Cotton (Gossypium spp.), popularly known as 'White Gold', is one of the world's most valuable commercial fibre and oil crop. It has a dominating role in the industrial and agricultural economy. In India, it plays important role in the national economy and employs more than eight million people. The main bottleneck in cotton cultivation is the yield losses due to biotic stresses like insect-pests’ attack, diseases, and crop-weed competition. Major insect-pests of cotton include bollworms, foliage feeders and sucking pests, which cause serious damage to different parts of the plant all through the cropping season. With the introduction of Bt cultivars of cotton having resistance against cotton bollworms, sucking pests especially the whitefly, have emerged as serious problems (https://atariz1.icar.gov.in/pdf/Report-KVKs-at-Farmers-Doorsteps.pdf).
The whitefly (Bemisia tabaci Gennadius) is homopteran insect belonging to family Aleyrodidae. It is a polyphagous insect that feeds on more than 500 plant species including field crops, vegetables, fruits, oil seed crops, ornamental plants, etc. It is a highly destructive pest that causes huge economic losses every year by reducing crops yields and quality. This pest also acts as a vector for several viral pathogens in cultivated plants (Byrne 1990; Schuster et al. 1995; Oetting and Buntin 1996; Kumar et al. 2020).
On cotton crop, the damage caused by whitefly is due to direct feeding and through lint contamination by the development of sooty mould honeydew on its execrate (Kedar et al. 2014). The whitefly is also the vector of Cotton leaf curl virus (CLCuV). Due to lack of effective genetic resistance, farmers occasionally had to rely on insecticides for efficient management of whitefly. However, in certain situations, highly effective integrated pest management (IPM) strategy has been developed, disseminated and ensured its adoption that has given effective control of the pest. Supervised use of chemical insecticides using economic threshold level (ETL) is one component under IPM (Kumar et al. 2020).
Several insecticides are approved and recommended for this pest but B. tabaci has enormous potential to develop resistance against the insecticides. Besides, these chemical insecticides are also hazardous for the environment and injurious to other non-target living organisms (Kumar et al. 2020). So there is need to search for natural molecules with novel selective insecticidal action against B. tabaci.
In whitefly and other arthropods, the external cuticle is rigid and inexpansible. Therefore, these animals have evolved a moulting process that facilitates growth and required morphological changes. To enable the co-ordination of growth with environmental signals, moulting is under the regulation of steroid hormones like the ecdysteroids -a-ecdysone (aE) and its biologically active form, 20-hydroxy ecdysone (20-E). Receptor for ecdysone, the Ecdysone Receptor (EcR) regulates larval moulting, metamorphosis and reproduction (Auwerx et al. 1999; Riddiford et al. 2000).
Ecdysone receptor is a Ligand-dependent transcription factor which belongs to the superfamily of Nuclear Receptors (Koelle et al. 1991; Mangelsdorf et al. 1995; Freedman 1997). Ecdysone receptor is found only in invertebrates and serves as a key regulator of the gene expression during the development and reproduction of most invertebrates (Riddiford et al. 2000). The functional unit of the receptor is a noncovalent heterodimeric complex of two proteins Ecdysone Receptor (EcR) and another nuclear receptor family member, Ultraspiracle Protein (USP) (Auwerx et al. 1999; Yao et al. 1992; 1993; de Oliveira et al. 2019). EcR and USP have a similar modular domain structure as that of all other nuclear receptors, constituting a well-conserved DNA binding domain (DBD) and a somewhat conserved ligand-binding domain (LBD) (Koelle et al. 1991). The Ecdysone binding site is present in the LBD of the EcR subunit, but USP must be dimerised with EcR for high-affinity binding of ligand. EcRs heterodimerize with USPs to attain transcriptional activity in the presence of ecdysteroids (Nakagawa et al. 2009). Based on literature study as its role in pathophysiology, it can be used as a potential target for the identification of environmentally safe insecticides to specifically obstruct the molting process of insects, thus controlling insect damage.
Recognition of compounds that can act as significant inhibitors of target pathogenic/insect proteins, specific to that pest and optimization of these inhibitors to enhance their affinity, efficiency, selectivity, bioavailability, and metabolic stability are the steps involved in the modern drug/agrochemical discovery programme.
High-throughput screening (HTS) is a tedious process due to the availability of a large number of compounds (Shukla et al. 2018). Therefore, a faster equivalent i.e. structure-based virtual screening can be used for screening of potential inhibitors that can interact with EcR receptor of B. tabaci and obstruct its development and reproduction process. In our study, we have performed structure based virtual screening, molecular dynamics simulation (MDS), and binding free energy analysis of natural compounds available at the ZINC database to identify potential inhibitors against Bemisia tabaci EcR (Irwin et al. 2012).