Biology subjects

Bokolia, N. P.

Publications and source records attributed to Bokolia, N. P..

4 recordsLinked to original sources

bioRxiv2023

A novel vitamin C analog acts as a potent bio-enhancer to augment the activities of anti-tuberculosis drugs against Mycobacterium tuberculosis

Mycobacterium tuberculosis is a deadly pathogen that claims millions of lives every year. Current research focuses on finding new anti-tuberculosis drugs that are safe and effective, with lesser side effects and toxicity. One important approach is to identify bio-enhancers that can improve the effectiveness of anti-tuberculosis drugs, resulting in reduced doses and shortened treatment times. We investigated the use of vitamin C-derived isotetrones as bio- enhancer agents. In this context, our results revealed that the lead compound C11 inhibits growth, improves MIC/MBC, and enhances the killing of M. tuberculosis H37Rv strain when used in combination with first-line and injectable anti-TB drugs in a dose-dependent manner. The combination of C11 and rifampicin also reduced the generation of spontaneous mutants against rifampicin and reached a mutation prevention concentration (MPC) with moderate rifampicin concentrations. The identified compounds were proven to be effective against the MDR strain of M. tuberculosis and non-cytotoxic in HepG2 cells. We also found that C11 induced the generation of reactive oxygen species (ROS) inside macrophages and within bacteria, resulting in better efficacy.

microbiology↗

bioRxiv2022

Identification of genomic signatures and multiple lineage markers from the second and third wave samples of COVID-19 in Western Rajasthan, India

Most of the mutations occurred in SARS-CoV-2 are either relatively neutral or swiftly purged. However, some mutations have altered the functional aspects in terms of infectivity and transmission, host-viral interactions, disease severity and immune or vaccine escape. There are emerging evidence that certain mutations are jeopardizing the immune based therapies. The present research report is focused on the identification of genomic signatures of SARS-CoV-2 variant that caused mortality during second and third wave of COVID-19 in Western Rajasthan, India. We identified that Delta clade of SARS-CoV-2 is the predominant cause of mortality during second wave and even third wave in Western Rajasthan, India. Importantly, this study also revealed the unique and common substitution mutations within the spike domain, those are present in mortality and survived persons during the second and third wave of COVID-19 in India. In addition, this study also revealed the multiple lineage markers (Delta and Omicron), that would update with insightful understanding in the clade development of SARS-CoV-2.

molecular biology↗

bioRxiv2022

Identification of consensus hairpin loop structure among the negative sense sub-genomic RNAs of SARS-CoV-2

SARS-CoV-2 is the causative agent of worldwide pandemic disease COVID-19. SARS-CoV-2 bears positive sense RNA genome, that have organized and complex pattern of replication/transcription process including the generation of subgenomic RNAs. Transcription regulatory sequences (TRS) have important role in the pausing of replication/transcription and generation of subgenomic RNAs. In the present bioinformatics analysis a consensus secondary structure was identified among negative sense subgenomic RNAs at the adjacent of initiation codon. This study proposed that consensus structured domain could involve in mediating the long pausing of replication/transcription complex and responsible for subgenomic RNA production.

bioinformatics↗

bioRxiv2020

Regulation of polyphosphate glucokinase gene expression through co-transcriptional processing in Mycobacterium tuberculosis H37Rv

Transcription is the process that allows the simultaneous folding of RNA molecules, known as co-transcriptional folding. This folding determines the functional properties of RNA molecules and possibly having a critical role during the synthesis as well. This functioning includes the characterized properties of riboswitches and ribozymes as well, which is significant when the transcription rate is comparable to the cellular environment. This study aims to discover a novel non-coding region that is important in the genetic expression of Mycobacterium tuberculosis. In this work, we identified a novel non-coding element of polyphosphate glucokinase (ppgk) gene that undergoes cleavage activity during the transcriptional process in Mycobacterium tuberculosis. We revealed that cleavage occurs within the nascent RNA, and the resultant cleaved 3RNA fragment carries the Shine-Dalgarno (SD) sequence and expression platform. Site-specific mutations provide a strong correlation between the disruption of cleavage activity and expression of ppgk gene. We concluded that co-transcriptional processing at the noncoding region as the required mechanism for ppgk expression that remains constitutive within the bacterial environment. The underlying reason for ppgk mRNA processing and expression is correlated because the non-coding counterpart adopts a hairpin domain that sequesters ribosomal binding site. Thus, the mRNA processing at the immediate upstream of Shine-Dalgarno sequence is required to prevent this sequestration and subsequent expression as well. This study defines the molecular mechanism that is dependent on the transient but highly active structural features of the nascent RNA.

molecular biology↗