PCSK9 inhibitors as safer therapeutics for atherosclerotic cardiovascular disease (ASCVD): Pharmacophore design and molecular dynamics analysis.

Cardiovascular disorders are still challenging and are among the deadly diseases. As a major risk factor for atherosclerotic cardiovascular disease, dyslipidemia, and high low-density lipoprotein cholesterol in particular, can be prevented primary and secondary by lipid-lowering medications. Therefore, insights are still needed into designing new drugs with minimal side effects.

Structural Insights into the Role of Pseudouridimycin Binding in Disruption of Bacterial RNA Polymerase Bridge Helix Conformational Arrangement.

Background: The bridge helix (BH) is a crucial region in bacterial RNA polymerase (RNAP) catalysis. It plays an essential role in the nucleotide addition cycle (NAC) by performing many modulated rearrangements and conformational changes. Any changes in the bridge helix conformational arrangements could perturb the NAC.

Microbes, not humans: exploring the molecular basis of Pseudouridimycin selectivity towards bacterial and not human RNA polymerase.

Objective: Bacterial RNA polymerase (bRNAP) represent a crucial target for curtailing microbial activity but its structural and sequence similarities with human RNA polymerase II (hRNAPII) makes it difficult to target. Recently, Pseudouridimycin (PUM), a novel nucleoside analogue was reported to selectively inhibit bRNAP and not hRNAP. Till date, underlying mechanisms of PUM selectivity remains unresolved, hence the aim of this study.