Biology subjects

Parn, S.

Publications and source records attributed to Parn, S..

3 recordsLinked to original sources

bioRxiv2023

Carbonic anhydrase is a novel diagnostic biomarker for the detection of the parasitic trematode Schistosoma mansoni in the intermediate snail host, Biomphalaria glabrata

Schistosomiasis is a major public health concern worldwide. Although praziquantel is currently available as the only treatment option for schistosomiasis, the absence of reliable diagnostic and prognostic tools highlights the need for the identification and characterization of new drug targets. Recently, we identified the B. glabrata homolog (accession number XP_013075832.1) of human CAXIV, showing 37% amino acid sequence identity, from a BLAST search in NCBI (National Center for Biotechnology Information). Carbonic Anhydrases (CAs) are metalloenzymes that catalyze the reversible hydration/dehydration of CO2/HCO3. These enzymes are associated with many physiological processes, and their role in tumorigenesis has been widely implicated. CAs create an acidic extracellular environment that facilitates the survival, metastasis, and growth of cancer cells. In this study, we investigated the role of CA inhibition in B. glabrata snails exposed to S. mansoni miracidia. We analyzed the expression of the B. glabrata CA encoding transcript in juvenile susceptible and resistant snails, with and without exposure to S. mansoni. Our results showed that the expression of the CA mRNA encoding transcript was upregulated during early and prolonged infection in susceptible snails (BBO2), but not in the resistant BS-90 stock. Notably, sodium salicylate, a form of aspirin, inhibited the expression of CA, post-exposure, to the parasite. Increasing research between parasites and cancer has shown that schistosomes and cancer cells share similarities in their capacity to proliferate, survive, and evade host immune mechanisms. Here, we show that this model system is a potential new avenue for understanding the role of CA in the metastasis and proliferation of cancer cells. Further studies are needed to explore the potential of CA as a biomarker for infection in other schistosomiasis-causing parasites, including S. japonicum and S. haematobium.

molecular biology↗

bioRxiv2022

SARS-CoV-2 Omicron (BA.1 and BA.2) specific novel CD8+ and CD4+ T cell epitopes targeting spike protein.

The Omicron (BA.1/B.1.1.529) variant of SARS-CoV-2 harbors an alarming 37 mutations on its spike protein, reducing the efficacy of current COVID-19 vaccines. This study identified CD8+ and CD4+ T cell epitopes from SARS-CoV-2 S protein mutants. To identify the highest quality CD8 and CD4 epitopes from the Omicron variant, we selected epitopes with a high binding affinity towards both MHC I and MHC II molecules and applied other clinical checkpoint predictors including immunogenicity, antigenicity, allergenicity, instability, and toxicity. Subsequently, we found eight Omicron (BA.1/B.1.1.529) specific CD8+ and eleven CD4+ T cell epitopes with a world population coverage of 76.16% and 97.46%, respectively. Additionally, we identified common epitopes across Omicron BA.1 and BA.2 lineages that target mutations critical to SARS-CoV-2 virulence. Further, we identified common epitopes across B.1.1.529 and other circulating SARS-CoV-2 variants, such as B.1.617.2 (Delta). We predicted CD8 epitopes binding affinity to murine MHC alleles to test the vaccine candidates in preclinical models. The CD8 epitopes were further validated using our previously developed software tool PCOptim. We then modeled the three-dimensional structures of our top CD8 epitopes to investigate the binding interaction between peptide-MHC and peptide-MHC-TCR complexes. Importantly, our identified epitopes are targeting the mutations on the RNA-binding domain and the fusion sites of S protein. This could potentially eliminate viral infections and form long-term immune responses compared to rather short-lived mRNA vaccines and maximize the efficacy of vaccine candidates against the current pandemic and potential future variants.

immunology↗

bioRxiv2021

Design of Peptide Vaccine for COVID19: CD8+ and CD4+ T cell epitopes from SARS-CoV-2 open-reading-frame protein variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has challenged public health at an unprecedented scale which has led to a dramatic loss of human life worldwide. To design a protective vaccine against SARS-CoV-2, it is necessary to understand which SARS-CoV-2 specific epitopes can elicit a T cell response and provide protection across a broad population. In this study, PLpro and RdRp, two immunogenic non-structural proteins from an immunodominant gene region ORF1ab, as well as ORF3a and ORF9b are identified as potential vaccine targets against SARS-CoV-2. To select top epitopes for vaccine design, we used various clinical properties, such as antigenicity, allergenicity, toxicity and IFN-y secretion. The analysis of CD8 and CD4 T cell epitopes revealed multiple potential vaccine constructs that cover a high percentage of the world population. We identified 8 immunogenic, antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD8 proteins for nsp3, 4 for nsp12, 11 for ORF3a and 3 for ORF9b that are common across four lineages of variants of concern - B.1.1.7, P.1, B.1.351 and B.1.617.2, which protect 98.12%, 87.08%, 96.07% and 63.8% of the world population, respectively. We also identified variant specific T cell epitopes that could be useful in targeting each variant strain separately. Including the prediction of mouse MHC affinity towards our top CD8 epitopes, our study revealed a total of 3 immunogenic, antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD8 epitopes overlapping with 6 antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD4 epitopes across all four variants of concern which can effectively be utilized in pre-clinical studies. The landscape of SARS-CoV-2 T cell epitopes that we identified can help lead SARS-CoV-2 vaccine development as well as epitope-based peptide vaccine research in the future.

immunology↗