Dra. Gerli-Candia, Lorena

A bacterial biofilm is a cluster of bacterial cells embedded in a self-produced matrix of extracellular polymeric substances such as DNA, proteins, and polysaccharides. Several diseases have been reported to cause by bacterial biofilms, and difficulties in treating these infections are of concern. This work aimed to identify the inhibitor with the highest binding affinity for the receptor protein by screening various inhibitors obtained from Azorella species for a potential target to inhibit dispersin B. This work shows that azorellolide has the highest binding affinity (− 8.2 kcal/mol) among the compounds tested, followed by dyhydroazorellolide, mulinone A, and 7-acetoxy-mulin-9,12-diene which all had a binding affinity of − 8.0 kcal/mol. To the best of our knowledge, this is the first study to evaluate and contrast several diterpene compounds as antibacterial biofilm chemicals. Methods: Here, molecular modelling techniques tested 49 diterpene compounds of Azorella and six FDA-approved antibiotics medicines for antibiofilm activity. Since protein-like interactions are crucial in drug discovery, AutoDock Vina was initially employed to carry out structure-based virtual screening. The drug-likeness and ADMET properties of the chosen compounds were examined to assess the antibiofilm activity further. Lipinski’s rule of five was then applied to determine the antibiofilm activity. Then, molecular electrostatic potential was used to determine the relative polarity of a molecule using the Gaussian 09 package and GaussView 5.08. Following three replica molecular dynamic simulations (using the Schrodinger program, Desmond 2019-4 package) that each lasted 100 ns on the promising candidates, binding free energy was estimated using MM-GBSA. Structural visualisation was used to test the binding affinity of each compound to the crystal structure of dispersin B protein (PDB: 1YHT), a well-known antibiofilm compound.

COVID-19 is a zoonotic viral disease caused by the SARS-CoV-2 virus. Its abrupt outbreak has caused a tremendous challenge to public health systems due to the rapid spread of the virus. In this sense, a great deal of work has been focused on finding substances from herbal plants to be used against this virus. In order to investigate the molecular interactions between natural metabolites from Algerian herbal plants and the SARS-CoV-2 protease Mpro, computational docking and molecular dynamics were used, also the drug likeness degree and in silico ADMET prediction were carried out in this study. warfarin and catalponol preferentially binds to a pocket of the SARS-Cov-2 Mpro active site that is made up of residues His 41 to Glu 166 and Leu 27 to His 163 with a relatively low binding energy of -7.1 and -6.6 kcal/mol respectively. Dynamic molecular assay further established that only warfarin managed to stay in the active site. The results suggest that warfarin may be an interesting candidate for development as a medical treatment of COVID-19 and more research is proposed, without disregarding its toxicity which deserves to be well studied.