In silico identification of a promising inhibitor of Fusarium oxysporum f. sp. Lycopersici, Secreted in Xylem 1 protein.

Fusarium oxysporum f. sp. Lycopersici (FOL) is a soilborne pathogen that infects tomato plants and inflicts severe damage, resulting in heavy yield losses worldwide, causing Fusarium wilt disease. FOL encodes several pathogenicity factors necessary for colonizing and invading the host plants. Secreted in Xylem (SIX), a pathogenicity factor, is a small cysteine-rich fungal protein found in the xylem sap of FOL-infected tomato plants, which plays a major role in determining host specificity and in contributing to pathogenicity/virulence. However, the structure of SIX1 has not been modeled yet. Therefore, this study aimed to elucidate the structure of SIX1 by comparative modeling using Robetta server. The best possible structures obtained were then refined, validated, and utilized for subsequent analysis. An antifungal library comprising 16,824 compounds was screened to determine small molecules that can interact with SIX1. Five antifungal compounds were identified from the library. Further analyses revealed that, of the five ligands, 4-[(2-(3-methoxyphenoxy)acetyl)amino] benzamide exhibited the capacity to stably interact with SIX1. This shows that 4-[[2-(3-methoxyphenoxy)acetyl]amino] benzamide can be used as a potential candidate in the prevention of FOL infection. In summary, small-molecule inhibitors such as 4-[[2-(3-methoxyphenoxy)acetyl]amino] benzamide could be highly effective in combating FOL infection, along with biocontrol methods and strategies that use transgenic plants overexpressing resistance genes.