Virander S Chauhan

International Centre for Genetic Engineering and Biotechnology, Trst, Friuli Venezia Giulia, India

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Publications (212)680.7 Total impact

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    ABSTRACT: Amyloid-β aggregation is a major etiological phenomenon in Alzheimer’s disease. Herein, we report peptide-based inhibitors that diminish the amyloid load by obviating Aβ aggregation. Taking the hexapeptide fragment, Aβ32-37 as lead, more than forty new peptides were synthesized. Upon evaluation of the newly synthesized hexapeptides as inhibitors of Aβ toxicity by the MTT-based cell viability assay, a number of peptides exhibited significant Aβ aggregation inhibitory activity at sub-micromolar concentration range. A hexapeptide (1) showed complete mitigation of Aβ toxicity in the cell culture assay at 2 μM. In the ThT fluorescence assay, upon incubation of Aβ with this peptide, we observed no increase in the ThT fluorescence relative to control. The secondary structure estimation by circular dichroism spectroscopy and morphological examination by transmission electron microscopy further confirmed the results.
    No preview · Article · Feb 2016 · ACS Chemical Neuroscience
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    ABSTRACT: Eukaryotic Armadillo (ARM) repeat proteins are multifaceted with prominent roles in cell-cell adhesion, cytoskeletal regulation and intracellular signaling among many others. One such ARM repeat containing protein, ARM Repeats Only (ARO), has recently been demonstrated in both Toxoplasma (TgARO) and Plasmodium (PfARO) parasites to be targeted to the rhoptries during the late asexual stages. TgARO has been implicated to play an important role in rhoptry positioning i.e. directing the rhoptry towards the apical end of the parasite. Here, we report for the first time that PfARO exhibits a DNA binding property and a dynamic sub-cellular localization between the nucleus (early schizont) and rhoptry (late schizont) during the different stages of the asexual blood-stage life cycle. PfARO possesses a putative nuclear export signal (NES) and the nucleo-apical shuttling was sensitive to Leptomycin B (LMB) suggesting that the nuclear export was mediated by CRM1. Importantly, PfARO specifically bound an A-T rich DNA sequence of the P. falciparum Gyrase A (PfgyrA) gene, suggesting that the DNA binding specificity of PfARO is likely due to the AT-richness of the probe. This is a novel functional characteristic that has not been reported previously for any P. falciparum ARM containing protein and suggests a putative role for PfARO in gene regulation. This study describes for the first time a conserved P. falciparum ARM repeat protein with a high degree of functional versatility.
    Full-text · Article · Feb 2016 · PLoS ONE
  • Nidhi Hans · Udbhav Relan · Nneha Dubey · Deepak Gaur · V.S. Chauhan
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    ABSTRACT: Plasmodium falciparum is the causative organism for the most severe form of malaria among humans. The clinical symptoms are accredited to the asexual stage of parasite life cycle, involving merozoite invasion of erythrocyte, development and re-invasion into the new erythrocyte. Interaction of parasite proteins present on the surface or secreted from apical organelles with the host receptors is indispensable for the invasion process. Identification and elucidation of precise localization and function of these proteins will not only enhance our understanding of this process but will also aid in the progress of development of treatment strategies against malaria. Here we report the identification and localization of a novel protein, PfAEP (Plasmodium falciparum Apical Exonemal Protein) (PF3D7_1137200/ PF11_0383) which is conserved across Plasmodium species. Transcription and translation analysis have confirmed its expression in the schizont stage of P. falciparum. Super-resolution microscopy in schizonts and merozoites revealed its localization in the exonemes of P. falciparum.
    No preview · Article · Oct 2015 · Molecular and Biochemical Parasitology

  • No preview · Article · Apr 2015 · Journal of Hepatology
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    ABSTRACT: Search term Clear input Advanced Help Result Filters Display Settings: Abstract Send to: Proc Natl Acad Sci U S A. 2015 Jan 12. pii: 201415466. [Epub ahead of print] Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr is crucial for Plasmodium falciparum erythrocyte invasion. Reddy KS1, Amlabu E1, Pandey AK1, Mitra P1, Chauhan VS1, Gaur D2. Author information 1Malaria Group, International Centre for Genetic Engineering & Biotechnology (ICGEB), New Delhi, India 110067; and. 2Malaria Group, International Centre for Genetic Engineering & Biotechnology (ICGEB), New Delhi, India 110067; and School of Biotechnology, Jawaharlal Nehru University (JNU), New Delhi, India 110067 Abstract Erythrocyte invasion by Plasmodium falciparum merozoites is a highly intricate process in which Plasmodium falciparum reticulocyte binding-like homologous protein 5 (PfRH5) is an indispensable parasite ligand that binds with its erythrocyte receptor, Basigin. PfRH5 is a leading blood-stage vaccine candidate because it exhibits limited polymorphisms and elicits potent strain-transcending parasite neutralizing antibodies. However, the mechanism by which it is anchored to the merozoite surface remains unknown because both PfRH5 and the PfRH5-interacting protein (PfRipr) lack transmembrane domains and GPI anchors. Here we have identified a conserved GPI-linked parasite protein, Cysteine-rich protective antigen (CyRPA) as an interacting partner of PfRH5-PfRipr that tethers the PfRH5/PfRipr/CyRPA multiprotein complex on the merozoite surface. CyRPA was demonstrated to be GPI-linked, localized in the micronemes, and essential for erythrocyte invasion. Specific antibodies against the three proteins successfully detected the intact complex in the parasite and coimmunoprecipitated the three interacting partners. Importantly, full-length CyRPA antibodies displayed potent strain-transcending invasion inhibition, as observed for PfRH5. CyRPA does not bind with erythrocytes, suggesting that its parasite neutralizing antibodies likely block its critical interaction with PfRH5-PfRipr, leading to a blockade of erythrocyte invasion. Further, CyRPA and PfRH5 antibody combinations produced synergistic invasion inhibition, suggesting that simultaneous blockade of the PfRH5-Basigin and PfRH5/PfRipr/CyRPA interactions produced an enhanced inhibitory effect. Our discovery of the critical interactions between PfRH5, PfRipr, and the GPI-anchored CyRPA clearly defines the components of the essential PfRH5 adhesion complex for P. falciparum erythrocyte invasion and offers it as a previously unidentified potent target for antimalarial strategies that could abrogate formation of the crucial multiprotein complex.
    No preview · Article · Jan 2015 · Proceedings of the National Academy of Sciences
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    Pinky Kumari · Dinkar Sahal · Virander S Chauhan
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    ABSTRACT: Plasmodium falciparum (Pf) employs a crucial PfHRPII catalyzed reaction that converts toxic heme into hemozoin. Understanding heme polymerization mechanism is the first step for rational design of new drugs, targeting this pathway. Heme binding and hemozoin formation have been ascribed to PfHRPII aspartate carboxylate-heme metal ionic interactions. To investigate, if this ionic interaction is indeed pivotal, we examined the comparative heme binding and β-hematin forming abilities of a wild type dendrimeric peptide BNT1 {harboring the native sequence motif of PfHRPII (AHHAHHAADA)} versus a mutant dendrimeric peptide BNTM {in which ionic Aspartate residues have been replaced by the neutral Asparaginyl residues (AHHAHHAANA)}. UV and IR data reported here reveal that at pH 5, both BNT1 and BNTM exhibit comparable heme binding as well as β-hematin forming abilities, thus questioning the role of PfHRPII aspartate carboxylate-heme metal ionic interactions in heme binding and β-hematin formation. Based on our data and information in the literature we suggest the possible role of weak dispersive interactions like N-H···π and lone-pair···π in heme binding and hemozoin formation.
    Full-text · Article · Nov 2014 · PLoS ONE
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    ABSTRACT: Background: Malaria and human immunodeficiency virus (HIV) infection during pregnancy affect the transplacental transfer of antibodies against several pathogens from mother to fetus, although the effect of malaria and HIV infection on the transfer of antimalarial antibodies remains unclear. Methods: Levels of total immunoglobulin G (IgG), immunoglobulin M (IgM), and IgG subtypes against the following Plasmodium falciparum antigens were measured in 187 pairs of mother-cord plasma specimens from Mozambique: 19-kDa fragment of merozoite surface protein 1 (MSP119), erythrocyte binding antigen 175 (EBA175), apical membrane antigen 1 (AMA1), and parasite lysate. Placental antibody transfer was defined as the cord-to-mother ratio (CMR) of antibody levels. Results: Maternal malaria was associated with reduced CMR of EBA175 IgG (P = .014) and IgG1 (P = .029), AMA1 IgG (P = .002), lysate IgG1 (P = .001), and MSP1 IgG3 (P = .01). Maternal HIV was associated with reduced CMR of MSP1 IgG1 (P = .022) and IgG3 (P = .023), lysate IgG1 (P = .027) and IgG3 (P = .025), AMA1 IgG1 (P = .001), and EBA175 IgG3 (P = .001). Decreased CMR was not associated with increased adverse pregnancy outcomes or augmented risk of malaria in the infant during the first year of life. Conclusions: Placental transfer of antimalarial antibodies is reduced in pregnant women with malaria and HIV infection. However, this decrease does not contribute to an increased risk of malaria-associated morbidity during infancy.
    Full-text · Article · Sep 2014 · The Journal of Infectious Diseases
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    ABSTRACT: Insulin provides a classical model of a globular protein, yet how the hormone changes conformation to engage its receptor has long been enigmatic. Interest has focused on the C-terminal B-chain segment, critical for protective self-assembly in β cells and receptor binding at target tissues. Insight may be obtained from truncated "microreceptors" that reconstitute the primary hormone-binding site (α-subunit domains L1 and αCT). We demonstrate that, on microreceptor binding, this segment undergoes concerted hinge-like rotation at its B20-B23 β-turn, coupling reorientation of Phe(B24) to a 60° rotation of the B25-B28 β-strand away from the hormone core to lie antiparallel to the receptor's L1-β2 sheet. Opening of this hinge enables conserved nonpolar side chains (Ile(A2), Val(A3), Val(B12), Phe(B24), and Phe(B25)) to engage the receptor. Restraining the hinge by nonstandard mutagenesis preserves native folding but blocks receptor binding, whereas its engineered opening maintains activity at the price of protein instability and nonnative aggregation. Our findings rationalize properties of clinical mutations in the insulin family and provide a previously unidentified foundation for designing therapeutic analogs. We envisage that a switch between free and receptor-bound conformations of insulin evolved as a solution to conflicting structural determinants of biosynthesis and function.
    Full-text · Article · Aug 2014 · Proceedings of the National Academy of Sciences
  • Jiban Jyoti Panda · Virander Singh Chauhan
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    ABSTRACT: Self-assembly of biomolecules facilitates the creation of a diverse range of hierarchical nanostructures from a wide range of polymeric and non-polymeric materials. Peptides and specifically short peptides are very attractive in this respect due to their unmatched biocompatibility, ease of synthesis, functionability as well as tunable bioactivity along with the availability of rich chemistry for fine-tuning the structure and function of peptides according to environmental conditions. Self-assembled peptide based nanostructures such as tubes, filaments, fibrils, hydrogels, vesicles, and monolayers have been studied by many research groups and found application as three-dimensional cell growing scaffolds, dental implants, neural tissue engineering scaffolds and as carriers for drugs, proteins and genes, and nucleotides. Nanostructures are also being developed from designed or modified amino acids to have enhanced cellular as well as in vivo stability. These modified nanostructures showed enhanced drug delivery properties both under in vivo and in vitro conditions.
    No preview · Article · Jul 2014
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    ABSTRACT: A Plasmodium falciparum chimeric protein, PfMSP-Fu24, was constructed by genetically coupling immunodominant, conserved regions of two merozoite surface proteins, the 19-kDa region C-terminal region of merozoite surface protein 1 (PfMSP-119) and an 11-kDa conserved region of merozoite surface protein 3 (PfMSP-311), to augment the immunogenicity potential of these blood-stage malaria vaccine candidates. Here we describe an improved, efficient, and scalable process to produce high-quality PfMSP-Fu24. The chimeric protein was produced in Escherichia coli SHuffle T7 Express lysY cells that express disulfide isomerase DsbC. A two-step purification process comprising metal affinity followed by cation exchange chromatography was developed, and we were able to obtain PfMSP-Fu24 with purity above 99% and with a considerable yield of 23 mg/liter. Immunogenicity of PfMSP-Fu24 formulated with several adjuvants, including Adjuplex, Alhydrogel, Adjuphos, Alhydrogel plus glucopyranosyl lipid adjuvant, aqueous (GLA-AF), Adjuphos+GLA-AF, glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE), and Freund's adjuvant, was evaluated. PfMSP-Fu24 formulated with GLA-SE and Freund's adjuvant in mice and with Alhydrogel and Freund's adjuvant in rabbits produced high titers of PfMSP-119 and PfMSP-311-specific functional antibodies. Some of the adjuvant formulations induced inhibitory antibody responses and inhibited in vitro growth of P. falciparum parasites in the presence as well as in the absence of human monocytes. These results suggest that PfMSP-Fu24 can form a constituent of a multistage malaria vaccine.
    Full-text · Article · Apr 2014 · Clinical and vaccine Immunology: CVI
  • Shaheena Parween · Anurag Misra · Suryanarayanarao Ramakumar · Virander Singh Chauhan
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    ABSTRACT: Peptide based self assembled nanostructures have attracted growing interest in recent years due to their numerous potential applications particularly in biomedical sciences. Di-peptide Phe–Phe was shown previously to self-assemble into nanotube like structures. In this work, we studied the affect of peptide backbone length and conformational flexibility on the self assembly process by using two dipeptides based on the Phe–Phe backbone (βPhe–Phe and βPhe–ΔPhe): one containing a flexible βPhe amino acid, and the other containing both a flexible βPhe as well as a backbone constraining ΔPhe (α,β-dehydrophenylalanine) amino acid. Electron microscopy and X-ray diffraction experiments revealed that these new di-peptides can self-assemble into nanotubes having different properties than the native Phe–Phe nanotubes. These nanotubes were stable over a broad range of temperatures and the introduction of non-natural amino acids provided them with stability against the action of nonspecific proteases. Moreover, these dipeptides showed no cytotoxicity towards HeLa and L929 cells, and were able to encapsulate small drug molecules. We further showed that anticancerous drug mitoxantrone was more efficient in killing HeLa and B6F10 cells when entrapped in nanotubes as compared to free mitoxantrone. Therefore, these β-phenylalanine and α,β-dehydrophenylalanine containing dipeptide nanotubes may be useful in the development of biocompatible and proteolytically stable drug delivery vehicles.
    No preview · Article · Apr 2014
  • Akash Saini · Virander Singh Chauhan
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    ABSTRACT: Two highly fibrillogenic peptide sequences (MNFGAFSINP and EDLIIKGISV) were previously reported in the C-terminal fragment (CTF) of TDP-43 (220-414), a protein recently implicated in neuro-degenerative diseases like ALS and FTLD-U. It was observed that the sequences MNFGAFS and EDLIIKG harbor their respective fibrillogenic domains. Here, the self-assembling properties of peptides obtained by systematic deletion of residues from these two sequences were investigated with the help of light scattering, thioflavin T fluorescence, transmission electron microscopy, and CD spectroscopy. It was found that the pentapeptide, NFGAF, and the tetrapeptide, DLII, are the shortest fibrillogenic sequences from MNFGAFS and EDLIIKG, respectively. Structure function studies revealed that self-assembly of the peptides is largely governed by hydrophobic interactions. Both NFGAF and DLII formed hydrogels based on a complex fibrillar network, at significantly low concentrations, and of remarkable strength and stability. Of particular interest was DLII, a rare aliphatic tetrapeptide which formed a hydrogel at a concentration of 1mg/ml in less than an hour. Interestingly, various other tetrapeptides based on DLII (YLII, KLII, NLII and LIID) also formed hydrogels of comparable physical properties, suggesting that an amphipathic peptide design based on the hydrophobic LII motif and a single residue polar terminus is highly favorable for hydrogelation. Peptides discovered in this study, especially DLII and its variants, are some of the shortest ever reported to show such structural and functional features, suggesting that they can be useful templates for the design of peptide based soft materials.
    No preview · Article · Feb 2014 · Langmuir
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    Maryam Imam · Shailja Singh · Naveen Kumar Kaushik · Virander Singh Chauhan
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    ABSTRACT: Merozoite surface protein 3 of Plasmodium falciparum, a 40 kDa protein that also binds heme, has been biophysically characterized, for its tendency to form highly elongated oligomers. The present study aims to systematically analyse the regions in MSP3 sequence involved in oligomerization and correlate its aggregation tendency with its high affinity for binding with heme. Through SEC, DLS and TEM, we have found that MSP3, previously known to form elongated oligomers, actually forms self-assembled filamentous structures that possess amyloid like characteristics. By expressing different regions of MSP3, we observed that the previously described leucine zipper region at the C-terminus of MSP3 may not be the only structural element responsible for oligomerization, and that other peptide segments like MSP3192-196aa (YILGW) may also be required. MSP3 aggregates on incubation were transformed to long unbranched amyloid fibrils. Using immunostaining methods, we found that 5-15 micron size long fibrillar structures stained by anti-MSP3 Abs, were attached to the merozoite surface and also associated with erythrocyte membrane. We also found MSP3 to bind several molecules of heme by UV-spectrophotometry, HPLC and electrophoresis. Present study suggested that its ability to bind heme is somehow related to its inherent characteristics to form oligomers. Moreover, heme interaction with a surface protein like MSP3, which does not participate in hemozoin formation, may suggest a protective role against the heme released from unprocessed hemoglobin released after schizont egress. These studies point out to other roles that MSP3 may play during the blood stages of the parasite, in addition to be an important vaccine candidate.
    Full-text · Article · Dec 2013 · Journal of Biological Chemistry
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    ABSTRACT: Plasmodium falciparum reticulocyte binding-like homologous protein 5 (PfRH5) is an essential merozoite ligand that binds with its erythrocyte receptor, Basigin. PfRH5 is an attractive malaria vaccine candidate as it is expressed by a wide number of P. falciparum strains, cannot be genetically disrupted and exhibits limited sequence polymorphisms. Viral vector induced PfRH5 antibodies potently inhibited erythrocyte invasion. However, it has been a challenge to generate full-length recombinant PfRH5 in a bacterial cell based expression system. Here, we have produced full-length recombinant PfRH5 in Escherichia coli that exhibits specific erythrocyte binding similar to that of the native PfRH5 parasite protein and also importantly elicits potent invasion inhibitory antibodies against a number of P. falciparum strains. Anti-Basigin antibodies blocked the erythrocyte binding of both native and recombinant PfRH5 further confirming that they bind with Basigin. We have thus successfully produced full-length PfRH5 as a functionally active erythrocyte binding recombinant protein with a conformational integrity that mimics the native parasite protein and elicits potent strain-transcending parasite neutralizing antibodies. P. falciparum has the capability to develop immune escape mechanisms and thus blood-stage malaria vaccines that target multiple antigens or pathways may prove to be highly efficacious. In this regard, antibody combinations targeting PfRH5 and other key merozoite antigens produced potent additive inhibition against multiple worldwide P. falciparum strains. PfRH5 was immunogenic when immunized with other antigens eliciting potent invasion inhibitory antibody responses with no immune interference. Our results strongly support the development of PfRH5 as a component of a combination blood-stage malaria vaccine.
    Full-text · Article · Oct 2013 · Infection and Immunity
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    ABSTRACT: Subtilisin-like proteases of malaria parasite Plasmodium falciparum (PfSUB1, 2 and 3) are expressed at late asexual blood stages. PfSUB1 and 2 are considered important drug targets due to their essentiality for parasite blood stages and role in merozoite egress and invasion of erythrocytes. We have earlier shown the in vitro serine protease activity of PfSUB3 and its localization at asexual blood stages. In this study, we attempted to identify the biological substrate(s) of PfSUB3 and found parasite profilin (PfPRF) as a substrate of PfSUB3. Eukaryotic profilins are multifunctional proteins with primary role in regulation of actin filament assembly. PfPRF possesses biochemical features of eukaryotic profilins and its rodent ortholog is essential in blood stages. Profilin from related apicomplexan parasite Toxoplasma gondii (TgPRF) is known to be involved in parasite motility, host cell invasion, active egress from host cell, immune evasion and virulence in mice. In this study, mature PfSUB3 proteolysed recombinant PfPRF in a dose-dependent manner in in vitro assays. Recombinant PfPRF was assessed for its proinflammatory activity and found to induce high level of TNF-α and low but significant level of IL-12 from mouse bone marrow-derived dendritic cells. Proteolysis of PfPRF by PfSUB3 is suggestive of the probable role of the protease in the processes of motility, virulence and immune evasion.
    Full-text · Article · Sep 2013 · Molecular and Biochemical Parasitology
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    ABSTRACT: Current standard of care for sustained back of the eye drug delivery is surgical placement or injection of large, slow release implants using a relatively large 22 gauge needle. We designed novel dipeptide (phenylalanine-α,β-dehydrophenylalanine; Phe-∆Phe) based nanotubes with a diameter of ~15-30nm and a length of ~1500nm that could be injected with a 33 gauge needle for sustained intravitreal delivery of pazopanib, a multi-targeted tyrosine kinase inhibitor. The drug could be loaded during nanotube assembly or post-loaded after nanotube formation, with the former being more efficient at 25% w/w pazopanib loading and ~55% loading efficiency. Plain and peptide loaded nanotubes were non-cytotoxic to retinal pigment epithelial cells even at a concentration of 200μg/ml. Following intravitreal injection of fluorescently labeled nanotubes using a 33 gauge needle in a rat model, the nanotubes persistence and drug delivery were monitored using noninvasive fluorophotometry, electron microscopy and mass spectrometry analysis, respectively. Nanotubes persisted in the vitreous humor during the 15days study and pazopanib levels in the vitreous humor, retina, and choroid-RPE at the end of the study were 4.5, 5, and 2.5-fold higher compared to the plain drug. Thus, Phe-∆Phe nanotubes allow intravitreal injections with a small gauge needle and sustain drug delivery.
    No preview · Article · Sep 2013 · Journal of Controlled Release
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    Nidhi Hans · Shailja Singh · Alok K Pandey · K Sony Reddy · Deepak Gaur · Virander S Chauhan
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    ABSTRACT: Malaria remains a major health problem worldwide. All clinical symptoms of malaria are attributed to the asexual blood stages of the parasite life cycle. Proteins resident in apical organelles and present on the surface of P. falciparum merozoites are considered promising candidates for the development of blood stage malaria vaccines. In the present study, we have identified and characterized a microneme associated antigen, PfMA [PlasmoDB Gene ID: PF3D7_0316000, PFC0700c]. The gene was selected by applying a set of screening criteria such as transcriptional upregulation at late schizogony, inter-species conservation and the presence of signal sequence or transmembrane domains. The gene sequence of PfMA was found to be conserved amongst various Plasmodium species. We experimentally demonstrated that the transcript for PfMA was expressed only in the late blood stages of parasite consistent with a putative role in erythrocyte invasion. PfMA was localized by immunofluorescence and immuno-electron microscopy to be in the micronemes, an apical organelle of merozoites. The functional role of the PfMA protein in erythrocyte invasion was identified as a parasite adhesin involved in direct attachment with the target erythrocyte. PfMA was demonstrated to bind erythrocytes in a sialic acid independent, chymotrypsin and trypsin resistant manner and its antibodies inhibited P. falciparum erythrocyte invasion. Invasion of erythrocytes is a complex multistep process that involves a number of redundant ligand-receptor interactions many of which still remain unknown and even uncharacterized. Our work has identified and characterized a novel P. falciparum adhesin involved in erythrocyte invasion.
    Full-text · Article · Sep 2013 · PLoS ONE
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    Nirmalya Bag · Ashraf Ali · Virander Singh Chauhan · Thorsten Wohland · Aseem Mishra
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    ABSTRACT: Monomeric hIAPP significantly destabilizes both model and live cell membranes by increasing membrane fluidity. This interaction with membranes happens via carpet formation followed by lipid extraction in a concentration dependent manner and thus we propose that hIAPP aggregation prior to membrane interaction may not be necessary for its cytotoxicity.
    Full-text · Article · Aug 2013 · Chemical Communications
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    ABSTRACT: Three de novo designed low molecular weight cationic peptides (IJ2, IJ3 and IJ4) containing an unnatural amino acid α, β - didehydrophenylalanine (∆Phe), exhibited potent antifungal activity against fluconazole (FLC) sensitive and resistant clinical isolates of Candida albicans as well as non-albicans, other yeast and filamentous pathogenic fungi. In present study, their synthesis, susceptibility of different fungi and the mechanism of anti-candidal action have been elucidated. The antimicrobial peptides (AMPs) were synthesized by solid-phase method and checked for antifungal activity against different yeasts and fungi by broth microdilution method. Anti-candidal mode of action of the peptides was investigated through detecting membrane permeabilization by confocal microscopy, reactive oxygen species (ROS) generation by fluorometry, apoptosis and necrosis by flow cytometry and cell wall damage using scanning and transmission electron microscopy. The MIC of the peptides against C. albicans, other yeast and filamentous fungal pathogens ranged between 3.91-250μM. All three peptides exhibited effect on multiple targets in C. albicans including disruption of cell wall structures, compromised cell membrane permeability leading to their enhanced entry into the cells, accumulation of ROS and induction of apoptosis. The peptides also showed synergistic effect when used in combination with fluconazole (FLC) and caspofungin (CAS) against C. albicans. The study suggests that the AMPs alone or in combination with conventional antifungals hold promise for the control of fungal pathogens, and need to be further explored for treatment of fungal infections.
    Full-text · Article · Jul 2013 · Biochimica et Biophysica Acta
  • Shaheena Parween · Ashraf Ali · Virander Singh Chauhan
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    ABSTRACT: Peptide based capping agents for gold nanoparticles (GNPs) are possible alternatives for capping and derivatizing GNPs, but suffer from a major disadvantage of sensitivity towards non specific proteases, which may limit their in-vivo utility. Using non-natural analogs of natural α-amino acids offer an attractive alternate strategy to circumvent this potential bottleneck in realizing full potential of peptide based capping gents for GNPs for biological applications. Here, we have designed and developed pentapeptides containing non-natural amino acid (α, β-dehydrophenylalanine and α-aminoisobutyric acid) as capping agents for GNPs. All these peptides were able to efficiently cap GNPs and peptide induced aggregation was not observed. Peptide capped GNPs showed minimal cytotoxicity to mammalian cell lines (HeLa and L929) as well as mice spleenocytes. They encapsulated small drug like molecules and peptide capped GNPs entrapping drugs were more efficient in killing HeLa cells compared to the free drug. Therefore, these non-natural amino acid containing peptide capped GNPs may be further developed as alternate drug delivery vehicles.
    No preview · Article · Jun 2013 · ACS Applied Materials & Interfaces

Publication Stats

4k Citations
680.70 Total Impact Points


  • 1990-2015
    • International Centre for Genetic Engineering and Biotechnology
      • • Plant Biology: Plant Transformation Research Group
      • • Plant Biology: Plant Molecular Biology Research Group
      Trst, Friuli Venezia Giulia, India
  • 2011
    • Jawaharlal Nehru University
      New Dilli, NCT, India
  • 1986-2011
    • University of Delhi
      • • Department of Chemistry (Faculty of Science)
      • • Department of Zoology (Faculty of Science)
      Old Delhi, NCT, India
  • 2010
    • Fakir Mohan University
      Bāleshwar, Odisha, India
  • 2009
    • Jamia Hamdard University
      New Dilli, NCT, India
    • Indian Institute of Science
      • Molecular Biophysics Unit
      Bengalūru, Karnataka, India
  • 1998
    • Indian Council of Medical Research
      New Dilli, NCT, India
  • 1992
    • National Center for Genetic Engineering and Biotechnology (BIOTEC)
      Bang Kadi, Pathum Thani, Thailand