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Manuscript.pdf (1.89 MB)
Pharmacophore Analyses of SARS-CoV-2 Active Main Protease Inhibitors Using Pharmacophore Query and Docking Study
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
The coronavirus disease (COVID-19) pandemic is the most important current problem in the
world. Many researchers have focused on approved drugs or new drug candidates to combat
the pandemic. Structural and nonstructural proteins of SARS-CoV-2 have been detected as
targets for prevention of host cell infection or blockade of vital function. The main protease that
plays an essential role in the virus life cycle is the optimal target. To design new inhibitors
against the enzyme, the catalytic active site and substrate-binding site should be well analyzed.
In this study, we generated a pharmacophore model using the cocrystallized pose of an active
SARS-CoV-2 main protease inhibitor. According to the model, the inhibitor inhibits the enzyme
via three hydrogen bond donors, two hydrogen bond acceptors and two aromatic ring
interactions. Moreover, we docked reported active inhibitors of the main protease into the
catalytic active site and detected matches between their pharmacophore models. The results
showed that two close hydrogen acceptor/donor atom pairs and an aromatic ring are essential
for enzyme inhibition.