Biology subjects

Sehgal, D.

Publications and source records attributed to Sehgal, D..

3 recordsLinked to original sources

bioRxiv2023

Interaction of SCoV-2 NSP7 or NSP8 alone may cause constriction of the RNA entry channel in NSP12: Implications for novel RdRp inhibitor drug discovery

RNA-dependent RNA polymerase (RdRP) is a critical component of the RNA virus life cycle, including SCoV-2. Among the Coronavirus-encoded proteins, non-structural protein 12 (NSP12) exhibits polymerase activity in collaboration with one unit of NSP7 and two units of NSP8, constituting the RdRp holoenzyme. While there is abundant information on SCoV-2 RdRp-mediated RNA replication, the influence of interplay among NSP12, NSP7, and NSP8 on template RNA binding and primer extension activity remains relatively unexplored and poorly understood. Here, we recreated a functional RdRp holoenzyme in vitro using recombinant SCoV-2 NSP12, NSP7, and NSP8, and established its functional activity. Subsequently, molecular interactions among the NSPs in the presence of a variety of templates and their effects on polymerase activity were studied, wherein we found that NSP12 alone exhibited notable polymerase activity that increased significantly in the presence of NSP7 and NSP8. However, this activity was completely shut down, and the template RNA-primer complex was detached from NSP12 when one of the two cofactors was present. Through computational analysis, we found that the template RNA entry channel was more constricted in the presence of one of the two cofactors, which was relatively more constricted in the presence of NSP8 compared to that in the presence of NSP7. In conclusion, we report that NSP7 and NSP8 together synergise to enhance the activity of NSP12, but antagonise when present alone. Our findings have implications for novel drug development, and compounds that obstruct the binding of NSP7 or NSP8 to NSP12 can have lethal effects on viral RNA replication.

molecular biology↗

bioRxiv2023

The International Weed Genomics Consortium: Community Resources for Weed Genomics Research

The International Weed Genomics Consortium is a collaborative group of researchers focused on developing genomic resources for the study of weedy plants. Weeds are attractive systems for basic and applied research due to their impacts on agricultural systems and capacity to swiftly adapt in response to anthropogenic selection pressures. Our goal is to use genomic information to develop sustainable and effective weed control methods and to provide insights about biotic and abiotic stress tolerance to assist crop breeding. Here, we outline resources under development by the consortium and highlight areas of research that will be impacted by these enabling resources.

genomics↗

bioRxiv2022

Allele mining, evolutionary genetic analysis of TaHKT1;5 gene and evaluation of salinity stress in selected lines of wheat.

This study reports the novel allelic diversity in HKT 1;5 gene (High Affinity Potassium Transporter) in bread wheat and its phylogenetic relationship among the paralogs/orthologs of in Triticum aestivum and its wild relatives. HKT 1;5 gene is a known and pivotal gene associated with the salinity tolerance in plants upon the discrimination of K+ over Na+ in leaves without change in Na+ concentration in root. This gene was sequenced in a diverse collection of bread wheat, durum wheat, wild relatives, and ditelosomic lines. Sequence analysis in bread wheat led to the identification of four alleles, which could be distinguished by number of SNPs. Sequence comparison between monocot bread wheat and dicot Arabidopsis thaliana revealed that the HKT1;5 gene is conserved at level of exonic regions; however, the presence of transposable elements especially in intronic regions is further intriguing towards evolutionary relatedness. Two paralogous or major alleles observed in Triticum monoccum and Aegilops tauschii were further categorized as sub-alleles based on their SNPs comparison. This gene was absent in T. urartu in accordance with existing evidence, while it was found in A. speltoides (an allelic variant) with a few base pairs insertion in the exon1 region causing a frameshift mutation with an altered amino acids and genomic database mining unveiled additional alleles in this species. Ditelosomic lines with 4DL and 4DS chromosomes revealed a higher similarity with bread and durum wheat respectively. Phylogenetic studies of HKT1;5 orthologs from different Poaceae species revealed the occurrence of five different ortholog groups with taxonomic consistency. Phenotyping based salinity stress experiment distinguished the unknown lines for salinity tolerance and sensitiveness in comparison with known reference lines and possible allelic comparison was made. The salinity stress analysis further revealed that some known drought/heat tolerance lines showed slightly better salinity tolerance with mean values and variability of traits than known saline tolerant wheat line at controlled ambient.

genetics↗