| Summary: | Here, potential inhibitors of the SARS-CoV-2 papain-like protease (PL<sup>pro</sup>) are reported. A drug molecule (PL<sup>pro</sup>-50), designed de novo using generative neural networks, interacts with PL<sup>pro</sup> via hydrogen bonding, forming a salt bridge, and π–π stacking, making it a promising drug against PL<sup>pro</sup>. PL<sup>pro</sup>-50 has an excellent ADMET profile with good absorbability, high clearance, and low toxicity. Molecular dynamics analysis revealed the stability of the receptor–ligand complex of PL<sup>pro</sup>-50 and PL<sup>pro</sup>. An organic retrosynthesis study showed the feasibility of PL<sup>pro</sup>-50 to be synthesized using low-cost starting materials. Further studies should be performed to determine whether the determined drug candidates are efficacious in treating COVID-19 infections.
|
|---|