Mucosa-associated invariant T (MAIT) cells are an important subset of innate lymphocytes that recognize microbial ligands derived from the riboflavin biosynthesis pathway and mediate antimicrobial immune responses. Modulated MAIT cell responses have been noted in different forms of tuberculosis.

Tuberculosis (TB) continues to be a global health crisis, necessitating urgent interventions to address drug resistance and improve treatment efficacy. In this study, we validate lumazine synthase (RibH), a vital enzyme in the riboflavin biosynthetic pathway, as a potential drug target against Mycobacterium tuberculosis (M. tb) using a CRISPRi-based conditional gene knockdown strategy. We employ a high-throughput molecular docking approach to screen ~ 600,000 compounds targeting RibH. Through in vitro screening of 55 shortlisted compounds, we discover 3 compounds that exhibit potent antimycobacterial activity. These compounds also reduce intracellular burden of M. tb during macrophage infection and prevent the resuscitation of the nutrient-starved persister bacteria. Moreover, these three compounds enhance the bactericidal effect of first-line anti-TB drugs, isoniazid and rifampicin. Corroborating with the in silico predicted high docking scores along with favourable ADME and toxicity profiles, all three compounds demonstrate binding affinity towards purified lumazine synthase enzyme in vitro, in addition these compounds exhibit riboflavin displacement in an in vitro assay with purified lumazine synthase indicative of specificity of these compounds to the active site. Further, treatment of M. tb with these compounds indicate reduced production of flavin adenine dinucleotide (FAD), the ultimate end product of the riboflavin biosynthetic pathway suggesting the action of these drugs on riboflavin biosynthesis. These compounds also show acceptable safety profile in mammalian cells, with a high selective index. Hence, our study validates RibH as an important drug target against M. tb and identifies potent antimycobacterial agents.

Polycystic Ovarian Syndrome (PCOS) is the most prevalent hormonal disorder that affects metabolism, ovulation and menstrual cycles. SIRT1 belongs to the Sirtuin family, a group of NAD+ dependent class 3 histone deacetylases. This review explores the correlation between SIRT1 and PCOS and associated mechanisms of action like Insulin resistance, oxidative stress, inflammation and autophagy. Extensive studies have been done on SIRT1, how it was downregulated and contributed to conditions like insulin resistance. How activation of SIRT1 helps by deacetylating the different responsible transcriptional factors is discussed in the mechanisms briefly. Additionally, we discussed the molecular structures of the existing natural and synthetic SIRT1 activators and their roles, which were previously reported, from the chemistry perspective. This review gives insights into the challenges and advantages of SIRT1, which can be a beneficial therapeutic target for PCOS.

Globally, the impact of the coronavirus disease 2019 (COVID-19) pandemic has been enormous and unrelenting with ∼6.9 million deaths and ∼765 million infections. This review mainly focuses on the recent advances and potentially novel molecular tools for viral diagnostics and therapeutics with far-reaching implications in managing the future pandemics. In addition to briefly highlighting the existing and recent methods of viral diagnostics, we propose a couple of potentially novel non-PCR-based methods for rapid, cost-effective, and single-step detection of nucleic acids of viruses using RNA mimics of green fluorescent protein (GFP) and nuclease-based approaches. We also highlight key innovations in miniaturized Lab-on-Chip (LoC) devices, which in combination with cyber-physical systems, could serve as ideal futuristic platforms for viral diagnosis and disease management. We also discuss underexplored and underutilized antiviral strategies, including ribozyme-mediated RNA-cleaving tools for targeting viral RNA, and recent advances in plant-based platforms for rapid, low-cost, and large-scale production and oral delivery of antiviral agents/vaccines. Lastly, we propose repurposing of the existing vaccines for newer applications with a major emphasis on Bacillus Calmette–Guérin (BCG)-based vaccine engineering.

Detection pipeline for Klebsiella pneumoniae using RPA and AgNP.