Exploring the Potency of  Nigella sativa  Seed in Inhibiting SARS-CoV-2 Main Protease Using Molecular Docking and Molecular Dynamics Simulations

Ari Hardianto; Muhammad Yusuf; Ika Wiani Hidayat; Safri Ishmayana; Ukun Mochammad Syukur Soedjanaatmadja

doi:10.22146/ijc.65951

Exploring the Potency of Nigella sativa Seed in Inhibiting SARS-CoV-2 Main Protease Using Molecular Docking and Molecular Dynamics Simulations

https://doi.org/10.22146/ijc.65951

Ari Hardianto^(1*), Muhammad Yusuf⁽²⁾, Ika Wiani Hidayat⁽³⁾, Safri Ishmayana⁽⁴⁾, Ukun Mochammad Syukur Soedjanaatmadja⁽⁵⁾

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, West Java, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, West Java, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, West Java, Indonesia
(4) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, West Java, Indonesia
(5) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, West Java, Indonesia
(*) Corresponding Author

Abstract

Coronavirus disease (COVID-19) is a pandemic burdening the global economy. It is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Black cumin (Nigella sativa) seed may contain antivirals for the disease since it was reported to inhibit the human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Main protease (M^pro) is a vital protein for viral replication and a promising target for COVID-19 drug development. Hence, in this study, we intended to uncover the potency of N. sativa seed as the natural source of inhibitors for SARS-CoV-2 M^pro. We collected secondary metabolites in N. sativa seed through a literature search and employed Lipinski’s rule of five as the initial filter. Subsequently, virtual screening campaigns using a molecular docking method were performed, with N3 inhibitor and leupeptin as reference ligands. The top hits were analyzed further using a molecular dynamics simulation approach. Molecular dynamics simulations showed that binding affinities of nigellamine A2 and A3 to M^pro are comparable to that of leupeptin, with median values of -43.9 and -36.2 kcal mol^–1, respectively. Ultimately, this study provides scientific information regarding N. sativa seeds’ potency against COVID-19 and helps direct further wet experiments.

Keywords

antivirals; Mpro; Nigella sativa seeds; secondary metabolites; virtual screening

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DOI: https://doi.org/10.22146/ijc.65951