8-hydroxydihydrosanguinarine and sanguinarine

The unprecedented global pandemic of COVID-19 has created a daunting scenario urging an immediate generation of therapeutic strategy. Interventions to curb the spread of viral infection primarily include setting targets against the virus. Here in this study we target S protein to obstruct the viral attachment and entry and also the M pro to prevent the viral replication. For this purpose, the interaction of S protein and M pro with phytocompounds, sanguinarine and eugenol, and their derivatives were studied using computational tools. Docking studies gave evidence that 8-hydroxydihydrosanguinarine (8-HDS), a derivative of sanguinarine, showed maximum binding affinity with both the targets. The binding energies of the ligand with S protein and M pro scored to be ΔGb -9.4 Kcal/mol and ΔGb -10.3 Kcal/mol, respectively. MD simulation studies depict that the phytocompound could effectively cause structural perturbations in the targets which would affect their functions. 8-Hydroxydihydrosanguinarine distorts the α-helix in the secondary structure of M pro and RBD site of S protein. Protein-protein interaction study in presence of 8-hydroxydihydrosanguinarine also corroborate the above findings which indicate that this polyphenol interferes in the coupling of S protein and ACE2. The alterations in protonation of M pro suggest that the protein structure undergoes significant structural changes at neutral pH. ADME property of 8-hydroxydihydrosanguinarine indicates this could be a potential drug. This makes the phyto-alkaloid a possible therapeutic molecule for anti COVID-19 drug design.

Topics: Antiviral Agents; COVID-19 Drug Treatment; Humans; Molecular Docking Simulation; Molecular Dynamics Simulation; Pyridones; SARS-CoV-2; Viral Nonstructural Proteins

The herb of Chelidonium majus Linn is known to possess a variety of biological activities and applied in the therapy of various infectious diseases.. To evaluate the in vitro antifungal activity of the active components from Chelidonium majus against clinical drug-resistant yeast isolates.. Active compounds were obtained using bioassay-guided method. Six species of yeast fungi were exposed to the compounds. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined according to the standard broth microdilution method.. Of the six compounds determined, 8-hydroxydihydrosanguinarine (1) and 8-hydroxydihydrochelerythrine (2) demonstrated potent activity with the MIC ranges of 2-80 and 4-100 microg/mL, respectively. Dihydrosanguinarine (3), dihydrochelerythrine (4), sanguinarine (5) and chelerythrine (6) had some degree of antifungal activity.. The overall results provided important information for the potential application of the 8-hydroxylated alkaloids from Chelidonium majus in the therapy of serious infection caused by drug-resistant fungi.

Topics: Alkaloids; Antifungal Agents; Benzophenanthridines; Candida; Chelidonium; Drug Evaluation, Preclinical; Drug Resistance; Heterocyclic Compounds, 4 or More Rings; Humans; Isoquinolines; Microbial Sensitivity Tests; Molecular Structure; Plant Extracts; Plants, Medicinal; Reference Standards