A computational approach to fighting type 1 diabetes by targeting 2C Coxsackie B virus protein with flavonoids

Area of Science:

• Biochemistry
• Virology
• Pharmacology

Background:

• Type 1 diabetes (T1D) is an autoimmune condition characterized by insufficient insulin production due to pancreatic cell destruction, leading to hyperglycemia.
• Pathogenicity of T1D involves a complex interplay of immune responses, genetic predisposition, and environmental factors.
• Coxsackie B4 viruses are implicated as a potential environmental trigger for T1D.

Purpose of the Study:

• To identify and evaluate flavonoids as potential therapeutic agents against Coxsackie virus proteins implicated in type 1 diabetes.
• To computationally screen flavonoids for their ability to inhibit viral targets relevant to T1D pathogenesis.

Main Methods:

• Protein target identification and molecular docking of flavonoids against the selected viral protein (1z8r).
• ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) analysis and molecular dynamics simulations (300 ns) to assess compound stability and interactions.
• Post-simulation analyses including RMSD, RMSF, secondary structure analysis, and MM-GBSA calculations to evaluate binding affinity.

Main Results:

• A lead compound, CID_5280445, was identified based on favorable docking scores and ADMET profiles.
• The selected compound demonstrated non-toxic properties and met Blood-Brain Barrier (BBB) likeness criteria.
• Molecular dynamics simulations and binding energy calculations confirmed strong interaction between CID_5280445 and the viral target.

Conclusions:

• CID_5280445 emerged as a promising non-toxic candidate for further investigation as a treatment for Coxsackie virus-induced type 1 diabetes.
• This study provides a computational foundation for developing novel antiviral therapies targeting T1D.
• Findings offer insights into potential chemical interventions against viruses associated with autoimmune diabetes.