Tomato leaf curl New Delhi virus (ToLCNDV) is a highly prevalent and destructive bipartite begomovirus that infects a wide range of plant species across three continents, raising global concerns. It is particularly prevalent in Asia but was identified in Africa in 2015, specifically in Tunisia, and in Mediterranean countries, specifically in Spain, in 2014. Moreover, Asian isolates are better adapted to tomato plants than Mediterranean isolates. In our initial analysis of ToLCNDV DNA-A sequences, it was observed that several Asian isolates have an additional open reading frame, referred to as AV3, whereas most of the Mediterranean isolates lack it. AV3 is the least characterized ORF that starts in the upstream region of AV2 and overlaps with it but in a different reading frame. To comprehend the potential role of AV3 protein in ToLCNDV infection, an in-silico study was conducted to investigate the interaction of AV2 and AV3 with Solanum lycopersicum-encoded RNA-dependent RNA polymerase 1 (RDR1). Both AV2 (112 amino acids in length) and AV3 (128 amino acids in length) proteins shared just 14 common amino acids, and their 3D structure showed the least resemblance. The results demonstrated that AV2 forms a more stable and robust binding with RDR1 compared to AV3. Nonetheless, the AV3-RDR1 complex had a higher binding energy (−59.64 kJ mol−1) and a smaller size (6 nm). The other proteinprotein interaction attributes inferred for the AV2-RDR1 and AV3-RDR1 complexes exhibited some fundamental similarities; however, the AV2-RDR1 complex showed better interacting/docking attributes than the AV3-RDR1 complex. Although AV2 and AV3 docked differentially to RDR1 at the same site, they both interacted with some common residues, including E825, D877, K880, K881, and E884. This suggests a shared pathway employed by both AV2 and AV3 to suppress host plant defense, or it may be a strategy of dual deception to evade host defense. Conclusively, this study revealed that AV3 exhibited a strong interaction with RDR1. So speculatively, AV3 may potentially establish a robust in vivo interaction with RDR1 to suppress host plant defense, providing speculative insights into why Asian isolates of ToLCNDV are better adapted to tomato plants than Mediterranean isolates.