2-Phenoxyacetamide derivatives as SARS-CoV-2 main protease inhibitor: In silico studies

Pandu Hariyono; Rini Dwiastuti; Muhammad Yusuf; Nurul H Salin; Maywan Hariono

doi:10.1016/j.rechem.2021.100263

2-Phenoxyacetamide derivatives as SARS-CoV-2 main protease inhibitor: In silico studies

Results Chem. 2022 Jan:4:100263. doi: 10.1016/j.rechem.2021.100263. Epub 2021 Dec 12.

Authors

Pandu Hariyono¹, Rini Dwiastuti¹, Muhammad Yusuf², Nurul H Salin³, Maywan Hariono¹

Affiliations

¹ Faculty of Pharmacy, Sanata Dharma University, Campus 3, Paingan, Maguwoharjo, Depok, Sleman 55282, Yogyakarta, Indonesia.
² Chemistry Department, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jatinangor, Sumedang 45363, West Java, Indonesia.
³ Malaysian Institute of Pharmaceuticals and Nutraceuticals, National Institute of Biotechnology Malaysia, Halaman Bukit Gambir, 11900 Bayan Lepas, Pulau Pinang, Malaysia.

Abstract

2-Phenoxyacetamide group has been identified as one of markers in the discovery and development of SARS-CoV-2 antiviral agent through its main protease (M^pro) inhibition pathway. This study aims to study a series of 2-phenoxyacetamide derivatives using in silico method toward SARS-CoV-2 M^pro as the protein target. The study was initiated by employing structure-based pharmacophore to virtually screen and to select the ligands, which have the best fit score (hits) along with the common pharmacophore features being matched. The result shows that from the 11 ligands designed, four ligands are selected as the hits by demonstrating fit score in the range of 56.20 to 65.53 to the pharmacophore model, employing hydrogen bond acceptor (HBA) and hydrophobic (H) as the common features. The hits were then docked into the binding site of the M^pro to see the binding mode of the corresponding hits as well as its affinity. The docking results free energy of binding (ΔG_bind) of the hits are in agreement with the pharmacophore fit score, in the range of -6.83 to -7.20 kcal/ mol. To gain the information of the hits as a potential drug to be developed, the in silico study was further proceed by predicting the mutagenic potency, toxicity and pharmacokinetic profiles. Based on the efficiency percentage, all hits meet the criteria as drug candidates by showing 84-88% leading to a conclusion that 2-phenoxyacetamide derivatives are beneficial to be marked as the lead compound for SARS-CoV-2 M^pro inhibitor.

Keywords: 2-Phenoxyacetamide; In silico; Main protease; SARS-CoV-2.