Chikungunya virus (CHIKV), causes massive outbreaks of chikungunya infection in several regions of Asia, Africa and Central/South America. Being positive sense RNA virus, CHIKV replication within the host resulting in its genome mutation and led to difficulties in creation of vaccine, drugs and treatment strategies. Vector control strategy has been a gold standard to combat spreading of CHIKV infection, but to eradicate a species from the face of earth is not an easy task. Therefore, alongside vector control, there is a dire need to prevent the infection through vaccine as well as through antiviral strategies. This study was designed to find out conserved B cell and T cell epitopes of CHIKV structural proteins through immuno-informatics and computational approaches, which may play an important role in evoking the immune responses against CHIKV. Several conserved cytotoxic T-lymphocyte epitopes, linear and conformational B cell epitopes were predicted for CHIKV structural polyprotein and their antigenicity was calculated. Among B-cell epitopes “PPFGAGRPGQFGDI” showed a high antigenicity score and it may be highly immunogenic. In case of T cell epitopes, MHC class I peptides ‘TAECKDKNL’ and MHC class II peptides ‘VRYKCNCGG’ were found extremely antigenic. The study led to the discovery of various epitopes, conserved among various strains belonging to different countries. The potential antigenic epitopes can be successfully utilized in designing novel vaccines for combating and eradication of CHIKV disease.

Odorant binding proteins play a key role in the olfactory system and are involved in the odor perception and discrimination of insects. To investigate the potential physiological functions of SaveOBP9 in Sitobion avenae, fluorescence ligand binding experiments, molecular docking, RNA interference, and behavioral tests were performed. Fluorescence binding assay results showed that SaveOBP9 had broad and high (Ki < 10 μM) binding abilities with most of the wheat volatiles, but was more obvious at pH 7.4 than pH 5.0. The binding sites of SaveOBP9 to the volatiles were predicted well by three-dimensional docking structure modeling and molecular docking. Moreover, S. avenae showed a strong behavioral response with the four compounds of wheat. The reduction in mRNA transcript levels after the RNA interference significantly reduced the expression level of SaveOBP9 and induced the non-significant response of S. avenae to the tetradecane, octanal, decanal, and hexadecane. This study provides evidence that SaveOBP9 might be involved in the chemoreception of wheat volatile organic compounds and can successfully contribute in the integrated management programs of S. avenae.

Rift valley fever virus (RVFV) is the causative agent of a viral zoonosis that causes a significant clinical burden in domestic and wild ruminants. Major outbreaks of the virus occur in livestock, and contaminated animal products or arthropod vectors can transmit the virus to humans. The viral RNA-dependent RNA polymerase (RdRp; L protein) of the RVFV is responsible for viral replication and is thus an appealing drug target because no effective and specific vaccine against this virus is available. The current study reported the structural elucidation of the RVFV-L protein by in-depth homology modeling since no crystal structure is available yet. The inhibitory binding modes of known potent L protein inhibitors were analyzed. Based on the results, further molecular docking-based virtual screening of Selleckchem Nucleoside Analogue Library (156 compounds) was performed to find potential new inhibitors against the RVFV L protein. ADME (Absorption, Distribution, Metabolism, and Excretion) and toxicity analysis of these compounds was also performed. Besides, the binding mechanism and stability of identified compounds were confirmed by a 50 ns molecular dynamic (MD) simulation followed by MM/PBSA binding free energy calculations. Homology modeling determined a stable multi-domain structure of L protein. An analysis of known L protein inhibitors, including Monensin, Mycophenolic acid, and Ribavirin, provide insights into the binding mechanism and reveals key residues of the L protein binding pocket. The screening results revealed that the top three compounds, A-317491, Khasianine, and VER155008, exhibited a high affinity at the L protein binding pocket. ADME analysis revealed good pharmacodynamics and pharmacokinetic profiles of these compounds. Furthermore, MD simulation and binding free energy analysis endorsed the binding stability of potential compounds with L protein. In a nutshell, the present study determined potential compounds that may aid in the rational design of novel inhibitors of the RVFV L protein as anti-RVFV drugs.

Vicilin has nutraceutical potential and different noteworthy medicative health-promoting biotic diversions, and it is remarkable against pathogenic microorganisms and insects. In this study, Vigna aconitifolia vicilin (VacV) has been identified and characterized from the seed of Vigna aconitifolia (Jacq.) Marechal (Moth beans). LC-MS/MS analysis of VacV provided seven random fragmented sequences comprising 238 residues, showing significant homology with already reported Vigna radiata vicilin (VraV). VacV was purified using ammonium sulfate precipitation (60%) followed by size exclusion chromatography on Hi-Load 16/60 Superdex 200 pg column and anion-exchange chromatography (Hi trap Q FF column). Purified VacV showed a major ~50 kDa band and multiple lower bands on 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under both reduced and non-reduced conditions. After all, a three-dimensional molecular structure of VacV was predicted, which showed β-sheeted molecular conformation similar to crystallographic structure of VraV. All Vicilins from V. aconitifolia and other plants were divided into six sub-groups by phylogenetic analysis, and VacV shared a high degree of similarity with vicilins of Vigna radiata, Pisum sativum, Lupinus albus, Cicer arietinum and Glycine max. Additionally, VacV (20 μg) has significant growth inhibition against different pathogenic bacteria along strong antifungal activity (50 μg). Likewise, VacV (3.0 mg) produced significant growth reduction in Rice Weevil Sitophilus oryzae larvae after 9 days compared with control. Furthermore, by using MMT assay, the cytotoxicity effect of VacV on the growth of HepG2 liver cancerous cells was tested. VacV showed cytotoxicity against the HepG-2 line and the acquired value was 180 µg after 48 h. Finally, we performed molecular docking against caspase-3 protein (PDB ID: 3DEI) for VacV bioactive receptor interface residues. Hence, our results reveal that VacV, has nutraceutical potential and moth beans can be used as a rich resource of functional foods.

Complex chromosomal rearrangements such as translocations play a critical role in oncogenesis. Translocation detection is vital to decipher their biological role in activating cancer-associated mechanisms. High-throughput chromosomal conformations capture (Hi-C) data have shown promising progress in unveiling the genome variations in a disease condition. Until now, multiple structural data (Hi-C)-based methods are available that can detect translocations in cancer genomes. However, the consistency and specificity of Hi-C-based translocation results still need to be validated with conventional methods. This study used Hi-C data of cancerous cell lines, namely lung cancer (A549), Chronic Myelogenous Leukemia (K562), and Acute Monocytic Leukemia (THP-1), to detect the translocations. The results were cross-validated through whole-genome sequencing (WGS) and paired-read analysis. Moreover, PCR amplification validated the presence of translocated reads in different chromosomes. By integrating different data types, we showed that the results of Hi-C data are as reliable as WGS and can be utilized as an assistive method for detecting translocations in the diseased genome. Our findings support the utility of Hi-C technology to detect the translocations and study their effects on the three-dimensional architecture of the genome in cancer condition.

Aflatoxin B1 (AFB1), a potent mycotoxin, is one of the two primary risk factors that cause liver cancer. In the liver, the bioactivated AFB1 intercalates into the DNA double helix to form a bulky DNA adduct which will lead to mutation if left unrepaired. We have adapted the tXR-seq method to measure the nucleotide excision repair of AFB1-induced DNA adducts. We have found that transcription-coupled repair plays a major role in the damage removal process and the released excision products have a distinctive length distribution pattern. We further analyzed the impact of 3D genome organization on the repair of AFB1-induced DNA adducts. We have revealed that chromosomes close to the nuclear center and A compartments undergo expedited repair processes. Notably, we observed an accelerated repair around both TAD boundaries and loop anchors. These findings provide insights into the complex interplay between repair, transcription, and 3D genome organization, shedding light on the mechanisms underlying AFB1-induced liver cancer. TEASER: Genome-wide mapping repair of AFB1-caused DNA damage by tXR-seq reveals 3D genome organization’s significant impact on the repair.