In-silico screening of bioactive compounds from nut grass (Cyperus rotundus) to inhibit the α-bungarotoxin from Kraits (Bungarus spp.) venom

Figures & data

Table 1. Vina search space used in this study.

Grid	Axis
	X	Y	Z
Centre	8.2022	2.8887	1.4352
Dimensions (Angstrom)	20.2814	18.1712	13.4120

Table 2. The 19 bioactive compounds that had drug-like characteristics, sorted by their log P_o/w..

Bioactive compound	PubChem Id	Formula	Molecular Weight (g/mol)	No. of H-Bond Donors	No. of H-Bond Acceptors	Lipophilicity (Consensus Log Po/w)
Alpha-Cyperone	6452086	C15H22O	218.33	0	1	3.69
Cyperol	14076601	C15H24O	220.35	1	1	3.49
Cyperusol B2	11310916	C15H24O2	236.35	1	2	3.15
Rotundine B	21603505	C15H23NO	233.35	1	2	3.07
Rotundine A	10728239	C15H21NO	231.33	0	2	3.04
4,6,3’,4’ Tetramethoxyaurone	11186921	C19H18O6	342.34	0	6	3.01
4,7-Dimethyl −1-tetralone	5316902	C12H14O	174.24	0	1	2.85
Beta rotunol	5321005	C15H22O2	234.33	1	2	2.77
6,3‘, 4’- Trihydroxy-4-methoxy-5-methylaurone	42607777	C17H14O6	314.29	3	6	2.25
Cyperusol D	11311311	C15H24O3	252.35	3	2	2.16
Apigenin	5280443	C15H10O5	270.24	3	5	2.11
Scaberin	42608130	C19H18O7	358.34	1	7	1.92
Cyperusol A1	10083471	C15H22O3	250.33	2	3	1.9
Sulfuretin	5281295	C15H10O5	270.24	3	5	1.9
Luteolin	5280445	C15H10O6	286.24	4	6	1.73
Aureusidin	5281220	C15H10O6	286.24	4	6	1.72
p-Coumaric acid	637542	C9H8O3	164.16	2	3	1.26
Quercetin	5280343	C15H10O7	302.24	5	7	1.23
4-Hydroxybenzoic acid	135	C7H6O3	138.12	2	3	1.05

Table 3. Pharmacokinetics and metabolism prediction of bioactive compounds.

No	Bioactive compound	Blood-brain barrier permeability	Gastrointestinal tract absorbance
1	Alpha-Cyperone	Yes	High
2	Cyperol	Yes	High
3	Cyperusol B2	Yes	High
4	Rotundine B	Yes	High
5	Rotundine A	Yes	High
6	4,6,3’,4’ Tetramethoxyaurone	Yes	High

Figure 1. The toxicity evaluation and membrane permeability prediction of six potential compounds. a) Toxicity classification based on toxicity class and LD50. b) The probability of inducing several kinds of toxicity. c) The membrane permeability prediction of six bioactive compounds (top) with the energy required to pass the phospholipid membrane (bottom).

Figure 2. The visualization of molecular docking between α-bungarotoxin (cyan) with a) Alpha-cyperone, b) Cyperol, c) Cyperusol B2, d) Rotundine a, e) Rotundine b, f) 4,6,3’,4’-tetramethoxyaurone, g) Anti-α-bungarotoxin peptide. Dashed lines represent interaction type, with the dark and light green lines representing hydrogen bonds and the pink line representing hydrophobic interaction.

Table 4. Detailed interactions between α-bungarotoxin with bioactive compounds and inhibitor control.

Protein	Bioactive compound	Binding affinity (Kcal/mol)	Interaction	Amino acid residues
α-bungarotoxin	anti-α-bungarotoxin peptide	−3.8	Hydrogen bond	THR6 PRO10 ILE11 SER35 ARG36 LYS38
			Hydrophobic	–
	Alpha-cyperone	−5.1	Hydrogen bond	ARG36
			Hydrophobic	LYS38 VAL40 HIS68 PRO69 LYS70
	Cyperol	−5.5	Hydrogen bond	–
			Hydrophobic	LYS38 VAL40 HIS68 PRO69 LYS70
	Cyperusol B2	−4.8	Hydrogen bond	ASP30 GLY37 HIS68
			Hydrophobic	LYS38 LYS70
	Rotundine A	−5.0	Hydrogen bond	–
			Hydrophobic	LYS70
	Rotundine B	−5.1	Hydrogen bond	ASP30 GLY37
			Hydrophobic	LYS70
	Tetramethoxyaurone	−6.0	Hydrogen bond	THR6 SER35 ARG36 VAL40 HIS68
			Hydrophobic	VAL40

Figure 3. The RMSD (a), Radius of gyration (b), Number of Hydrogen Bond (c), Surface area (d), and RMSF (e) Calculation for α-bungarotoxin and bioactive compound complexes after 20 nanoseconds of simulation. αbtx-acypn: α-bungarotoxin- alpha-cyperone, αbtx-cyprl: α-bungarotoxin-cyperol, αbtx-cypB2: α-bungarotoxin-cyperusol B2, αbtx-rtdA: α-bungarotoxin-rotundine A, αbtx-rtdB: α-bungarotoxin-rotundine B, αbtx-ttrx: α-bungarotoxin-4,6,3’,4’-tetramethoxyaurone.