Targeting Fks1 proteins for novel antifungal drug discovery

• Published in: Trends in pharmacological sciences (Regular ed.) Vol. 45; no. 4; pp. 366 - 384
• Main Authors: Kumar, Vinit, Huang, Juan, Dong, Yawen, Hao, Ge-Fei
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2024
• Subjects: Antifungal Agents - pharmacology; antifungal drug target; Drug Discovery; Echinocandins; Fks1; fungal cell wall; fungal infections; Humans; ibrexafungerp; β-1,3-glucan synthase; ibrexafungerp; Fks1; echinocandins; β-1,3-glucan synthase; fungal cell wall; antifungal drug target; fungal infections
• ISSN: 0165-6147; 1873-3735
• DOI: 10.1016/j.tips.2024.02.007

Fks1 is a unique enzyme that makes β-1,3-glucan, a key cell wall component. Blocking Fks1 kills fungi by damaging their cell wall.Fks1 enhances fungal virulence and host infection by contributing to pathogenesis and immune response, while β-1,3-glucan is a biomarker for fungal infections.Fks1 is a promising target for new antifungal drugs. Studies on echinocandins and ibrexafungerp have identified their binding sites and action mechanisms on Fks1.Improvements in existing drugs can increase their antifungal activity.Fks1 research is essential to develop better antifungal drugs. More studies on Fks1 are needed to understand its structure, function, and interaction with antifungal agents crucial for drug optimization and design. Fungal infections are a major threat to human health. The limited availability of antifungal drugs, the emergence of drug resistance, and a growing susceptible population highlight the critical need for novel antifungal agents. The enzymes involved in fungal cell wall synthesis offer potential targets for antifungal drug development. Recent studies have enhanced our focus on the enzyme Fks1, which synthesizes β-1,3-glucan, a critical component of the cell wall. These studies provide a deeper understanding of Fks1’s function in cell wall biosynthesis, pathogenicity, structural biology, evolutionary conservation across fungi, and interaction with current antifungal drugs. Here, we discuss the role of Fks1 in the survival and adaptation of fungi, guided by insights from evolutionary and structural analyses. Furthermore, we delve into the dynamics of Fks1 modulation with novel antifungal strategies and assess its potential as an antifungal drug target. Fungal infections are a major threat to human health. The limited availability of antifungal drugs, the emergence of drug resistance, and a growing susceptible population highlight the critical need for novel antifungal agents. The enzymes involved in fungal cell wall synthesis offer potential targets for antifungal drug development. Recent studies have enhanced our focus on the enzyme Fks1, which synthesizes β-1,3-glucan, a critical component of the cell wall. These studies provide a deeper understanding of Fks1’s function in cell wall biosynthesis, pathogenicity, structural biology, evolutionary conservation across fungi, and interaction with current antifungal drugs. Here, we discuss the role of Fks1 in the survival and adaptation of fungi, guided by insights from evolutionary and structural analyses. Furthermore, we delve into the dynamics of Fks1 modulation with novel antifungal strategies and assess its potential as an antifungal drug target.