N-substituted tetrahydro-beta-carboline as mu-opioid receptors ligands: in silico study; molecular docking, ADMET and molecular dynamics approach.

Manipulating intracellular signals by interaction with transmembranal G-protein-coupled receptors (GPCRs) is the way of action of more than 30% of available medicines. Designing molecules against GPCRs is most challenging due to their flexible binding orthosteric and allosteric pockets, a property that lead to different mode and extent of activation of intracellular mediators. Here, in the current study we aimed to design N-substituted tetrahydro-beta-carbolines (THβC's) targeting Mu Opioid Receptors (MORs).

Structural modelling and pharmacology of β-carboline alkaloids as potent 5-HT1A receptor antagonists and reuptake inhibitors.

Serotonin (5-HT) antagonists and reuptake inhibitors (SARIs) are atypical antidepressants for managing major depressive disorder. They are oftentimes applied as adjuvants for ameliorating aftereffects of SSRI antidepressants including insomnia and sexual dysfunction. The few available candidates of this class including lorpiprazole and trazodone also display some daunting side effects, making a continuous search for improved alternatives essential.

Molecular Modelling and Virtual Screening to Identify New Piperazine Derivatives as Potent Human 5-HT1A Antagonists and Reuptake Inhibitors.

Background: Serotonin/5-HT antagonist and reuptake inhibitors (SARIs) ameliorate depression by increasing the terminal 5-HT through the activation of somatodendritic 5-HT1A autoreceptors. In addition to their therapeutic application as standalone antidepressants, they are co-administered with selective serotonin reuptake inhibitors (SSRI) to improve unpleasant side effects associated with SSRI-treated depression. However, only a few of the atypical antidepressants are available and not without some serious aftereffects.

Pathomechanisms, therapeutic targets and potent inhibitors of some beta-coronaviruses from bench-to-bedside.

Since the emergence of their primitive strains, the complexity surrounding their pathogenesis, constant genetic mutation and translation are contributing factors to the scarcity of a successful vaccine for coronaviruses till moment. Although, the recent announcement of vaccine breakthrough for COVID-19 renews the hope, however, there remains a major challenge of accessibility to urgently match the rapid global therapeutic demand for curtailing the pandemic, thereby creating an impetus for further search. The reassessment of results from a stream of experiments is of enormous importance in identifying bona fide lead-like candidates to fulfil this quest.