Identification of potential bioactive natural compounds from Indonesian medicinal plants against 3-chymotrypsin-like protease (3CLpro) of SARS-CoV-2: molecular docking, ADME/T, molecular dynamic simulations, and DFT analysis

• Published in: Journal of biomolecular structure & dynamics Vol. 41; no. 10; pp. 4467 - 4484
• Main Authors: Prasetyo, Wahyu Eko, Purnomo, Heri, Sadrini, Miracle, Wibowo, Fajar Rakhman, Firdaus, Maulidan, Kusumaningsih, Triana
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.07.2023
• Subjects: 3CL; COVID-19; Jamu; Luteolin; Naringenin; pro; COVID-19; 3CLpro; Naringenin; Luteolin; Jamu
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2022.2068071

An outbreak of SARS-CoV-2 (COVID-19) has caused a global health emergency, resulting in hundreds of millions of infections and millions of deaths globally since December 2019. Due to the lack of a particular medicine or treatment approach and the fast spread of the virus around the world, it is imperative to find effective pharmacological molecules to combat the virus. Herein, we carried out docking-based virtual screening of selected 49 bioactive phytochemicals from 20 medicinal plants used in Jamu, an Indonesian traditional herbal medicine along with the 3CL pro inhibitor N3 towards the 3CL pro enzyme of SARS-CoV-2. From a total of 49 bioactive phytochemicals, eleven compounds exhibited good binding affinity against 3CL pro of SARS-CoV-2 (-7.2 to −8.5 kcal/mol). Accordingly, only seven phytochemicals fully obeyed drug-likeness properties. Ultimately, it was observed that both Luteolin and Naringenin have significant interactions with both of the catalytic residues of 3CL pro through hydrogen bonds and hydrophobic interactions, respectively. The drug-like characteristics of Luteolin and Naringenin were also confirmed by pharmacokinetic investigations. Further, an investigation into molecular dynamics (MD) simulations were undertaken to ensure the ligands would remain stable within the binding pocket. Finally, density-functional theory (DFT) calculations revealed the following order for biochemical reactivity: Naringenin > Luteolin > N3. The oxygen and hydrogen atom regions of these investigated ligands are suitable for electrophilic and nucleophilic attacks, respectively. These two bioactive phytochemicals from Tamarindus indica (Luteolin and Naringenin) as well as Citrus aurantifolia (Naringenin) might be potential antagonists of 3CL pro of SARS-CoV-2. Communicated by Ramaswamy H. Sarma.