Papers by preeti vishwakarma
SARS-CoV-2 variants acquire mutations to survive within the host and evade immunity. In addition ... more SARS-CoV-2 variants acquire mutations to survive within the host and evade immunity. In addition to harboring D614G mutation in spike domain, P681R/H mutation at the junction of the S1/S2 furin cleavage site, is found to be the key mutation in variants of concerns (VoC); Alpha, Delta, and Omicron (B.1.1.519). The impact of these acquired mutations on entry, transmissibility, and infectivity of SARS-CoV2 VoC is not clearly identified. Here, using the spike-based pseudovirus, Delta and D614G+P681R synthetic mutants showed a significant increase in the pseudovirus entry, fusion, and infectivity. In contrast, Omicron spike-based pseudovirus and a synthetic P681H mutant showed preferential hACE2-mediated virus entry over TMPRSS2, less fusion, and highly susceptible to Cathepsin L inhibitor. Taken together, these results indicate while the Delta variant utilizes both ACE2 and TMPRSS2 mediated entry, thus causing systemic infection; Omicron has favored growth in ACE2 expressed cells thus m...
Meta Gene, 2018
Background Several gene polymorphisms have been associated with type 2 diabetes mellitus (T2DM) i... more Background Several gene polymorphisms have been associated with type 2 diabetes mellitus (T2DM) in different ethnic groups. Cholesteryl ester transferyl proteins (CETP) promote efflux of excess cholesterol from peripheral tissues back to liver for excretion. Low (Paraoxonase 1) PON1 and (High density lipoprotein) HDL level might decrease its protection and results in T2DM. Based on this, we tried to investigate the Cholesteryl ester transferyl protein gene polymorphism in association with T2DM and lipid traits. Methods In the present case-control study, 300 type 2 diabetes mellitus patients and 300 healthy volunteer were recruited. The CETP (G277A) genotypes were determined by RFLP-PCR, human serum PON1 level was measured by ELISA kit and biochemical analysis was done using standard protocol. Results The frequencies of B1B1, B1B2 and B2B2 genotypes 24%, 62%, 14% and 22%, 60%, 18% were observed in control and T2DM respectively, B2 allele was found higher in type 2 diabetes mellitus, ...
Microbes and Infection, 2021
COVID-19 pandemic has caused severe disruption of global health and devastated the socio-economic... more COVID-19 pandemic has caused severe disruption of global health and devastated the socio-economic conditions all over the world. The disease is caused by SARS-CoV-2 virus that belongs to the family of Coronaviruses which are known to cause a wide spectrum of diseases both in humans and animals. One of the characteristic features of the SARS-CoV-2 virus is the high reproductive rate (R0) that results in high transmissibility of the virus among humans. Vaccines are the best option to prevent and control this disease. Though, the traditional intramuscular (IM) route of vaccine administration is one of the effective methods for induction of antibody response, a needle-free self-administrative intradermal (ID) immunization will be easier for SARS-CoV-2 infection containment, as vaccine administration method will limit human contacts. Here, we have assessed the humoral and cellular responses of a RBD-based peptide immunogen when administered intradermally in BALB/c mice and side-by-side c...
Frontiers in Immunology, 2021
The newly emerged novel coronavirus, SARS-CoV-2, the causative agent of COVID-19 has proven to be... more The newly emerged novel coronavirus, SARS-CoV-2, the causative agent of COVID-19 has proven to be a threat to the human race globally, thus, vaccine development against SARS-CoV-2 is an unmet need driving mass vaccination efforts. The receptor binding domain of the spike protein of this coronavirus has multiple neutralizing epitopes and is associated with viral entry. Here we have designed and characterized the SARS-CoV-2 spike protein fragment 330-526 as receptor binding domain 330-526 (RBD330-526) with two native glycosylation sites (N331 and N343); as a potential subunit vaccine candidate. We initially characterized RBD330-526 biochemically and investigated its thermal stability, humoral and T cell immune response of various RBD protein formulations (with or without adjuvant) to evaluate the inherent immunogenicity and immunomodulatory effect. Our result showed that the purified RBD immunogen is stable up to 72 h, without any apparent loss in affinity or specificity of interactio...
International Immunopharmacology, 2021
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in Engli... more Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre -including this research content -immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Journal of Biological Chemistry, 2021
Sweety Samal, Tripti Shrivastava, Praveen Sonkusre, Zaigham Abbas Rizvi, Rajesh Kumar, Shubbir Ah... more Sweety Samal, Tripti Shrivastava, Praveen Sonkusre, Zaigham Abbas Rizvi, Rajesh Kumar, Shubbir Ahmed, Preeti Vishwakarma, Naveen Yadav, Manish Bansal, Kanchana Chauhan, Sebanta Pokhrel, Supratik Das, Padmakar Tambare, and Amit Awasthi In the present article, it was stated in the Results section that: “All the proteins transiently expressed either in HEK293T or Expi293FTM cells as described in experimental procedures except for M13xΔtGCN4 construct. No expression was seen for M1-3xΔtGCN4 (the experiment was repeated three times).” Both instances of “M13xΔtGCN4” should read “M2-3xΔtGCN4.” Additionally in the article it was stated in the Experimental procedures section that: “The synthetic gene was constructed by linking two peptide sequences originating from the human influenza consensus sequence SLLTEVETPTRSEWESRSSDSSD (Peptide-1) and SLLTEVETPIRNEWGSRSNGSSD (Peptide-2).” It should read: “The synthetic gene was constructed by linking two or three peptide sequences originating from the human influenza consensus sequence SLLTEVETPTRSEWESRSSDSSD (Peptide-1), SLLTEVETPIRNEWGSR SNGSSD (Peptide-2) and SLLTEVETPTRSEWESRSSGSSD-(Peptide-3) linked with GG linker, C terminally tGCN4 as described previously.” The sentence “the third construct consists of one repeat of peptide 1 and two repeats of the peptide 2 and other domains similar toM1-2x.” should read “the third constructM2-3x consists of one repeat of peptide 1, one repeat of the peptide 2, one repeat of peptide 3 and other domains similar to M1-2x as shown in supporting information.” Also, it was stated in the Experimental procedures section that: “Immunization was carried out three times (1, 14, and 28 days).” It should read: “Immunization was carried out three times (0, 21, and 42 days).”
Vaccine, 2019
CD11c+CD8α+ and CD11c+CD11b+ dendritic cells are two major subsets of murine splenic CD11c+ DCs w... more CD11c+CD8α+ and CD11c+CD11b+ dendritic cells are two major subsets of murine splenic CD11c+ DCs which play a crucial role in T cell priming and shaping Th1/Th2 responses, but their role in the context of experimental visceral leishmaniasis (VL) is poorly understood. Herein, we showed that L. donovani infection in Balb/c mice preferentially decreased the population abundance of CD11c+CD11b+ DCs and increased relative abundance of splenic CD11c+CD8α +DCs. During infection, splenic CD11c+CD11b+ DCs induced Th1 differentiation whereas CD11c+CD8α+ DCs promoted Th2 differentiation. Additionally, treatment of infected mice with miltefosine as experimental control exhibited host defense allowing the restoration of CD11c+CD11b+ population and decrease in CD11c+CD8α+ subset. Furthermore, reciprocal regulation of immune accessory surface molecules, Sema4A and OX40L critically determined Th1/Th2 response induced by these DC subsets during VL. L. donovani infection significantly induced OX40L expression and slightly downregulated SEMA 4A expression in CD11c+CD8α+ DCs whereas miltefosine treatment significantly downregulated OX40L expression along with pronounced upregulation of SEMA 4A expression in CD11c+CD11b+ DCs. SiRNA mediated knockdown of SEMA 4A markedly reduced CD11c+CD11b+ driven IFN-γ, TNF-α and IL-12 synthesis in miltefosine treated mice whereas functional blocking of OX40L decreased CD11c+CD8α+ induced IL-10, IL-4 and TGF-β synthesis in L. donovani infected group. Vaccination of Balb/c mice with antigen-pulsed + CpG-ODN-activated DC subsets revealed that only antigen-pulsed CD11c+CD11b+ DCs eliminated parasite load in visceral organ and restored protective Th1 cytokine response. Collectively, our results suggest that differential regulation of splenic CD11c+ subsets by L. donovani is essential for disease progression and specific subtypes may be exploited as prophylactic measures against visceral leishmaniasis.
Parasitology research, 2018
We earlier found that F6 fraction of human filaria Brugia malayi cross-reacted with sera of Leish... more We earlier found that F6 fraction of human filaria Brugia malayi cross-reacted with sera of Leishmania donovani infected hamsters and immunization with F6 inhibited both filarial and leishmanial infections. In the present study, we identified a 52.9-93.6 kDa fraction (Ld1) of L. donovani that cross-reacted with sera of B. malayi infected animals and investigated effect of Ld1 on filarial infection. Immunization of BALB/c mice with Ld1 facilitated B. malayi infection with remarkable increase in parasite burden. Facilitation of filarial infection was associated with downregulated cell proliferation, IL-5, IL-13, IFN-γ, TNF-α, and IL-2 levels and upregulated IL-4 and TGF-β. Ld1 exposure also suppressed MHC class-I, MHC class-II, and FcεR1 expression, and phagocytosis in naive mouse macrophages, and CD4+, CD8+, and CD19+ cell population in mouse spleen. Two-dimensional electrophoresis and matrix-assisted laser desorption ionization-time of flight-mass spectrometry revealed eight protein...
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 2018
IL-1R/TLR signaling plays a significant role in sensing harmful foreign pathogens and mounting ef... more IL-1R/TLR signaling plays a significant role in sensing harmful foreign pathogens and mounting effective innate and adaptive immune responses. However, the precise mechanism by which an obligate intramacrophagic pathogen, breaches IL-1R/TLR signaling and host-protective immunity remains obscure. In this study, we report the novel biphasic role of Toll-interacting protein (Tollip), a negative regulator of the IL-1R/TLR pathway, in the disease progression of experimental visceral leishmaniasis. We observed that during early hours of infection, induced phosphorylation of IRAK-1, resulting in the release of Tollip from the IL-1R-associated kinase (IRAK)-1 complex in J774 macrophages, which then acted as an endocytic adaptor on cell surface IL-1R1 and promoted its lysosomal degradation. In the later stage, Tollip shuttled back to IRAK-1, thereby inhibiting IRAK-1 phosphorylation in association with IRAK-M to neutralize downstream TLR signaling in infected macrophages. Moreover, during la...
Diabetes & metabolic syndrome, Jan 22, 2018
To evaluate the serum paraoxonase 1 activity and determine its association with duration in type ... more To evaluate the serum paraoxonase 1 activity and determine its association with duration in type 2 Diabetes mellitus patients. A total of 80 cases from type 2 diabetes mellitus and healthy controls were enrolled in the present case control study. Human serum PON1 concentration was measured by ELISA and western blotting and it activity was determined spectrophotometrically using 4-nitrophenyle acetate. Diagnostic accuracy of serum PON1 to identify type 2 Diabetes mellitus was calculated with ROC analysis. Serum concentration of LDL, VLDL, TG, A1C, FBS and TC levels showed significantly higher levels in type 2 diabetes patients as compared to healthy controls, however there were no significant differences found in the level of HDL. Serum PON1 concentration and activity monitored in patients with >1 year diabetes showed higher level (75.1 ± 6.8 ng/mL) as compared to patients with >3 years diabetes (65.24 ± 1.6 ng/mL), its level was further decreased in patients with >5 (53.8 ±...
Cellular and Molecular Life Sciences, 2017
In an endeavor to search for affordable and safer therapeutics against debilitating visceral leis... more In an endeavor to search for affordable and safer therapeutics against debilitating visceral leishmaniasis, we examined antileishmanial potential of ammonium trichloro [1,2-ethanediolato-O,O']-tellurate (AS101); a tellurium based non toxic immunomodulator. AS101 showed significant in vitro efficacy against both Leishmania donovani promastigotes and amastigotes at sub-micromolar concentrations. AS101 could also completely eliminate organ parasite load from L. donovani infected Balb/c mice along with significant efficacy against infected hamsters (˃93% inhibition). Analyzing mechanistic details revealed that the double edged AS101 could directly induce apoptosis in promastigotes along with indirectly activating host by reversing T-cell anergy to protective Th1 mode, increased ROS generation and anti-leishmanial IgG production. AS101 could inhibit IL-10/STAT3 pathway in L. donovani infected macrophages via blocking α4β7 integrin dependent PI3K/Akt signaling and activate host MAPKs and NF-κB for Th1 response. In silico docking and biochemical assays revealed AS101's affinity to form thiol bond with cysteine residues of trypanothione reductase in Leishmania promastigotes leading to its inactivation and inducing ROS-mediated apoptosis of the parasite via increased Ca2+ level, loss of ATP and mitochondrial membrane potential along with metacaspase activation. Our findings provide the first evidence for the mechanism of action of AS101 with excellent safety profile and suggest its promising therapeutic potential against experimental visceral leishmaniasis.
Acta tropica, Aug 26, 2017
Journal of Medicinal Chemistry, 2017
Journal of molecular medicine (Berlin, Germany), Jun 1, 2016
15-Deoxy-delta (12,14)-prostaglandin J2 (15d-PgJ2) is a potent bioactive lipid mediator, known to... more 15-Deoxy-delta (12,14)-prostaglandin J2 (15d-PgJ2) is a potent bioactive lipid mediator, known to possess several roles in cell regulation and differentiation along with antimicrobial efficacy against different bacterial and viral infections. In the present study, we investigated the therapeutic efficacy and mechanism of action of 15d-PgJ2 in vitro in Leishmania donovani promastigotes and infected J774 macrophages, and in vivo in Balb/c mice/golden hamster model of experimental visceral leishmaniasis. 15d-PgJ2 effectively killed L. donovani promastigotes and amastigotes in vitro with IC50 of 104.6 and 80.09 nM, respectively. At 2 mg/kg (mice) and 4 mg/kg (hamster) doses, 15d-PgJ2 decreased >90 % spleen and liver parasite burden. It significantly reduced interleukin (IL)-10 and transforming growth factor (TGF)-β synthesis in infected macrophages and splenocytes. 15d-PgJ2 induced reactive oxygen species (ROS)-dependent apoptosis of promastigotes by triggering phosphatidyl serine ex...
A novel, efficient one-pot method has been developed to synthesize amphiphiles such as N-alkylate... more A novel, efficient one-pot method has been developed to synthesize amphiphiles such as N-alkylated and N-alkenylated triethylamines and pyridinium salts for the first time in good yields from n-alcohols and naturally occurring terpenes1 with allylalcohols skeleton, which have industrial application as surfactants,2 DNA carriers3 and other biological applications. The anti-leishmanial activity of N-alkenylated and N-alkylated triethylamine and pyridinium salts was studied and activity results of these compounds will be presented.
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Papers by preeti vishwakarma