In Silico Investigation of the Interactions Between Cotton Leaf Curl Multan Virus Proteins and the Transcriptional Gene Silencing Factors of Gossypium hirsutum L

The highly dynamic nature of the Cotton leaf curl virus (CLCuV) complex (causing Cotton leaf curl disease, a significant global threat to cotton) presents a formidable challenge in unraveling precise molecular mechanisms governing viral-host interactions. To address this challenge, the present study investigated the molecular interactions of 6 viral proteins (Rep, TrAP, C4, C5, V2, and βC1) with 18 cotton Transcriptional Gene Silencing (TGS) proteins. Protein–protein dockings conducted for different viral-host protein pairs using Clustered Protein Docking (ClusPro) and Global RAnge Molecular Matching (GRAMM) (216 docking runs), revealed variable binding energies. The interacting pairs with the highest binding affinities were further scrutinized using bioCOmplexes COntact MAPS ( COCOMAPS) server, which revealed robust binding of three viral proteins- TrAP, C4, and C5 with 14 TGS proteins, identifying several novel interactions (not reported yet by earlier studies), such as TrAP targeting DCL3, HDA6, and SUVH6; C4 targeting RAV2, CMT2, and DMT1; and C5 targeting CLSY1, RDR1, RDR2, AGO4, SAMS, and SAHH. Visualizing these interactions in PyMol provided a detailed insight into interacting regions. Further assessment of the impact of 18 variants of the C4 protein on interaction with CMT2 revealed no correlation between sequence variation and docking energies. However, conserved residues in the C4 binding regions emerged as potential targets for disrupting viral integrity. Hence, this study provides valuable insights into the viral-host interplay, advancing our understanding of Cotton leaf curl Multan virus pathogenicity and opening novel avenues for devising various antiviral strategies by targeting the host-viral interacting regions after experimental validation.