De Novo Drug Design of Potential Inhibitors of SARS-CoV-2 Papain-like Protease
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...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | Medical Sciences Forum |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2673-9992/21/1/37 |
| _version_ | 1797379839504678912 |
|---|---|
| author | Edgar Clyde R. Lopez |
| author_facet | Edgar Clyde R. Lopez |
| author_sort | Edgar Clyde R. Lopez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T20:28:51Z |
| format | Article |
| id | doaj.art-405e9d80b3e94b50b4a5ae4cf92d97d7 |
| institution | Directory Open Access Journal |
| issn | 2673-9992 |
| language | English |
| last_indexed | 2024-03-08T20:28:51Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medical Sciences Forum |
| spelling | doaj.art-405e9d80b3e94b50b4a5ae4cf92d97d72023-12-22T14:28:44ZengMDPI AGMedical Sciences Forum2673-99922023-04-012113710.3390/ECB2023-14368De Novo Drug Design of Potential Inhibitors of SARS-CoV-2 Papain-like ProteaseEdgar Clyde R. Lopez0Chemical Engineering Department, Adamson University, 900 San Marcelino St., Ermita, Manila 1000, PhilippinesHere, 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.https://www.mdpi.com/2673-9992/21/1/37SARS-CoV-2COVID-19de novo drug designmolecular dynamics |
| spellingShingle | Edgar Clyde R. Lopez De Novo Drug Design of Potential Inhibitors of SARS-CoV-2 Papain-like Protease Medical Sciences Forum SARS-CoV-2 COVID-19 de novo drug design molecular dynamics |
| title | De Novo Drug Design of Potential Inhibitors of SARS-CoV-2 Papain-like Protease |
| title_full | De Novo Drug Design of Potential Inhibitors of SARS-CoV-2 Papain-like Protease |
| title_fullStr | De Novo Drug Design of Potential Inhibitors of SARS-CoV-2 Papain-like Protease |
| title_full_unstemmed | De Novo Drug Design of Potential Inhibitors of SARS-CoV-2 Papain-like Protease |
| title_short | De Novo Drug Design of Potential Inhibitors of SARS-CoV-2 Papain-like Protease |
| title_sort | de novo drug design of potential inhibitors of sars cov 2 papain like protease |
| topic | SARS-CoV-2 COVID-19 de novo drug design molecular dynamics |
| url | https://www.mdpi.com/2673-9992/21/1/37 |
| work_keys_str_mv | AT edgarclyderlopez denovodrugdesignofpotentialinhibitorsofsarscov2papainlikeprotease |