Targeting Virus-Host Interaction: An in Silico Approach to Develop Promising Inhibitors Against COVID-19

The entire human population all over the globe is currently facing appalling conditions due tothe spread of infection from COVID-19 (corona virus disease-2019). In the last few monthsenormous amount of studies have been continuously trying to target several potential drugsites to identify a novel therapeutic target. Spike protein of severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) is also being targeted by several scientific groups as a noveldrug target. The spike glycoprotein protein is present on the surface of the virion and binds tothe human angiotensin-converting enzyme-2 (hACE2) membrane receptor thereby promotingits fusion to the host cell membrane. The binding and internalization of the virus is a crucialstep in the process of infection and hence any molecule that can inhibit this, certainly holds asignificant therapeutic value. We have identified AP-NP (2-(2-amino-5-(naphthalen-2-yl)pyrimidin-4-yl)phenol) and AP-4-Me-Ph (2-(2-amino-5-(p-tolyl)pyrimidin-4-yl)phenol)from a group of diaryl pyrimidine derivatives which appear to bind at the interface ofhACE2-SARS-CoV-2S complex (human angiotensin converting enzyme 2 and spikeglycoprotein complex) with a low binding energy (<-8 Kcal/mol). In this in-silico study wealso found that AP-NP interacts with S1 domain of C-terminal part of SARS-CoV-2Showever AP-4-Me-Ph was found to interact with S2 domain of SARS-CoV-2S. The resultsuggested that AP-NP and AP-4-Me-Ph have potential to inhibit the interaction betweenspike protein and hACE2 receptor also AP-4-Me-Ph might be prevent internalization of thevirion within the host. Further in vitro and in vivo study will strengthen these drug candidatesagainst the COVID-19.