Biological and Medicinal Chemistry

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 to
the spread of infection from COVID-19 (corona virus disease-2019). In the last few months
enormous amount of studies have been continuously trying to target several potential drug
sites to identify a novel therapeutic target. Spike protein of severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) is also being targeted by several scientific groups as a novel
drug target. The spike glycoprotein protein is present on the surface of the virion and binds to
the human angiotensin-converting enzyme-2 (hACE2) membrane receptor thereby promoting
its fusion to the host cell membrane. The binding and internalization of the virus is a crucial
step in the process of infection and hence any molecule that can inhibit this, certainly holds a
significant 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 of
hACE2-SARS-CoV-2S complex (human angiotensin converting enzyme 2 and spike
glycoprotein complex) with a low binding energy (<-8 Kcal/mol). In this in-silico study we
also found that AP-NP interacts with S1 domain of C-terminal part of SARS-CoV-2S
however AP-4-Me-Ph was found to interact with S2 domain of SARS-CoV-2S. The result
suggested that AP-NP and AP-4-Me-Ph have potential to inhibit the interaction between
spike protein and hACE2 receptor also AP-4-Me-Ph might be prevent internalization of the
virion within the host. Further in vitro and in vivo study will strengthen these drug candidates
against the COVID-19.


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Supplementary material

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Figure and legends
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Supplementary Material