Singh, Atul Kumar; Kushwaha, Prem Prakash; Prajapati, Kumari Sunita; Shuaib, Mohd; Gupta, Sanjay; Kumar, Shashank published the artcile< Identification of FDA approved drugs and nucleoside analogues as potential SARS-CoV-2 A1pp domain inhibitor: An in silico study>, Formula: C21H27N7Na2O14P2, the main research area is FDA approved drug nucleoside analog SARSCoV2 A1pp domain inhibitor; A1pp domain; FDA approved Drugs; In silico; Macro domain; Nucleoside analogues; SARS-CoV-2.
Coronaviruses are known to infect respiratory tract and intestine. These viruses possess highly conserved viral macro domain A1pp having ADP (ADP)-ribose binding and phosphatase activity sites. A1pp inhibits ADP (ADP)-ribosylation in the host and promotes viral infection and pathogenesis. We performed in silico screening of FDA approved drugs and nucleoside analog library against the recently reported crystal structure of SARS-CoV-2 A1pp domain. Docking scores and interaction profile analyses exhibited strong binding affinity of eleven FDA approved drugs and five nucleoside analogs NA1 (-13.84), nadide (-13.65), citicholine (-13.54), NA2 (-12.42), and NA3 (-12.27). The lead compound NA1 exhibited significant hydrogen bonding and hydrophobic interaction at the natural substrate binding site. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface (SASA), hydrogen bond formation, principle component anal., and free energy landscape calculations for NA1 bound protein displayed stable complex formation in 100 ns mol. dynamics simulation, compared to unbound macro domain and natural substrate adenosine-5-diphosphoribose bound macro domain that served as a pos. control. The mol. mechanics Poisson-Boltzmann surface area anal. of NA1 demonstrated binding free energy of -175.978 ± 0.401 kJ/mol in comparison to natural substrate which had binding free energy of -133.403 ± 14.103 kJ/mol. In silico anal. by modeling tool ADMET and prediction of biol. activity of these compounds further validated them as putative therapeutic mols. against SARS-CoV-2. Taken together, this study offers NA1 as a lead SARS-CoV-2 A1pp domain inhibitor for future testing and development as therapeutics against human coronavirus.
Computers in Biology and Medicine published new progress about ADP ribosylation. 606-68-8 belongs to class chiral-phosphine-ligands, and the molecular formula is C21H27N7Na2O14P2, Formula: C21H27N7Na2O14P2.
Referemce:
Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate