Computational analysis to determine the potential antiviral candidates against Cotton leaf curl Kokhran virus (CLCuKoV)

Abstract

Begomoviruses are circular, single-stranded DNA (ssDNA) viruses that can have either a monopartite or bipartite genome. They belong to family Geminiviridae. These small viral gnomes, containing four to six open reading frames (ORFs), are economically crucial due to their association with a number of plant diseases, specially Cotton leaf curl disease (CLCuD). Bemisia tabaci, a highly polyphagous white fly that is involved in causing the transmission of these viruses as well as infecting hundreds of other plants species as well. In this study, in silicon methods are employed to analyse potential anti-viral compounds and anti-viral protein against Cotton leaf curl Kokhran virus (CLCuKoV). Structures for all seven viral proteins and eight out of fourteen anti-viral proteins were successfully modelled by using homology modelling, threading and ab initial approaches. The produced models were validated on the basis of C-score, TM-score and RMSD. The most suitable models were simulated by GROMACS to determine their structural stability. Following this, nighty eight viral protein anti-viral protein interactions were analysed using HDOCK web server. The results indicated significant interactions particularly between Rep and CP with anti-viral protein Tomato Tm-1 along with the docking score of -303.33 and -301.76. The interacting residues were further evaluated by PYMOL. In parallel structures for five anti-viral compounds were generated through openbabel, followed by ADMET analysis using SwissADME. Using AutoDock vina software, viral proteins were docked against anti-viral proteins, resulting in thirty-five interactions. Specifically, Rep protein displayed the highest binding affinity with anti-viral compound Bruceine D, with the docking score of -9.2 kcal/mol. The interaction residues for protein compound complexes were determined by using discovery studio. The findings highlight the mechanism of anti-viral approach that will ultimately aid in the development of effective control strategies.