Background:
Treatment of the Covid-19 pandemic caused by the highly contagious and pathogenic SARS-CoV-2 is a global menace. Day by day this pandemic is getting worse. Doctors, Scientists and Researchers across the world are urgently scrambling for a cure for novel corona virus and continuously working at break neck speed to develop vaccine or drugs. But to date, there are no specific drugs or vaccine available in the market to cope up the virus.
Objective:
The present study helps us to elucidate 3D structures of SARS-CoV-2 proteins and also to identify best natural compounds as potential inhibitors against COVID-19.
Methods:
The 3D structures of the proteins were constructed using Modeller 9.16 modeling tool. Modelled proteins were validated with PROCHECK by Ramachandran plot analysis. In this study a small library of natural compounds (fifty compounds) was docked to the ACE2 binding site of the modelled surface glycoprotein of SARS-CoV-2 using Auto Dock Vina to repurpose these inhibitors for SARS-CoV-2. Conceptual density functional theory calculations of best eight compounds had been performed by Gaussian-09. Geometry optimizations for these molecules were done at M06-2X/ def2-TZVP level of theory. ADME parameters, pharmacokinetic properties and drug likeliness of the compounds were analyzed in the swissADME website.
Results:
In this study we analysed the sequences of surface glycoprotein, nucleocapsid phosphoprotein and envelope protein obtained from different parts of the globe. We have modelled all the different sequences of surface glycoprotein and envelop protein in order to derive 3D structure of a molecular target which is essential for the development of therapeutics. Different electronic properties of the inhibitors have been calculated using DFT through M06-2X functional with def2-TZVP basis set. Docking result at the hACE2 binding site of all modelled surface glycoproteins of SARS-CoV-2 showed that all the eight inhibitors (Actinomycin D, avellanin C, ichangin, kanglemycin A, obacunone, ursolic acid, ansamiotocin P-3 and isomitomycin A) studied here many folds better compared to hydroxychloroquine which has been found to be effective to treat patients suffering fromCOVID-19 pandemic. All the inhibitors meet most of criteria of drug likeness assessment.
Conclusion:
We will expect that eight compounds (Actinomycin D, avellanin C, ichangin, kanglemycin A, obacunone, ursolic acid, ansamiotocin P-3 and isomitomycin A) can be used as potential inhibitors against SARS-CoV-2.
Computational estimation of potential inhibitors from known drugs against the main protease of SARS-CoV-2
