RESUMO
Omicron is one of the variants of COVID-19 and continuing member of a pandemic. There are several types of vaccines that were developed around the globe to fight against the virus. However, the world is suffering to find suitable drug candidates for the virus. The main protease (Mpro) enzyme of the virus is the best target for finding drug molecules because of its involvement in viral infection and protein synthesis. ZINC-15 is a database of 750 million commercially available compounds. We find 125 compounds having two aromatic rings and amide groups for non-covalent interactions with active site amino acids and functional groups with the capability to bind -SH group of C145 of Mpro through covalent bonding by a nucleophilic addition reaction. The lead compound (Z144) was identified using molecular docking. The non-covalent interactions (NCI) calculations show the interactions between amino acids present in the active site of the protein and the lead molecules are attractive in nature. The density functional-based tight-binding (DFTB) study of the lead compound with amino acids in the active site indicates that Q190 and Q193 play a very critical role in stabilization. The Michael addition of the acrylamide group of the lead molecule at ß-position is facile because the low energy lowest unoccupied molecular orbital (LUMO) is concentrated on the group. From molecular dynamics during 100 ns, it has come to light that strong non-covalent interactions are key for the stability of the lead inside the protein and such binding can fold the protein. The free energy for this interaction is -42.72 kcal mol-1 which was obtained from MM-GB/SA calculations.
RESUMO
Like many galaxies of its size, the Milky Way is a disk with prominent spiral arms rooted in a central bar, although our knowledge of its structure and origin is incomplete. Traditional attempts to understand our Galaxy's morphology assume that it has been unperturbed by major external forces. Here we report simulations of the response of the Milky Way to the infall of the Sagittarius dwarf galaxy (Sgr), which results in the formation of spiral arms, influences the central bar and produces a flared outer disk. Two ring-like wrappings emerge towards the Galactic anti-Centre in our model that are reminiscent of the low-latitude arcs observed in the same area of the Milky Way. Previous models have focused on Sgr itself to reproduce the dwarf's orbital history and place associated constraints on the shape of the Milky Way gravitational potential, treating the Sgr impact event as a trivial influence on the Galactic disk. Our results show that the Milky Way's morphology is not purely secular in origin and that low-mass minor mergers predicted to be common throughout the Universe probably have a similarly important role in shaping galactic structure.
