The devastating impact of Tuberculosis (TB) has been a menace to mankind for decades. The World Health Organization (WHO) End TB Strategy aims to reduce TB mortality up to 95% and 90% of overall TB cases worldwide, by 2035. This incessant urge will be achieved with a breakthrough in either a new TB vaccine or novel drugs with higher efficacy. However, the development of novel drugs is a laborious process involving a timeline of almost 20−30 years with huge expenditure; on the other hand, repurposing previously approved drugs is a viable technique for overcoming current bottlenecks in the identification of new anti-TB agents. The present comprehensive review discusses the progress of almost all the repurposed drugs that have been identified to the present day (∼100) and are in the development or clinical testing phase against TB. We have also emphasized the efficacy of repurposed drugs in combination with already available frontline anti-TB medications along with the scope of future investigations. This study would provide the researchers a detailed overview of nearly all identified anti-TB repurposed drugs and may assist them in selecting the lead compounds for further in vivo/clinical research.

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Background: Mycobacterium tuberculosis (M.tb), the etiological agent of Tuberculosis (TB), is the second leading cause of mortality after COVID-19, with a global death toll of 1.5 million in 2020. The escalating cases of drug-resistant TB are further worsening the current situation and making TB treatment extremely challenging. Thus, it is crucial to look for new anti-TB drugs with novel mechanisms of action and high efficacy. The DnaG of M.tb replication machinery is an essential protein for pathogen survival. Also, its imperative primase activity and lack of structural homology to human proteins, make it a possible target for drug development. Methods: In this presented study, using a computational structure-based drug repurposing approach, Food and drug administration (FDA) approved drugs were virtually screened against M.tb DnaG to identify potential inhibitors. Five drugs viz. Caspofungin, Doxorubicin, Mitoxantrone, Vapreotide, and Zanamivir showed higher molecular docking scores. Further RMSD, RMSF, Rg, SASA, H-bond, and PCA analysis of these drugs and DnaG complexes. Alamar Blue Assay further evaluated the anti-TB activity of these drugs in vitro using H37Ra and H37Rv M.tb strains. Results: The top results for DnaG binding included several FDA-approved drugs, out of which five were selected and subjected to Molecular dynamic simulation and displayed their high binding affinity, stable interaction, more compactness, and reduced atomic motion. The minimum inhibitory concentration of Doxorubicin, Mitoxantrone, and Vapreotide were detected in the range of 0.19-25 µg/ml for both H37Ra, and H37Rv, respectively. Conclusions: Our findings from the study present potential repurposed drug candidates that target DnaG and inhibit M.tb survival. Thorough investigations of these compounds may lead to the discovery of new anti-TB therapeutics.

The elderly population is particularly at risk for developing Chronic Subdural hematomas (CSDH) as a result of trivial trauma. This,  along with the inevitable associated medical co-morbidities, manifests as a challenge for surgical management. The outcomes therefore can sometimes be unfavourable, leading to significant burden on the lives of patients, their families as well as the healthcare set-ups around the world. This seemingly innocuous disease entity can cause poor outcomes in terms of morbidity and mortality for this particular population. Despite having multiple treatment options, both surgical and medical, no consensus has been reached regarding optimal management strategies. We present this article to analyse the management and outcomes as well as challenges faced in the elderly population with CSDH reporting to a tertiary care neurosurgical centre.