Computer-Aided Analysis of Multiple SARS-CoV-2 Therapeutic Targets: Identification of Potent Molecules from African Medicinal Plants

Abstract

The COVID-19 pandemic, which started in Wuhan, China, has spread rapidly over the world with no known antiviral therapy or vaccine. Interestingly, traditional Chinese medicine helped in flattening the pandemic curve in China. In this study, molecules from African medicinal plants were analysed as potential candidates against multiple SARS-CoV-2 therapeutic targets. Sixty-five molecules from the ZINC database subset (AfroDb Natural Products) were virtually screened with some reported repurposed therapeutics against six SARS-CoV-2 and two human targets. Molecular docking, druglikeness, absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the best hits were further simulated. Of the 65 compounds, only three, namely, 3-galloylcatechin, proanthocyanidin B1, and luteolin 7-galactoside found in almond (Terminalia catappa), grape (Vitis vinifera), and common verbena (Verbena officinalis), were able to bind to all eight targets better than the reported repurposed drugs. The findings suggest these molecules may play a role as therapeutic leads in tackling this pandemic due to their multitarget activity.

Figure 1

2D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of PLpro. Hydrogen, carbon-hydrogen, and π bonds are depicted as green, light blue, and any other coloured (purple, magenta, orange, turquoise blue, pink, and yellow) lines, while Van der Waal interactions appear as light green circles.

Figure 2

3D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of PLpro.

Figure 3

2D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of 3CLpro. Hydrogen, carbon-hydrogen, and unfavourable and π bonds are depicted as green, light blue, red, and any other coloured (purple, magenta, orange, and pink) lines, while Van der Waal interactions appear as light green circles.

Figure 4

3D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of 3CLpro.

Figure 5

2D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of helicase. Hydrogen, carbon-hydrogen, and unfavourable and π bonds are depicted as green, light blue, red, and any other coloured (purple, magenta, orange, turquoise blue, pink, and yellow) lines, while Van der Waal interactions appear as light green circles.

Figure 6

3D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of helicase.

Figure 7

2D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of RdRp. Hydrogen, carbon-hydrogen, unfavourable, and π bonds are depicted as green, light blue, red, and any other coloured (purple, magenta, orange, turquoise blue, pink, and yellow) lines, while Van der Waal interactions appear as light green circles.

Figure 8

3D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of RdRp.

Figure 9

2D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of 2OMT. Hydrogen, carbon-hydrogen, unfavourable, and π bonds are depicted as green, light blue, red, and any other coloured (purple, magenta, orange, turquoise blue, pink, and yellow) lines, while Van der Waal interactions appear as light green circles.

Figure 10

3D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of 2OMT.

Figure 11

2D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of S-RBD. Hydrogen, unfavourable, and π bonds are depicted as green, red, and any other coloured (purple, magenta, orange, and pink) lines, while Van der Waal interactions appear as light green circles.

Figure 12

3D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of S-RBD.

Figure 13

2D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of ACE2. Hydrogen and π bonds are depicted as green and any other coloured (purple, magenta, orange, turquoise blue, pink, and yellow) lines, while Van der Waal interactions appear as light green circles.

Figure 14

3D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) chloroquine, (e) hydroxychloroquine, (f) lopinavir, (g) remdesivir, and (h) ritonavir in the binding pocket of ACE2.

Figure 15

2D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) camostat, (e) chloroquine, (f) hydroxychloroquine, and (g) nafamostat in the binding pocket of TMPRSS2. Hydrogen, carbon-hydrogen, and π bonds are depicted as green, light blue, and any other coloured (purple, magenta, orange, turquoise blue, pink, and yellow) broken lines, while Van der Waal interactions appear as light green circles.

Figure 16

3D representation of (a) 3-galloylcatechin, (b) proanthocyanidin B1, (c) luteolin 7-galactoside, (d) camostat, (e) chloroquine, (f) hydroxychloroquine, and (g) nafamostat in the binding pocket of TMPRSS2.