Dock-able linear and homodetic di, tri, tetra and pentapeptide library from canonical amino acids: SARS-CoV-2 Mpro as a case study

Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low toxicity.Although noncanonical residues can always be used,employing only the natural 20 residues restricts the chemical space to a finite dimension allowing for comprehensive in silico screening.Towards this goal,the dataset comprising all possible di-,tri-,and tetra-peptide combinations of the canonical residues has been previously reported.However,with increasing computational power,the comprehensive set of pentapeptides is now also feasible for screening as the comprehensive set of cyclic peptides comprising four or five residues.Here,we provide both the complete and prefiltered libraries of all di-,tri-,tetra-,and penta-peptide sequences from 20 canonical amino acids and their homodetic(N-to-C-terminal)cyclic homologues.The FASTA,simplified molecular-input line-entry system(SMILES),and structure-data file(SDF)-three dimension(3D)libraries can be readily used for screening against protein targets.We also provide a simple method and tool for conducting identity-based filtering.Access to this dataset will accelerate small peptide screening workflows and encourage their use in drug discovery campaigns.As a case study,the developed library was screened against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)main protease to identify potential small peptide inhibitors.

Designing Cyclopentapeptide Inhibitor of Neuraminidase H5N1 Virus Through Molecular and Pharmacology Simulations

Highly Pathogenic Avian Influenza（HPAI） H5N1 has attracted much attention as a potential pandemic virus in humans, which makes death inevitable in humans. Neuraminidase（NA） has an important role in viral replication. Thus, it is an attractive target when designing anti-influenza virus drug. However, evolving viruses cause some anti-viral drugs to be ineffective, as they show resistance to them. Selection of peptides as drug candidates is important for the peptide-receptor activity and good selectivity. Cyclic bonds in the peptide ligand design aim to improve the stability of the system and remove the obstacles in drug metabolism. The design is based on the polarity of the ligand and amino acid residues in the active site of NA. The results are 4200 cyclic pentapeptides as potential lead compounds. Docking simulations were conducted using MOE 2008.10 and were screened based on the value of the binding energy（？Gbinding）. ADME-Tox prediction assay was conducted on the selected ligands.Intra- and inter-molecular interactions, as well as changes in the form of bonds, were tested by molecular dynamics simulations at temperatures of 310 K and 312 K. The results of the docking simulations and toxicity prediction assay show that there are two ligands that have a residual interaction with the target protein： CLDRC and CIWRC. These two ligands have ？Gbindingvalues of –40.5854 and –39.9721 kcal/mol（1 kcal/mol = 4.18 k J/mol）. These ligands are prone to be mutagenic and carcinogenic, and they have a good oral bioavailability. The results show that the molecular dynamics of both ligand CLDRC and CIWRC are more feasible at the temperature of 312 K. At the end,both CIWRC and CLDRC ligands can be used as the drug candidates against H5N1 virus.