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. 2022 Jun;40(9):4062-4072.
doi: 10.1080/07391102.2020.1852964. Epub 2020 Dec 15.

Multitarget in silico studies of Ocimum menthiifolium, family Lamiaceae against SARS-CoV-2 supported by molecular dynamics simulation

Amgad Albohy  1 , Eman Maher Zahran  2 , Usama Ramadan Abdelmohsen  2   3 , M Alaraby Salem  4 , Tarfah Al-Warhi  5 , Mohammad M Al-Sanea  6 , Narek Abelyan  7 , Hany Ezzat Khalil  8 , Samar Yehia Desoukey  3 , Mostafa Ahmed Fouad  3 , Mohamed Salah Kamel  2   3
Affiliations

Multitarget in silico studies of Ocimum menthiifolium, family Lamiaceae against SARS-CoV-2 supported by molecular dynamics simulation

Amgad Albohy et al. J Biomol Struct Dyn. 2022 Jun.

Abstract

The novel strain of human coronavirus, emerged in December 2019, which has been designated as SARS-CoV-2, causes a severe acute respiratory syndrome. Since then, it has arisen as a serious threat to the world public health. Since no approved vaccines or drugs has been found to efficiently stop the virulent spread of the virus, progressive inquiries targeting these viruses are urgently needed, especially those from plant sources. Metabolic profiling using LC-HR-ESI-MS of the butanol extract of Ocimum menthiifolium (Lamiaceae) aerial parts yielded 10 compounds including flavonoids, iridoids and phenolics. As it has been previously reported that some flavonoids can be used as anti-SARS drugs by targeting SARS-CoV-1 3CLpro, we chose to examine 14 flavonoids (detected by metabolomics and other compounds isolated via several chromatographic techniques). We investigated their potential binding interactions with the 4 main SARS-CoV-2 targets: Mpro, nsp16/nsp10 complex, ACE2-PD and RBD-S-protein via molecular docking. Docking results indicated that the nsp16/nsp10 complex has the best binding affinities where the strongest binding was detected with apigenin-7-O-rutinoside, prunin and acaciin with -9.4, -9.3 and -9.3 kcal/mol binding energy, respectively, compared to the control (SAM) with -8.2 kcal/mol. Furthermore, the stability of these complexes was studied using molecular dynamics of 150 ns, which were then compared to their complexes in the other three targets. MM-PBSA calculations suggested the high stability of acaciin-nsp16 complex with binding energy of -110 kJ/mol. This study sheds light on the structure-based design of natural flavonoids as anti-SARS-CoV-2 drugs targeting the nsp16/10 complex.Communicated by Ramaswamy H. Sarma.

Keywords: COVID-2; Ocimum menthiifolium; flavonoids; molecular docking; molecular dynamics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Isolated flavonoids docked against SARS-CoV-2.
Figure 2.
Figure 2.
(a) Validation of docking in the active site of nsp16 (6w4H). The figure shows very good overlapping between the crystalized (blue) and docked (pink) S-Adenosyl methionine (SAM). (b) 2D interactions of SAM in the active site of nsp16. (c) Overlapping of 9 with SAM in the active site of nsp16.
Figure 3.
Figure 3.
Docking of 9 (pink) takes place in the same groove that is taken by SAM (blue) in the active site of nsp16, compounds 11 and 14 binded at the same pocket. The nsp16/nsp10 complex in exposed where nsp16 is shown as green surface and nsp10 is shown as yellow cartoon.
Figure 4.
Figure 4.
Interactions of Compound 9 in the active site of SARS-CoV-2 nsp16 active site. (a) Compound 9 binding in the same SAM (natural ligand) groove. (b) 2D representation of the amino acids involved in the binding and recognition of compound 9 in the active site. (c) 3D representation of compound 9 interactions.
Figure 5.
Figure 5.
(a) Binding of compound 14 (blue) takes very similar position compared to 9 (green). Both compounds have very similar docking energies. (b) Binding of 11 (pink) is slightly different but maintain key interactions. anti-SARS-CoV-2 drugs targeting the nsp16/10 complex.
Figure 6.
Figure 6.
Compounds RMSD values during performed simulations.
See this image and copyright information in PMC

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