Exploring the Effect of Ritonavir and TMC-310911 on SARS-CoV-2 and SARS-CoV Main Proteases: Potential From a Molecular Perspective

Abstract

Aim: As coronavirus (CoV) disease 2019-associated pneumonia spreads globally, there has been an urgent need to combat the spread and develop vaccines. Materials & methods: We used an integrated computational algorithm to explore the binding mechanism of TMC-310911/ritonavir (RVT) with SARS-CoV-2 and SARS-CoV main proteases. Results: RVT and TMC-310911 had favorable interactions with the proteases, and these high interactions are facilitated by some significant residues such as Asn133, Gly195 and Gln192. Our study further implicated two important rings in the structure of RVT as a possible chemical culprit in its therapeutic activity. Conclusion: Although there are conflicting clinical results on the therapeutic potency of RVT in the treatment of coronavirus disease 2019, our findings provided molecular insight into the binding mechanism of TMC-310911 and RVT with SARS-CoV-2 and SARS-CoV main proteases.

Propitious Indazole Compounds as β‐ketoacyl‐ACP Synthase Inhibitors and Mechanisms Unfolded for TB Cure: Integrated Rational Design and MD Simulations

“…Subsequently, receptor and inhibitor JSF‐3285 were prepared using the Chimeratool‐1.14 [23,24] and the AutoDockTool‐1.5.6 [25] and optimized (using the Molegro Molecular Viewer‐2.5) [26] for molecular dynamic (MD) simulation study. The unbound and ligand‐bound systems’ preparation involves removing nonstandard molecules, including water, GOL, IPA, and sodium [27] …”

“…The unbound and ligand-bound systems' preparation involves removing nonstandard molecules, including water, GOL, IPA, and sodium. [27] Pharmacophore modeling of JFX-bound KasA protein First, the inhibitor JSF-3285 was simulated at the substrate-binding site of the β-ketoacyl synthase I enzyme for 40 ns to generate a bound conformation of the ligand (Figure 1A). A per-residue energy decomposition study was used to identify the amino acids that contributed the highest energy in the binding of the inhibitor.…”

Oral anti-COVID-19 drugs that were recently evaluated by FDA or EMA: a review

“…Ritonavir is a drug used for the treatment of HIV [124]. It has been suggested by AI as well [125][126][127][128]. It is mostly used along with lopinavir to prolong its half-life with good in vitro effects [129,130], but the results in COVID-19 therapy mostly show that the use of this combination may be not satisfactory [131][132][133][134][135][136][137][138].…”

Databases, DrugBank, and virtual screening platforms for therapeutic development

“…It has exhibited in vitro activity against HIV strains that have developed resistance to other protease inhibitors. SARS-CoV main protease (SARS) is being targeted by researchers to investigate their possible mode of inhibition ( Soremekun et al, 2021 ).…”