Pfizer unveils its oral SARS-CoV-2 inhibitor

  title={Pfizer unveils its oral SARS-CoV-2 inhibitor},
  author={Bethany Halford},
  journal={Chemical \& Engineering News},
Design, Synthesis and Evaluation of Fused Bicyclo[2.2.2]octene as a Potential Core Scaffold for the Non-Covalent Inhibitors of SARS-CoV-2 3CLpro Main Protease
The fused bicyclo[2.2. 2.2]octenes can be used as a new potential starting point in the development of non-covalent SARS-CoV-2 3CLpro protease inhibitors and the study substantiates the potential of this versatile scaffold for theDevelopment of biologically active molecules.
Expanding the Repertoire of Low‐Molecular‐Weight Pentafluorosulfanyl‐Substituted Scaffolds
The pentafluorosulfanyl (‐SF5) functional group is of increasing interest as a bioisostere in medicinal chemistry. A library of SF5‐containing compounds, including amide, isoxazole, and oxindole
Hit Expansion of a Noncovalent SARS-CoV-2 Main Protease Inhibitor
The results help explain the strength of this new non-covalent scaffold for Mpro inhibition and inform lead optimization efforts for this series, while demonstrating the effectiveness of a high-throughput computational approach to expanding a pharmacophore library.
Screening for Inhibitors of Main Protease in SARS-CoV-2: In Silico and In Vitro Approach Avoiding Peptidyl Secondary Amides
Although nitro groups were enriched in the substructure of the hit compounds, they did not significantly contribute to the binding interaction in the predicted docking poses, and Physicochemical properties prediction showed good oral absorption, promising candidates for future optimization.
Discovery of SARS-CoV-2 Mpro Peptide Inhibitors from Modelling Substrate and Ligand Binding
Computational mutagenesis scanning was employed to design peptides with improved affinity and which inhibit Mpro competitively, and modelling studies reveal remarkable conservation of hydrogen bonding patterns of the natural Mpro substrates, particularly on the N-terminal side of the scissile bond.
Indole Chloropyridinyl Ester-Derived SARS-CoV-2 3CLpro Inhibitors: Enzyme Inhibition, Antiviral Efficacy, Structure–Activity Relationship, and X-ray Structural Studies
Here, we report the synthesis, structure–activity relationship studies, enzyme inhibition, antiviral activity, and X-ray crystallographic studies of 5-chloropyridinyl indole carboxylate derivatives
Insight into the Binding Energetics of Targeted Reversible Covalent Inhibitors of the SARS-CoV-2 Main Protease
It is found that the inclusion of enhanced sampling techniques such as replica-exchange algorithm in binding free energy calculations can improve the convergence of predicted non-covalent binding freeEnergy estimates of inhibitors binding to the Mpro target.