In silico elucidation revealed SARS CoV and MERS CoV Drug Compounds could be Potential Therapeutic Candidates against Post Fusion Core (S2) Protein of Novel Coronavirus (2019-nCov)

Abstract Novel coronavirus (2019-nCoV), since its emergence from Wuhan China in December 31, 2019 is still uncontrolled and has raised attention around the globe. According to World health organization, up to March 20, 2020, globally 209,839 confirmed cases of COVID-19 have been reported along with 8778 deaths. 2019-nCoV is likely to be a recombinant of different coronaviruses such as SARS CoV and MERS CoV. Recent developments revealed that glycosylated spike (S) protein of 2019-nCov is contributing significantly in facilitating 2019- nCov infection in human body. The subunit (S1) of spike protein facilitates 2019-nCov binding with host cells’ receptors, while S2 subunit (post fusion core of 2019-nCov) is a key factor in fusion of 2019-nCov with host cell membrane and subsequent inoculation of its DNA in to the host cell. Therefore, in coronavirus infection, membrane fusion and receptor binding are critical. And if active sites of 2019-nCov spike protein S2 (post fusion core of 2019-nCov) are blocked, this may reduce COVID-19 infections in human. We use clustering based drug-drug interaction (DDI) networks and drug repositioning approach based on modularity to inhibit the membrane fusion and receptor binding capacity of 2019-nCov. About 150 drug compounds effective against SARS-CoV and MERS-CoV were retrieved, and screened on the basis of Lipinski rule of five. Clusters and strongly interacted DDI networks were generated in accordance to their modularity class, average path length and density. Promising drug candidates were then filtered by toxicity indicator and molecular docking. Our finding reveals that ZINC000029038525 and ZINC000029129064 drug compounds have significant binding potential with active sites of post fusion core of 2019-nCov ‘S2’ subunit and may inhibit membrane fusion and receptor binding capacity of 2019-nCov. Therefore, these drug compounds alone or in amalgamation could be strong and more effective therapeutic candidates against 2019-nCov infections.