Biology subjects

Thakur, J. K.

Publications and source records attributed to Thakur, J. K..

4 recordsLinked to original sources

bioRxiv2021

Zinc2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro.

Zinc deficiency is linked to poor prognosis in COVID-19 patients while clinical trials with Zinc demonstrate better clinical outcome. The molecular target and mechanistic details of anti-coronaviral activity of Zinc remain obscure. We show that ionic Zinc not only inhibits SARS-CoV-2 main protease (Mpro) with nanomolar affinity, but also viral replication. We present the first crystal structure of Mpro-Zn2+ complex at 1.9 [A] and provide the structural basis of viral replication inhibition. We show that Zn2+ coordinates with the catalytic dyad at the enzyme active site along with two previously unknown water molecules in a tetrahedral geometry to form a stable inhibited Mpro-Zn2+ complex. Further, natural ionophore quercetin increases the anti-viral potency of Zn2+. As the catalytic dyad is highly conserved across SARS-CoV, MERS-CoV and all variants of SARS-CoV-2, Zn2+ mediated inhibition of Mpro may have wider implications.

biochemistry↗

bioRxiv2021

Coordinated overexpression of OsSUT1, OsSWEET11 and OsSWEET14 in rice impairs carbohydrate metabolism that has implications in plant growth, yield and susceptibility to Xanthomonas oryzae pv oryzae (Xoo)

Enhancing carbohydrate export to sink tissues is considered as a feasible approach for improving photosynthetic efficiency and crop yield. In Oryza sativa Sucrose Transporter OsSUT1 located in companion cells and Sugars Will Eventually be Exported Transporters (SWEETs); OsSWEET11 and OsSWEET14 present in phloem parenchyma mesophyll cell plasma membranes are involved in long distance sucrose transport. OsSWEET11 and OsSWEET14 also play important role in host-pathogen interaction of rice plants and Xanthomonas oryzae pv oryzae (Xoo) that causes bacterial leaf blight. Three genes, OsSUT1, OsSWEET11, and OsSWEET14 were overexpressed under the control of their native promoters in rice to modulate long distance sugar transport and disease resistance. The transgenics displayed several phenotypic aberrations such as reduced plant height and seed weight due to altered sucrose transport and metabolism. Lower sucrose transport rate in transgenics than the WT resulted in reduced sucrose, fructose and glucose and increased starch accumulation in their leaves at the end of dark period. Transcriptional analysis revealed a reduction in the expression of genes involved in sucrose synthesis pathway in transgenics. Normal growth and development of transgenic seedlings were restored in growth media supplemented with 3% sucrose demonstrating in planta sucrose limitation. Remarkably, transgenic lines had diminished susceptibility to Xoo than the WTs due to low sugar content in the leaves demonstrating that rice plants maintain an optimum level of SWEETs for proper plant growth and development, and upregulation of these SWEETs in rice mimicks Xoo attack impelling plants to reduce sugar content in the apoplasm to inhibit pathogen growth.

plant biology↗

bioRxiv2019

Designing of a mini-core that effectively represents 3004 diverse accessions of rice

Genetic diversity provides foundation for plant breeding and genetic research. As part of the 3K Rice Genome Project, over 3000 rice genomes were recently sequenced. We added four Indian rice accessions to it and made original panel of 3004 accessions. However, large set of germplasms are difficult to preserve and evaluate. Construction of core and mini-core collections is an efficient method for managing genetic resources. This study aims to designing of mini-core comprised of 520 accessions representing original panel. The designed mini-core captured most of the SNPs and represented all phenotypes and geographical regions. The mini-core was validated using different statistical analyses and had representation from all major groups including japonica, indica, aus/boro and aromatic/basmati. GWAS analyses with mini-core panel efficiently reproduced the marker-traits association identified among original 3004 panel. Expression analysis of trait-associated genes highlights the relevance of such mini-core panel. Haplotype analysis could also validate our mini-core panel. Apart from mini-core, we identified few regional and varietal specific marker-trait associations which were not evident in original panel. In this era of large-scale sequencing projects, such a strategy of designing mini-core will be very useful.\n\nOne-sentence summaryDesigning of mini-core as manageable association panel that efficiently mirroring the large and diverse collection of 3004 rice accessions.

plant biology↗

bioRxiv2019

Genome-wide analysis of polymorphisms identified domestication-associated polymorphism desert carrying important rice grain size/weight QTL

Rice grain size and weight are major determinant of grain quality and yield and so have been under rigorous selection since domestication. However, genetic basis for contrasting grain size/weight trait among indian germplasm, and their association with domestication shaped evolutionary region is not studied before. To identify genetic basis of grain size/weight two long (LGG) and two short grain genotypes (SGG) were resequenced. LGG (LGR and Pusa Basmati 1121) differentiated from SGG (Sonasal and Bindli) by 504439 SNPs and 78166 InDels. The LRK gene cluster was significantly affected and a truncation mutation in the LRK8 kinase domain was uniquely associated with LGG. Phylogeny with 3000 diverse rice accessions revealed four sequenced genotypes belonged to japonica group and were at the edge of clades indicating source of genetic diversity available in Asian rice population. Five SNPs significantly were associated with grain size/weight and top three SNPs were validated in RIL mapping populations, suggesting this study as a valuable resource for high-throughput genotyping. A contiguous [~]6 Mb polymorphism desert region carrying a major grain weight QTL was identified on chromosome 5 in four sequenced genotypes. Further, among 3000, this region was identified as evolutionary important site with significant positive selection, elevated LD, and multiple selection sweeps, stabilising many domestication-related traits including grain size/weight. The aus group genotype retained more allelic variations in the desert region than japonica and indica, and likely to be one of the differentiation point for aus group. We suggest this desert region as an important evolutionary node that can be selected in breeding programs for improvement of grain yield and quality. All data and analysis can be accessed from RiceSzWtBase database.\n\nSignificance statementBeing an important trait, rice grain size/weight has been under rigorous selection since domestication. However, a link between this trait and domestication is not so directly established. In addition to characterization of novel grain size/weight-associated SNPs, in this study, [~] 6 Mb polymorphism desert region harboring major grain weight QTL was identified on chromosome 5, which turned out to be an evolutionary important site with multiple selection sweeps and introgression events, significantly correlated with domestication-related traits.

plant biology↗