Covid-19: estudo de docking molecular com fármacos

Abstract

Since the beginning of the Covid-19 pandemic, research groups have used in silico studies to screen potentially inhibitors for SARS-CoV-2 virus, where spike protein is the main target examines. Among these is the molecular docking, relevant in the virtual screening of structurally specific drugs, because it mimics the behavior of small molecules. Due to the urgency to find effective and safe therapies for Covid-19, strategies such as drug repositioning were widely used. With mutations leading to new variants, some selected drugs showed less affinity for their targets. The objective of this work was to perform blind docking between the drugs rendesivir, baricitinib, molnupiravir and dexamethasone with the protein Spike of the gamma, delta and omicron (BA.1) variants to obtain the best conformation of the ligands, the affinity values, as well as examine the intermolecular interactions of the complex. For this purpose, the three-dimensional structures of the drugs were optimized and the protein structures were prepared. The molecular docking proved to be adequate, with RMSD value equal to 1.2061 Å. The complexes with lower Gibbs free energies were: remdesivir - S omicron (-7.5 kcal/mol), baricitinib - S omicron (-7.0 kcal/mol), molnupiravir - S gamma (-6.6 kcal/mol) and dexamethasone - S gamma (-7.9 kcal/mol). All ligands anchored in the N-terminal region of the protein. The formation of complexes was spontaneous, and the rendesivir and baricitinib had higher affinity for the protein S variant omiron (BA.1), while the molnupiravir and dexamethasone had higher affinity for the protein S variant gamma. The most recurrent intermolecular interactions were hydrogen bonds as well as hydrophobic interactions, being relevant to the molecular recognition process of the drugs. For more conclusive studies one can approach molecular dynamics strategies.