralize SARS-CoV-2 VOCs: Alpha, Beta, Gamma, Delta and VOIs: Kappa and Delta Plus. C_LIO_LITHSC20.HVTR04 and THSC20.HVTR26 target non-competing epitopes on the receptor binding domain (RBD) and represent distinct germline lineages. C_LIO_LIPassive transfer of THSC20.HVTR04 and THSC20.HVTR26 mAbs demonstrated protection against Delta virus challenge in K18-hACE2 mice at low antibody doses. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/474152v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1f1b55corg.highwire.dtl.DTLVardef@1b9b438org.highwire.dtl.DTLVardef@e6d2a6org.highwire.dtl.DTLVardef@f92cd_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2021

Effect of prophylactic use of intra-nasal oil formulations in the hamster model of Covid-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection initiates with viral entry in upper respiratory tract leading to coronavirus disease 2019 (Covid-19). Severe Covid-19 is characterized by pulmonary pathologies associated with respiratory failure. Thus, therapeutics aimed at inhibiting entry of the virus or its internalization in the upper respiratory tract, are of interest. Herein, we report the prophylactic application of two intra-nasal formulations provided by the National Medicinal Plant Board (NMPB), Anu oil and Til tailya in SARS-CoV2 infection hamster model. Prophylactic nasal instillation of these oil formulations exhibited reduced viral load in lungs, and resulted in reduced body weight loss and pneumonitis. In line with reduced viral load, histopathlogical analysis revealed a reduction in lung pathology in Anu oil group as compared to the control infected group. However, Til tailya group did not show a significant reduction in lung pathology. Furthermore, molecular analysis using mRNA expression profiling indicated reduced expression of pro-inflammatory cytokines genes, including Th1 and Th17 cytokines for both the intra-nasal formulations as a result of decreased viral load. Together, the prophylactic intra-nasal application of Annu oil seems to be useful in limiting both the viral load and disease severity disease in SARS-CoV2 infection in hamster model.

microbiology↗

bioRxiv2021

Immunological and cardio-vascular pathologies associated with SARS-CoV-2 infection in golden syrian hamster

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in golden Syrian hamster (GSH) causes lung pathology and resembles human coronavirus disease (Covid-19). However, extra-pulmonary pathologies of SARS-CoV-2 infection that result in long Covid remains undefined in GSH. Here, using in silico modelling we show that hamster angiotensin-converting enzyme-2 (ACE-2) and neuropilin-1 (NRP-1) interaction with SARS-CoV-2 is similar to human. Intranasal SARS-CoV-2 infection in GSH resulted in early onset of lung pathologies marked by aggressive inflammatory response. Remarkably, late phase of SARS-CoV2 infection in GSH showed cardiovascular complications (CVC) characterized by ventricular hypertrophy, ventricular wall thickening, interstitial coronary fibrosis and altered lipidomics with elevated cholesterol, low-density lipoprotein and long chain fatty acid triglycerides. Moreover, serum metabolomics profile of infected GSH correlated with Covid19 patients. Together, we propose GSH as a suitable animal model to study immediate and long Covid19 pathologies that could be extended to therapeutics against Covid19 related CVC.

microbiology↗

bioRxiv2020

Evaluation of Safety and Immunogenicity of an Adjuvanted, TH-1 Skewed, Whole Virion Inactivated SARS-CoV-2 Vaccine - BBV152

We report the development and evaluation of safety and immunogenicity of a whole virion inactivated SARS-COV-2 vaccine (BBV152), adjuvanted with aluminium hydroxide gel (Algel), or a novel TLR7/8 agonist adsorbed Algel. We used a well-characterized SARS-CoV-2 strain and an established vero cell platform to produce large-scale GMP grade highly purified inactivated antigen, BBV152. Product development and manufacturing were carried out in a BSL-3 facility. Immunogenicity was determined at two antigen concentrations (3g and 6g), with two different adjuvants, in mice, rats, and rabbits. Our results show that BBV152 vaccine formulations generated significantly high antigen-binding and neutralizing antibody titers, at both concentrations, in all three species with excellent safety profiles. The inactivated vaccine formulation containing TLR7/8 agonist adjuvant-induced Th1 biased antibody responses with elevated IgG2a/IgG1 ratio and increased levels of SARS-CoV-2 specific IFN-{gamma}+ CD4 T lymphocyte response. Our results support further development for Phase I/II clinical trials in humans.

immunology↗