Abstract
Considering the urgency of the COVID-19 pandemic, we developed a receptor-based pharmacophore model for identifying FDA-approved drugs and hits from natural products. The COVID-19 main protease (Mpro) was selected for the development of the pharmacophore model. The model consisted of a hydrogen bond acceptor, donor, and hydrophobic features. These features demonstrated good corroboration with a previously reported model that was used to validate the present model, showing an RMSD value of 0.32. The virtual screening was carried out using the ZINC database. A set of 208,000 hits was extracted and filtered using the ligand pharmacophore mapping, applying the lead-like properties. Lipinski’s filter and the fit value filter were used to minimize hits to the top 2000. Simultaneous docking was carried out for 200 hits for natural drugs belonging to the FDA-approved drug database. The top 28 hits from these experiments, with promising predicted pharmacodynamic and pharmacokinetic properties, are reported here. To optimize these hits as Mpro inhibitors and potential treatment options for COVID-19, bench work investigations are needed.
Highlights
There is currently no available medication for the treatment of COVID-19
The model developed through LUDI was revalidated here using Molegro Virtual Docker (MVD) 6.0 [18]
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Summary
There is currently no available medication for the treatment of COVID-19. National regulatory agencies are evaluating certain COVID-19 vaccinations, and one has been approved in some countries. Wide trials of multiple vaccine candidates have shown promising preliminary findings, and more candidates will likely be sent to the regulatory authorities for approval. With the onset of the pandemic, the need to pursue an efficient treatment is more urgent than at any other moment. Scientists from various fields of expertise around the world are seeking to identify the most effective treatments, whether they are already proven to cure other diseases or are novel compounds (synthetic/natural), that can address the SARS-CoV2 mechanism by which the virus attacks and replicates in human cells [2]
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