Structural and Biochemical Characterization of Novel Drug Targets from Pathogenic Organisms for the Development of Selective Inhibitors

Infectious diseases pose significant global challenges, acting as a leading cause of illness and death, particularly in low-income countries. Infectious diseases like lower respiratory infections, malaria, tuberculosis, and HIV/AIDS continue to cause millions of deaths annually, with vulnerable populations, especially young children in developing nations, being disproportionately affected. The overuse and misuse of antibiotics and other antimicrobial drugs are contributing to the emergence of drug-resistant pathogens, making common infections more difficult to treat and compromising the effectiveness of modern medicine. Addressing these complex challenges requires ongoing global collaboration, investment in resilient health systems, and proactive prevention strategies.

This Research Topic aims to address the urgent need for new therapeutic strategies against infectious diseases by focusing on the structural and biochemical characterization of novel drug targets from pathogenic organisms. The ultimate goal is to contribute to the development of a pipeline of novel, selective inhibitors that can effectively combat drug-resistant pathogens and provide new treatment options for infectious diseases.

This interdisciplinary Research Topic fosters the exchange of knowledge among scientists in drug discovery, integrating approaches from biochemistry, structural biology, and medicinal chemistry to combat infectious diseases and antimicrobial resistance. We welcome submissions that advance the development of novel, selective inhibitors for drug-resistant pathogens, encompassing (but not limited to) the following areas:

Target Identification and Validation: Identifying and validating essential proteins from pathogens that are crucial for their survival and virulence, and that exhibit significant differences from human homologs to ensure selectivity.

Protein Expression and Purification: Developing robust systems for the high-yield expression and purification of these novel drug targets, enabling detailed biochemical and structural studies.

Biochemical and Cell-Based Assay Development: Establishing and optimizing a suite of biochemical and cell-based assays for high-throughput screening of small molecule libraries to identify potential inhibitors.

Structural Elucidation: Determining the three-dimensional structures of these drug targets, both in their apo forms and in complex with lead compounds, using advanced techniques such as X-ray crystallography. This will provide critical insights into their active sites, substrate binding, and catalytic mechanisms.

Structure-Guided Inhibitor Design: Collaborating closely with medicinal chemistry teams to utilize structural information for the rational design and optimization of selective inhibitors. This will involve analyzing protein-ligand interactions to improve potency, selectivity, and pharmacokinetic properties.

Mechanism of Action Studies: Investigating the detailed mechanism of inhibition of lead compounds through enzyme kinetics, biophysical studies (e.g., ITC, SPR, thermal shift assays), and cellular assays.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Infectious Diseases, Drug Targets, Antimicrobial resistance, Structural Characterization, Selective Inhibitors, Structure-Guided Inhibitor Design

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.