Inhibitory Potential Of Black Seed (Nigella Sativa L.) Bioactive Compounds Towards Main Protease Of SARS-CoV-2 : In Silico Study

Abstract

COVID-19, caused by SARS-CoV-2, has become a massive worldwide concern of the 21st century. One potential strategy to block the biochemical pathway of SARS-CoV-2 was by inhibiting the main protease (Mpro), which is a key enzyme on viral replication. Black seed (Nigella sativa L.) has a long history for its use as a traditional medicine. Therefore, we hypothesised that the black seed contains numerous active compounds that could potentially confer inhibitory activity against SARS-CoV-2 viral Mpro. In this study, 24 active compounds from black seed were tested. Compounds were screened using Lipinski's Rules and admetSAR, then docked to viral Mpro 7BQY by AutoDockTools-1.5.6 and AutoDock Vina using a site directed docking approach resulting in affinity energy (∆G) and binding data. We found that the most potential active compound of N. sativa is 3-[(4-Methylphenyl)sulfanyl]-1,3-diphenyl-1-propanone, since its affinity energy was -7.6 kCal.mol-1. Its similarity to N3 inhibitor based on Ligplot analysis and DS were 86.7% and 76.19%, respectively, and the occupancy on binding site based on Ligplot analysis and DS were 90.91% and 81.82%, respectively. These findings can be used as a starting point for further investigation using in vitro and in vivo studies.

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

“…Several 67 secondary metabolites in N. sativa seed were curated from the literature [7,8,[10][11][12][13] and tabulated in Table S1. This number of secondary metabolites is larger than the similar works previously reported [17][18][19][20][21]. The secondary metabolites consist of seventeen monoterpenoids, one diterpenoid, two sesquiterpenoids, six phenylpropanoids, three vitamin E compounds, ten phytosterols, eight triterpenoids, three saponins, three flavonols, and fourteen alkaloids.…”

“…To identify potential inhibitors of M Pro , previous studies [17][18][19][20][21] used the molecular docking approach, which might be insufficient since the method has some limitations [22]. Therefore, the current study employed MD for such a purpose.…”

“…In silico approach allows us to screen the secondary metabolites against M pro without synthesizing the compounds [16]. Several in silico investigations have been reported regarding the potency of N. sativa seed as the natural source of COVID-19 antivirals [17][18][19][20][21]. Khan and his co-workers [17] performed a molecular docking study on seven secondary metabolites in N. Sativa seed.…”

“…Based on their molecular docking study of three secondary metabolites in N. sativa seed, Sumaryada and Pramudita also proposed nigellidine as the best inhibitor against M pro [20]. Meanwhile, using a more extensive data set of 24 secondary metabolites in their molecular docking study, Ferdian and his co-workers found 3-[(4-methylphenyl)sulfanyl]-1,3-diphenyl-1propanone as the best potential inhibitor against M pro [21].…”

Studi In Silico Senyawa Fenolik Madu sebagai Kandidat Inhibitor Mpro SARS-CoV-2

“…Kesamaan dan cakupan area penambatan ikatan residu asam amnino yang mendekati hingga lebih tinggi dari inhibitor N3 diprediksi sebagai inhibitor potensial. 66 Berdasarkan analisis kemiripan dengan ligan acuan N3 dan persentasi area cakupan, sebanyak 2 dari 27 senyawa fenolik madu memiliki persentasi kemiripan dengan N3 dan persentasi area cakupan lebih dari 60% sehingga diprediksi berpotensi untuk menginhibisi reseptor 7BQY secara kuat dan tepat. Kedua senyawa tersebut adalah rutin dan genistein.…”