Browsing by Author "Sonal Gupta"

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A combined subunit vaccine comprising BP26, Omp25 and L7/L12 against brucellosis
(Oxford University Press, 2019) Sonal Gupta; Damini Singh; Manish Gupta; Rakesh Bhatnagar
The current vaccines against brucellosis, namely Brucella abortus strains 19 and RB51, prevent infection in animals but pose potential risks like virulence and attenuation reversal. In this milieu, although subunit vaccination using a single potent immunogen of B. abortus, e.g. BP26 or Omp25 or L7/L12 etc., appears as a safer alternative, nonetheless it confers inadequate protection against the zoonosis compared to attenuated vaccines. Hence, we have investigated the prophylactic potential of a combined subunit vaccine (CSV) comprising the BP26, Omp25 and L7/L12 antigens of B. abortus, in mice model. Sera obtained from CSV immunized mice groups showed heightened IgG titers against all the three components and exhibited specificity upon immunoblotting, reiterating their authenticity. Further, the IgG1/IgG2a ratio obtained against each antigen revealed a predominant Th2 immune response in CSV immunized mice group. However, on assessing the levels of Th1-dependent (IFN-γ and TNF-α) and Th2-dependent (IL-4 and IL-10) cytokines in different formulations, prominent IFN-γ levels were elicited in CSV immunized mice. Further, upon infection with virulent B. abortus 544, the combined subunit vaccinated mice displayed superior degree of protection (Log10 reduction) than the individual vaccines; however, B. abortus S19 showed the highest protection. Altogether, this study suggests that co-immunization of three B. abortus immunogens as a CSV complements and triggers a mixed Th1/Th2 immune response leading to superior degree of protection against pathogenic B. abortus 544 infection. © FEMS 2020.
Development of a novel multiepitope chimeric vaccine against anthrax
(Springer Verlag, 2019) Somya Aggarwal; Vikas Kumar Somani; Sonal Gupta; Rajni Garg; Rakesh Bhatnagar
Abstract: Bacillus anthracis (BA), the etiological agent of anthrax, secretes protective antigen (PA), lethal factor (LF), and edema factor (EF) as major virulence mediators. Amongst these, PA-based vaccines are most effective for providing immunity against BA, but their low shelf life limits their usage. Previous studies showed that B-cell epitopes, ID II and ID III present in PA domain IV possess higher toxin neutralization activity and elicit higher antibody titer than ID I. Moreover, N-terminal region of both LF and EF harbors PA-binding sites which share 100% identity with each other. Here, in this study, we have developed an epitope-based chimeric vaccine (ID–LFn) comprising ID II–ID III region of PA and N-terminal region of LF. We have also evaluated its protective efficacy as well as stability and found it to be more stable than PA-based vaccine. Binding reactivities of ID–LFn with anti-PA/LF/EF antibodies were determined by ELISA. The stability of chimeric vaccine was assessed using circular dichroism spectroscopy. ID–LFn response was characterized by toxin neutralization, lymphocyte proliferation isotyping and cytokine profiling. The protective efficacy was analyzed by challenging ID–LFn-immunized mice with B. anthracis (pXO1 + and pXO2 + ). ID–LFn was found to be significantly stable as compared to PA. Anti-ID–LFn antibodies recognized PA, LF as well as EF. The T-cell response and the protective efficacy of ID–LFn were found to be almost similar to PA. ID–LFn exhibits equal protective efficacy in mice and possesses more stability as compared to PA along with the capability of recognizing PA, LF and EF at the same time. Thus, it can be considered as an improved vaccine against anthrax with better shelf life. Graphical abstract: [Figure not available: see fulltext.] ID-LFn, a novel multiepitope chimeric anthrax vaccine: ID-LFn comprises of immunodominant epitopes of domain 4 of PA and N-terminal homologous stretch of LF and EF. The administration of this protein as a vaccine provides protection against anthrax. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential
(BioMed Central, 2019) Sonal Gupta; Juveria Khan; Priti Kumari; Chintam Narayana; R. Ayana; Malabika Chakrabarti; Ram Sagar; Shailja Singh
Background: Malaria is one of the deadliest infectious diseases caused by protozoan parasite of Plasmodium spp. Increasing resistance to anti-malarials has become global threat in control of the disease and demands for novel anti-malarial interventions. Naturally-occurring coumarins, which belong to a class of benzo-α-pyrones, found in higher plants and some essential oils, exhibit therapeutic potential against various diseases. However, their limited uptake and non-specificity has restricted their wide spread use as potential drug candidates. Methods: Two series of carbohydrate fused pyrano[3,2-c]pyranone carbohybrids which were synthesized by combination of 2-C-formyl galactal and 2-C-formyl glucal, with various freshly prepared 4-hydroxycoumarins were screened against Plasmodium falciparum. The anti-malarial activity of these carbohybrids was determined by growth inhibition assay on P. falciparum 3D7 strain using SYBR green based fluorescence assay. Haemolytic activity of carbohybrid 12, which showed maximal anti-malarial activity, was determined by haemocompatibility assay. The uptake of the carbohybrid 12 by parasitized erythrocytes was determined using confocal microscopy. Growth progression assays were performed to determine the stage specific effect of carbohybrid 12 treatment on Pf3D7. In silico studies were conducted to explore the mechanism of action of carbohybrid 12 on parasite microtubule dynamics. These findings were further validated by immunofluorescence assay and drug combination assay. Results: 2-C-formyl galactal fused pyrano[3,2-c]pyranone carbohybrid 12 exhibited maximum growth inhibitory potential against Plasmodium with IC50 value of 5.861 μM and no toxicity on HepG2 cells as well as no haemolysis of erythrocytes. An enhanced uptake of this carbohybrid compound was observed by parasitized erythrocytes as compared to uninfected erythrocytes. Further study revealed that carbohybrid 12 arrests the growth of parasite at trophozoite and schizonts stage during course of progression through asexual blood stages. Mechanistically, it was shown that the carbohybrid 12 binds to α,β-heterodimer of tubulin and affects microtubule dynamics. Conclusion: These findings show carbohydrate group fusion to 4-hydroxycoumarin precursor resulted in pyrano-pyranones derivatives with better solubility, enhanced uptake and improved selectivity. This data confirms that, carbohydrate fused pyrano[3,2-c]pyranones carbohybrids are effective candidates for anti-malarial interventions against P. falciparum. © 2019 The Author(s).
Erratum: Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential (Malaria Journal (2019) 18 (346) DOI: 10.1186/s12936-019-2971-z)
(BioMed Central Ltd., 2020) Sonal Gupta; Juveria Khan; Priti Kumari; Chintam Narayana; R. Ayana; Malabika Chakrabarti; Ram Sagar; Shailja Singh
Please note, following publication of the original article [1], the authors have advised of three errors that are present in the published article. Firstly, the two instances of 'Albumax II' in the 'Methods' section of the article are incorrect: the reagent 'Albumax I' should be referred to instead. Secondly, 'giemsa' (also referred to in the 'Methods' section) should be capitalized, as 'Giemsa'. Finally, an incorrect version of Fig. 4 has been incorporated in the article; please find the correct version of Fig. 4 in this article, for reference. © 2020 The Author(s).
Homology modelling and molecular simulation approach to prediction of B-cell and T-cell epitopes in an OMP25 peptide vaccine against Brucella abortus
(Taylor and Francis Ltd., 2023) Dhananjay Jade; Sonal Gupta; Surender Mohan; Sreenivasan Ponnambalam; Michael Harrison; Rakesh Bhatnagar
The live attenuated vaccine composition against brucellosis poses potential risks to recipient animals. Therefore, we have analysed an in-silico approach to design a novel multi-epitope vaccine peptide to elicit a desirable immune response against Brucella abortus infection. This study designed a peptide vaccine based on outer membrane protein from B. abortus. The selected OMP sequence shows 0.7575 antigenic proteins. We predicted the T-cell epitopes of different lengths. Cluster analysis was performed for 180 epitope peptides, showcasing a total of 19 clusters, constituting 14 clusters as Consensus clusters and 5 as Singleton clusters. We select the top three clusters which has 24 peptides showing antigen property. Selected 24-antigen peptides were docked with MHC classes I and II and selected the top eight peptides based on binding energy used for molecular dynamic simulation. Immuno-informatics analysis, Molecular Docking and Molecular simulation indicated that epitope peptide vaccine could work as effective peptides helpful in scheming peptide vaccine against B. abortus infection by developing broad-spectrum peptide vaccine in near future. The use of Omp25 as a vaccine candidate has been supported based on previous experimental studies. Multitope vaccine can be developed which can protect mice against virulent B. abortus challenge. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
Pathogen induced subversion of NAD+ metabolism mediating host cell death: a target for development of chemotherapeutics
(Springer Nature, 2021) Ayushi Chaurasiya; Swati Garg; Ashish Khanna; Chintam Narayana; Ved Prakash Dwivedi; Nishant Joshi; Zill e Anam; Niharika Singh; Jhalak Singhal; Shikha Kaushik; Amandeep Kaur Kahlon; Pallavi Srivastava; Manisha Marothia; Mukesh Kumar; Santosh Kumar; Geeta Kumari; Akshay Munjal; Sonal Gupta; Preeti Singh; Soumya Pati; Gobardhan Das; Ram Sagar; Anand Ranganathan; Shailja Singh
Hijacking of host metabolic status by a pathogen for its regulated dissemination from the host is prerequisite for the propagation of infection. M. tuberculosis secretes an NAD+-glycohydrolase, TNT, to induce host necroptosis by hydrolyzing Nicotinamide adenine dinucleotide (NAD+). Herein, we expressed TNT in macrophages and erythrocytes; the host cells for M. tuberculosis and the malaria parasite respectively, and found that it reduced the NAD+ levels and thereby induced necroptosis and eryptosis resulting in premature dissemination of pathogen. Targeting TNT in M. tuberculosis or induced eryptosis in malaria parasite interferes with pathogen dissemination and reduction in the propagation of infection. Building upon our discovery that inhibition of pathogen-mediated host NAD+ modulation is a way forward for regulation of infection, we synthesized and screened some novel compounds that showed inhibition of NAD+-glycohydrolase activity and pathogen infection in the nanomolar range. Overall this study highlights the fundamental importance of pathogen-mediated modulation of host NAD+ homeostasis for its infection propagation and novel inhibitors as leads for host-targeted therapeutics. © 2021, The Author(s).
Simultaneous immunization with omp25 and l7/l12 provides protection against brucellosis in mice
(MDPI AG, 2020) Sonal Gupta; Surender Mohan; Vikas Kumar Somani; Somya Aggarwal; Rakesh Bhatnagar
Currently used Brucella vaccines, Brucella abortus strain 19 and RB51, comprises of live attenuated Brucella strains and prevent infection in animals. However, these vaccines pose potential risks to recipient animals such as attenuation reversal and virulence in susceptible hosts on administration. In this context, recombinant subunit vaccines emerge as a safe and competent alternative in combating the disease. In this study, we formulated a divalent recombinant vaccine consisting of Omp25 and L7/L12 of B. abortus and evaluated vaccine potential individually as well as in combination. Sera obtained from divalent vaccine (Omp25+L7/L12) immunized mice group exhibited enhanced IgG titers against both components and indicated specificity upon immunoblotting reiterating its authenticity. Further, the IgG1/IgG2a ratio obtained against each antigen predicted a predominant Th2 immune response in the Omp25+L7/L12 immunized mice group. Upon infection with virulent B. abortus 544, Omp25+L7/L12 infected mice exhibited superior Log10 protection compared to individual vaccines. Consequently, this study recommends that simultaneous immunization of Omp25 and L7/L12 as a divalent vaccine complements and triggers a Th2 mediated immune response in mice competent of providing protection against brucellosis. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Stereoselective synthesis of carbohydrate fused pyrano[3,2-c]pyranones as anticancer agents
(Royal Society of Chemistry, 2018) Priti Kumari; Sonal Gupta; Chintam Narayana; Shakeel Ahmad; Nidhi Vishnoi; Shailja Singh; Ram Sagar
Pyrano[3,2-c]pyranone is an important structural motif present in many natural products exhibiting diverse biological activities. Two series of carbohydrate fused pyrano[3,2-c]pyranone derivatives (n = 20) were efficiently synthesized starting from 2-C-formyl galactal and 2-C-formyl glucal, reacting with various 4-hydroxycoumarins in a very short reaction time (10 min) under microwave assisted conditions. The anticancer activity of these synthesized pyrano[3,2-c]pyranones was determined in detail through cellular assays against MCF-7 (breast), MDA-MB-231 (breast) and HepG2 (liver) cancer cell lines. The newly synthesized pyrano[3,2-c]pyranones were screened for their cell-viability and anti-proliferative activity against MCF-7, MDA-MB-231 and HepG2 cell lines. Compounds 12, 13 and 14 exhibited high growth inhibitory potencies selectively against MCF-7 cells with half-maximal inhibitory concentration (IC50) values of 19.9, 14.5 and 10.9 μM respectively. Compounds 12, 13, 14, 15 and 19 inhibited the growth of MDA-MB-231 cells (breast) by 43, 44, 37, 31 and 45% respectively. However, no inhibitory effect was observed for these compounds in the human liver cancer cell line (HepG2) and normal cell lines (HEK293, human embryonic kidney cells). Mechanistic studies showed that these compounds alter the cell morphology and cause G2/M arrest in MCF-7. Further studies showed that compounds 12, 13 and 14 significantly inhibited cell migration which was accompanied by altered microtubule distribution. An enhanced accumulation of these compounds in cells was observed as compared to the 4-hydroxycoumarins precursor in the intracellular uptake assay. These findings confirm that carbohydrate fused pyrano[3,2-c]pyranones are better candidates for anticancer activity. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
The Omic Insights on Unfolding Saga of COVID-19
(Frontiers Media S.A., 2021) Arvinpreet Kaur; Mehak Chopra; Mahak Bhushan; Sonal Gupta; Hima Kumari P; Narmadhaa Sivagurunathan; Nidhi Shukla; Shalini Rajagopal; Purva Bhalothia; Purnima Sharma; Jalaja Naravula; Renuka Suravajhala; Ayam Gupta; Bilal Ahmed Abbasi; Prittam Goswami; Harpreet Singh; Rahul Narang; Rathnagiri Polavarapu; Krishna Mohan Medicherla; Jayaraman Valadi; Anil Kumar S; Gyaneshwer Chaubey; Keshav K. Singh; Obul Reddy Bandapalli; Polavarapu Bilhan Kavi Kishor; Prashanth Suravajhala
The year 2019 has seen an emergence of the novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease of 2019 (COVID-19). Since the onset of the pandemic, biological and interdisciplinary research is being carried out across the world at a rapid pace to beat the pandemic. There is an increased need to comprehensively understand various aspects of the virus from detection to treatment options including drugs and vaccines for effective global management of the disease. In this review, we summarize the salient findings pertaining to SARS-CoV-2 biology, including symptoms, hosts, epidemiology, SARS-CoV-2 genome, and its emerging variants, viral diagnostics, host-pathogen interactions, alternative antiviral strategies and application of machine learning heuristics and artificial intelligence for effective management of COVID-19 and future pandemics. © Copyright © 2021 Kaur, Chopra, Bhushan, Gupta, Kumari P, Sivagurunathan, Shukla, Rajagopal, Bhalothia, Sharma, Naravula, Suravajhala, Gupta, Abbasi, Goswami, Singh, Narang, Polavarapu, Medicherla, Valadi, Kumar S, Chaubey, Singh, Bandapalli, Kavi Kishor and Suravajhala.