56 / 2024-10-23 16:59:30

De novo design and evaluation of novel protein inhibitors against Shiga toxin using artificial intelligence

The prevention and management of zoonotic diseases stand as a crucial pillar of the One Health approach. Shiga toxin-producing Escherichia coli (STEC) represents a significant zoonotic threat for public health. STEC infection can result in serious complications such as hemolytic uremic syndrome (HUS) in humans and edema in piglets, culminating in high mortality rates and substantial economic impact. Conventional antimicrobial remedies for STEC infections present a contentious issue, as antibiotic administration may exacerbate the production of the key virulence factor, Shiga toxin, thereby worsening outcomes. Hence, there is a pressing need for innovative therapeutic interventions to combat STEC infections effectively. This research employs artificial intelligence approaches to de novo design protein inhibitors targeting Shiga toxin 2a. Several protein binders were identified to bind to Shiga toxin 2a including one with very high affinity. The binders also showed neutralization activity against Shiga toxin 2a in a cell infection model. This study pioneers the design of protein binders against Shiga toxin 2a through artificial intelligence, offering promising prospects for the treatment of STEC infections and ultimately advancing the objectives of One Health.