De novo Drug Design of Potential Inhibitors of the Receptor Binding Domain of SARS-CoV-2 Variants

Edgar Clyde Lopez

doi:10.3390/ECB2023-14371

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De novo Drug Design of Potential Inhibitors of the Receptor Binding Domain of SARS-CoV-2 Variants

Edgar Clyde Lopez

¹ Nanotechnology Research Laboratory, Department of Chemical Engineering, University of the Philippines Diliman, Quezon City, Philippines
² Department of Chemical Engineering, University of Santo Tomas, España Blvd., Sampaloc, Manila, Philip-pines

Academic Editor: Sílvia A. Sousa

Published: 24 April 2023 by MDPI in The 2nd International Electronic Conference on Biomedicines session Frontiers of biomedicine in SARS-CoV-2

https://doi.org/10.3390/ECB2023-14371

Abstract:

Here, novel potential inhibitors of SARS-CoV-2 variants were designed de novo using generative neural networks. The top-performing ligand based on docking performance and ADMET profile is CID #526. It forms several hydrogen bonds with the wild SARS-CoV-2, indicating its potential as an inhibitor of the receptor binding domain. Mutated variants of the RBD also showed good interactions with CID #526, implying the inhibitory properties of our top-performing compound against various variants. Molecular dynamics analysis showed a stable ligand-RBD complex. As our computer-aided organic retrosynthesis study implied, CID #526 can easily be synthesized using low-cost starting molecules. Overall, the generated ligands merit further investigation to determine their efficacy and safety as a treatment against COVID-19.

Keywords: SARS-CoV-2; COVID-19; de novo drug design; molecular dynamics

Supplementary material: Download Supplementary material View paper

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Edgar Clyde Lopez