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. 2022 Feb;13(2):3350-3361.
doi: 10.1080/21655979.2022.2027181.

Apigenin analogues as SARS-CoV-2 main protease inhibitors: In-silico screening approach

Affiliations

Apigenin analogues as SARS-CoV-2 main protease inhibitors: In-silico screening approach

Ameny Farhat et al. Bioengineered. 2022 Feb.

Abstract

The COVID-19 new variants spread rapidly all over the world, and until now scientists strive to find virus-specific antivirals for its treatment. The main protease of SARS-CoV-2 (Mpro) exhibits high structural and sequence homology to main protease of SARS-CoV (93.23% sequence identity), and their sequence alignment indicated 12 mutated/variant residues. The sequence alignment of SARS-CoV-2 main protease led to identification of only one mutated/variant residue with no significant role in its enzymatic process. Therefore, Mpro was considered as a high-profile drug target in anti-SARS-CoV-2 drug discovery. Apigenin analogues to COVID-19 main protease binding were evaluated. The detailed interactions between the analogues of Apigenin and SARS-CoV-2 Mpro inhibitors were determined as hydrogen bonds, electronic bonds and hydrophobic interactions. The binding energies obtained from the molecular docking of Mpro with Boceprevir, Apigenin, Apigenin 7-glucoside-4'-p-coumarate, Apigenin 7-glucoside-4'-trans-caffeate and Apigenin 7-O-beta-d-glucoside (Cosmosiin) were found to be -6.6, -7.2, -8.8, -8.7 and -8.0 kcal/mol, respectively. Pharmacokinetic parameters and toxicological characteristics obtained by computational techniques and Virtual ADME studies of the Apigenin analogues confirmed that the Apigenin 7-glucoside-4'-p-coumarate is the best candidate for SARS-CoV-2 Mpro inhibition.

Keywords: SARS-Cov-2 main protease; apigenin analogues; docking; inhibitors.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Structure-based multiple sequence alignment of SARS-CoV-2 Mpro from different variant (6WTT, 2OP9, QVD51579.1, QWF00346.1, QMV29895.1, QRX05355.1, QTN92506.1, QRW91276.1, QNN90050.1, QNN90062.1 and QNN90074.1). Residues invariable among sequences are typed in white on a red background; residues conserved within each group are typed in red on a yellow background. The residue mutated in this study (R279) is indicated in light blue. Secondary structure elements from of Mpro structure are indicated at the top of the alignment with SARS-CoV-2 main proteases (PDB code: 6WTT) .
Figure 2.
Figure 2.
Superimposition of structure of the SARS-CoV-2 Mpro (pdb: 6WTT) (Orange) and model of the SARS-CoV-2 3 Mpro fromTunisian variant QNN90062.1 (pink). The catalytic dyad (Cys-145 and His-41) is colored in red.
Figure 3.
Figure 3.
Interactions of the SARS-CoV-2 Mpro (pdb: 6WTT) with Boceprevir (a), Apigenin (b), Apigenin 7-glucoside-4’-p-coumarate (c), Apigenin 7-glucoside-4’-trans-caffeate (d) and Apigenin 7-O-beta-D-glucoside (Cosmosiin) (e) .
Figure 4.
Figure 4.
The active site of SARS-CoV-2 (a) bound with Boceprevir (b), Apigenin (c), Apigenin 7-glucoside-4’-p-coumarate (d), Apigenin 7-O-beta-D-glucoside (Cosmosiin) (e) and Apigenin 7-glucoside-4’-trans-caffeate (f) .

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