Targeting Antimicrobial-Resistant Diarrhea: Pathogen-Specific and Anti-Virulence Drug Discovery via Molecular Docking

Abstract

Infectious diarrhea is an increasing global healthcare issue due to the cause of mortality among children under five caused by pathogens such as bacteria, viruses, and parasites. The increasing prevalence of antimicrobial resistance (AMR) has further complicated treatment efforts, highlighting an urgent need for the development of novel therapeutic agents. Antimicrobial chemotherapeutics are often hindered by issues such as gut microbiome disruption and the rising incidence of resistance, highlighting the necessity for pathogen-specific and anti-virulence drug development. This review investigates the wider landscape of AMR-associated diarrhea, focusing on the resistance mechanisms of key pathogens such as Clostridioides difficile and Shigella. It highlights the potential of in silico molecular docking studies as a powerful and efficient computational tool in the drug discovery process by means of accuracy and pathogen-specific drug development. Molecular docking strategies, through profiling ligand-target interactions according to their binding affinity, can help to design promising drug candidates and elucidate their mechanisms of action. Recent studies have shown that the computational docking in screening for inhibitors against drug-resistant targets, paving the way for anti-virulence drug discovery and drug repurposing. This review discusses how some of prospective strategies used by emphasizing the in silico molecular docking methodologies to expedite the development of novel anti-diarrheal drugs with antimicrobial properties. This review outlines how specific AMR targets derived from different microorganisms can be considered as targets for anti-virulence drug development in the context of infectious diarrhea. Therefore, molecular docking approaches could represent a significant advance in combating the growing threat of AMR as a concept.

Keywords

• antimicrobial resistance (AMR)
• AMR-associated diarrhea
• infectious diarrhea
• molecular docking
• symptom-driven drug development
• in silico

Supporting Institution

Republic of Turkey Ministry of National Education (MEB)

Ethical Statement

This article is a review study and does not contain any experimental research on human participants or animals performed by the author(s). Therefore, ethics committee approval is not required.

Thanks

The corresponding author is grateful to the Republic of Turkey Ministry of National Education (MEB) for the financial support provided through the YLSY scholarship program.

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