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. 2022 Jul 20;11(14):1886.
doi: 10.3390/plants11141886.

The Computational Preventive Potential of the Rare Flavonoid, Patuletin, Isolated from Tagetes patula, against SARS-CoV-2

Ahmed M Metwaly  1   2 , Eslam B Elkaeed  3 , Bshra A Alsfouk  4 , Abdulrahman M Saleh  5 , Ahmad E Mostafa  1 , Ibrahim H Eissa  5
Affiliations

The Computational Preventive Potential of the Rare Flavonoid, Patuletin, Isolated from Tagetes patula, against SARS-CoV-2

Ahmed M Metwaly et al. Plants (Basel). .

Abstract

The rare flavonoid, patuletin, was isolated from the flowers of Tagetes patula growing in Egypt. The rarity of the isolated compound inspired us to scrutinize its preventive effect against COVID-19 utilizing a multi-step computational approach. Firstly, a structural similarity study was carried out against nine ligands of nine SARS-CoV-2 proteins. The results showed a large structural similarity between patuletin and F86, the ligand of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Then, a 3D-Flexible alignment study of patuletin and F86 verified the proposed similarity. To determine the binding opportunity, patuletin was docked against the RdRp showing a correct binding inside its active pocket with an energy of -20 kcal/mol that was comparable to that of F86 (-23 kcal/mol). Following, several MD simulations as well as MM-PBSA studies authenticated the accurate binding of patuletin in the RdRp via the correct dynamic and energetic behaviors over 100 ns. Additionally, in silico ADMET studies showed the general safety and drug-likeness of patuletin.

Keywords: 3D-Flexible alignment; ADMET; MD simulations; SARS-CoV-2 RNA-dependent RNA polymerase; Tagetes patula; molecular docking; molecular similarity; patuletin; toxicity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patuletin’s chemical structure.
Figure 2
Figure 2
The co-crystallized ligands of SARS-CoV-2 proteins and patuletin.
Figure 3
Figure 3
The results of similarity analysis of the considered ligands and patuletin.
Figure 4
Figure 4
Flexible alignment of patuletin (pink) with F86 (turquoise).
Figure 5
Figure 5
Superimposition of docked F86 (green) and the original one (pink) in RdRp’s active pocket.
Figure 6
Figure 6
(A) The 3D, (B,C) surface mapping of F86 in RdRp’s active site.
Figure 6
Figure 6
(A) The 3D, (B,C) surface mapping of F86 in RdRp’s active site.
Figure 7
Figure 7
(A) The 3D, (B) 2D, and (C) surface mapping of patuletin in RdRp’s active site.
Figure 7
Figure 7
(A) The 3D, (B) 2D, and (C) surface mapping of patuletin in RdRp’s active site.
Figure 8
Figure 8
ADMET study of patuletin and remdesivir.
Figure 9
Figure 9
MD’s results; (A) RMSD values of the patuletin–RdRp complex, (B) RMSF of the patuletin–RdRp complex, (C) Rg of the patuletin–RdRp complex, (D) SASA of the patuletin–RdRp complex, (E) H-bonding of the patuletin–RdRp complex.
Figure 10
Figure 10
Conformational structures for the patuletin and RdRp at the first (A) and 100th (B) nanoseconds of the MD run.
Figure 10
Figure 10
Conformational structures for the patuletin and RdRp at the first (A) and 100th (B) nanoseconds of the MD run.
Figure 11
Figure 11
MM-PBSA patuletin–amino acids of RdRp.
Figure 12
Figure 12
MM-PBSA patuletin–nucleotides of RdRp.
See this image and copyright information in PMC

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