Screening Marine Microbial Metabolites as Promising Inhibitors of Borrelia garinii : A Structural Docking Approach towards Developing Novel Lyme Disease Treatment.

Lyme disease caused by the Borrelia species is a growing health concern in many parts of the world. Current treatments for the disease may have side effects, and there is also a need for new therapies that can selectively target the bacteria. Pathogens responsible for Lyme disease include B. burgdorferi , B. afzelii , and B. garinii . In this study, we employed structural docking-based screening to identify potential lead-like inhibitors against the bacterium. We first identified the core essential genome fraction of the bacterium, using 37 strains. Later, we screened a library of lead-like marine microbial metabolites ( n = 4730) against the arginine deiminase (ADI) protein of Borrelia garinii . This protein plays a crucial role in the survival of the bacteria, and inhibiting it can kill the bacterium. The prioritized lead compounds demonstrating favorable binding energies and interactions with the active site of ADI were then evaluated for their drug-like and pharmacokinetic parameters to assess their suitability for development as drugs. Results from molecular dynamics simulation (100 ns) and other scoring parameters suggest that the compound CMNPD18759 (common name: aureobasidin; IUPAC name: 2-[(4 R ,6 R )-4,6-dihydroxydecanoyl]oxypropan-2-yl (3 S ,5 R )-3,5-dihydroxydecanoate) holds promise as a potential drug candidate for the treatment of Lyme disease, caused by B. garinii . However, further experimental studies are needed to validate the efficacy and safety of this compound in vivo .