Identification of Potential Natural Bioactive Compounds of Indonesian Medicinal Plants Against SARS-CoV-2 3-chymotrypsin-like Protease (3CLpro): Molecular Docking, ADME/T, Molecular Dynamics Simulations and DFT Analysis

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J Biomol Struct Dyn. April 2022 26:1-18. doi: 10.1080/07391102.2022.2068071. Online ahead of print.


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 worldwide since December 2019. Due to the lack of a drug or a particular therapeutic approach and the rapid spread of the virus in the world, it is imperative to find effective pharmacological molecules to fight against the virus. Here, we performed a virtual screen based on docking of 49 bioactive phytochemicals selected from 20 medicinal plants used in jamua traditional Indonesian herbal medicine with 3CLpro N3 inhibitor to 3CLpro SARS-CoV-2 enzyme. Of a total of 49 bioactive phytochemicals, eleven compounds showed good binding affinity against 3CLpro SARS-CoV-2 (-7.2 to -8.5 kcal/mol). As a result, only seven phytochemicals fully obeyed drug-like properties. Ultimately, it was observed that luteolin and naringenin have significant interactions with both catalytic residues of 3CLpro via hydrogen bonds and hydrophobic interactions, respectively. The drug characteristics of luteolin and naringenin have also been confirmed by pharmacokinetic studies. Additionally, investigation of molecular dynamics (MD) simulations was undertaken to ensure that the ligands would remain stable in 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 attack, respectively. These two bioactive phytochemicals of Tamarindus indica (luteolin and naringenin) as well as Citrus aurantifolia (naringenin) could be potential 3CL antagonistspro of SARS-CoV-2. Communicated by Ramaswamy H. Sarma.

PMID:35470785 | DOI: 10.1080/07391102.2022.2068071

Alvin J. Chase