In Silico Drug Repurposing to Target Histone-Like Protein of Streptococcus Mutans

Abstract

Streptococcus mutans, in spite of its natural occurrence in human oral cavity, causes dental caries and rarely, in some complications, infective endocarditis. Development of vaccines or drugs to prevent or control these organisms has been under study. Histone-like protein (HLP), a nucleoid associated protein, is found essential for the survival and virulence of these pathogens. We have employed an in silico approach to specifically target the HLP of Streptococcus mutans with available approved drugs from DrugBank. Computational analysis showed conserved regions in DNA-binding domain of the S. mutans HLP and its homologues in 47-49 and 78-79 residues. The S. mutans HLP was found to be closely related within streptococcal species in phylogenetic analysis. Alanine and lysine were found to be higher in the protein which is the characteristic of histone-like proteins. The crystal structure of S. mutans HLP is similar to HLP from Mycobacterium tuberculosis despite their sequential variations and evolutionary distance. Etravirine, Abacavir, Adenosine phosphate, Flucloxacillin, Nelarabine, and Regadenoson were found to efficiently bind at the DNA binding domain of S. mutans HLP. From these results it can be concluded that these drugs can be repurposed to control streptococcal infections.