An investigation for the interaction of gamma oryzanol with the Mpro of SARS-CoV-2 to combat COVID-19: DFT, molecular docking, ADME and molecular dynamics simulations

COVID-19 has affected more or less every nation across the world and affected the economy very badly. Infection of this virus in human took the life of millions. We have already faced the first and the second waves of COVID-19 and recently, the nations or humanity is afraid of new strain, that is, OMICRON. Considered to highly infectious than the previous strains. Therefore, the researchers are working to find a promising molecule with no or permissible toxicity. In the present work, authors have chosen 10 molecules including the molecules used in curing the infection from nCoV. All the molecules were docked against Mpro of nCoV using iGemdock, a reliable computational tool. Based on the binding energy obtained, it can be seen that only latermovir; remdesivir; zanamivir showed better binding affinity than the gamma oryzanol, the molecule of interest in this work. These three molecules are already in use to cure the patients siffering from the infection of nCoV. But, we need a cost effective and easily available molecule to fight against this viral infection. The binding energy obtained for the formation of complex of gamma oryzanol with Mpro of nCoV through molecular docking is -118.787 kcal/mol. It forms conventional hydrogen bonds with the CYS145 (3.63 angstrom), LEU141 (6.46 angstrom) and SER144 (3.18 and 2.87 angstrom); forms C-H bonds with PHE140 (5.08 angstrom), pi-alkyl interactions with CYS145 (6.72 angstrom); forms alkyl interaction with PRO168 (4.08 and 6.88 angstrom), ALA191 (5.04 angstrom), LEU141 (5.96 and 6.14 angstrom). One interesting information is obtained that the value of log Kp of gamma oryzanol is least means more permeable to skin in comparison of other molecules used in the work. Gamma oryzanol in known for to its biological potency like it can modulate the oxidative stress as well as inflammation. DFT calculations of gamma oryzanol (GO) was made at different temperature and no change in the delocalization of electron density as well no change in free energy is observed. Molecular dynamics (MD) simulations of gamma oryzanol with the Mpro of nCoV at different temperatures was performed. The formation of the complex between GO and Mpro of CoV at 290 K, 300 K, 310 K and 320 K for 100 ns was investigated. It has been observed that the effective binding is observed at 290 K, therefore, it can be said that the inhibition of the Mpro of nCoV with GO is maximum at 290 K.