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

ABSTRACT

Kraits (Bungarus spp.) are the snakes that commonly cause fatal bites in Tropical Asia due to their neurotoxic venom. The complex process of antivenom production contributes to the lack of available antivenom and amplifies the burden of snakebite in that region. Thus, the victims seek traditional medicine such as root extract from nut grass (Cyperus rotundus). In the present study, we utilized bioinformatics methods to analyze the potential inhibitory activity of bioactive compounds from nut grass (Cyperus rotundus) against kraits’ α-bungarotoxin. Twenty-one bioactive compounds were screened using ADMET, membrane permeability prediction, molecular docking and molecular dynamics simulations. Among these bioactive compounds, we found that alpha-cyperone, cyperol, cyperusol, rotundine A, rotundine B and 4,6,3’,4’-Tetramethoxyaurone had inhibitory activity by presenting a good ability to pass phospholipid bilayer and could bind stably into active sites of α-bungarotoxin with minimum energy required. Importantly, the neutralization property of these bioactive compounds resides in their combinational function, underscoring the crucial significance of their combined action rather than individual contributions. In conclusion, this study identifies a combination of six bioactive compounds from C. rotundus with a potential as an alternative antivenom based on in-silico screening and provides essential data for the development of a plant-based antivenom.

KEYWORDS:

• α-bungarotoxin
• antivenom alternative
• Cyperus rotundus
• snakebite
• terpenes
• traditional medicine

Abbreviations

3FTX:	=	three-finger toxin
PLA2:	=	phospholipase A2
nAChR:	=	neuronal nicotinic acetylcholine receptor
RMSD:	=	root-mean-square deviations
Rg:	=	radius of gyration
RMSF:	=	RMS fluctuation
SASA:	=	three-finger toxin

Acknowledgments

We are grateful to Feri Eko Hermanto for assisting molecular dynamics simulation and providing the early review of this manuscript.

Disclosure statement

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

Authors’ contributions

RG: Conceptualisation, Formal analysis, Investigation, Writing – Original Draft. MHW: Formal analysis, Methodology, Writing – Original Draft. SR: Supervision, Writing – review & editing. MR: Supervision, Writing – review & editing. NW: Conceptualisation, Resources, Supervision, Writing – review & editing.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.