Binding Mechanism of the Active Form of Molnupiravir to RdRp of SARS-CoV-2 and Designing Potential Analogues: Insights from Molecular Dynamics Simulations.

Molnupiravir, an FDA-approved nucleoside prodrug for treating COVID-19, converts into N4-hydroxycytidine triphosphate (NHC-TP), which integrates into SARS-CoV-2 RNA by its RNA-dependent RNA polymerase (RdRp) causing lethal mutations in viral proteins. Due to the risk of RdRp-mediated drug resistance and potential off-target effects on host polymerases (e.g.

Pharmacology and Therapeutic Potential of Benzothiazole Analogues for Cocaine Use Disorder.

Pharmacological targeting of the dopamine D receptor (DR)─expressed in brain regions that control cognition, attention, and decision-making─could be useful for several neuropsychiatric disorders including substance use disorders (SUDs). This study focused on the synthesis and evaluation of a novel series of benzothiazole analogues designed to target DR. We identified several compounds with high DR binding affinity ( ≤ 6.

Discovering new potential inhibitors to SARS-CoV-2 RNA dependent RNA polymerase (RdRp) using high throughput virtual screening and molecular dynamics simulations.

RNA dependent RNA polymerase (RdRp), is an essential in the RNA replication within the life cycle of the severely acute respiratory coronavirus-2 (SARS-CoV-2), causing the deadly respiratory induced sickness COVID-19. Remdesivir is a prodrug that has seen some success in inhibiting this enzyme, however there is still the pressing need for effective alternatives. In this study, we present the discovery of four non-nucleoside small molecules that bind favorably to SARS-CoV-2 RdRp over the active form of the popular drug remdesivir (RTP) and adenosine triphosphate (ATP) by utilizing high-throughput virtual screening (HTVS) against the vast ZINC compound database coupled with extensive molecular dynamics (MD) simulations.

Mechanistic insight on the remdesivir binding to RNA-Dependent RNA polymerase (RdRp) of SARS-cov-2.

The RNA-dependent RNA polymerase (RdRp) is a key enzyme which regulates the viral replication of SARS-CoV-2. Remdesivir (RDV) is clinically used drug which targets RdRp, however its mechanism of action remains elusive. This study aims to find out the binding dynamics of active Remdesivir-triphosphate (RDV-TP) to RdRp by means of molecular dynamics (MD) simulation.