In silico Analysis to Search for an Alternative Inhibitor of Biofilm Production by Helicobacter pylori

Antibiotic resistance is a growing concern in the current world. Regarding this, Helicobacter pylori is known to be present in the digestive tracts of human beings. In some people, the infection leads to stomach cancer. With the increasing problem of antibiotic resistance, reports show that drugs are no longer working with the same efficacy rate as they used to. The present work is a study of the two-component Acid-Response System (ArsRS) protein, one of the key proteins involved in biofilm formation by H. pylori.

In this study, an overall bioinformatics analysis was conducted of the bioactive compound, along with some FDA-approved drugs, to identify potential novel treatments for diseases associated with H. pylori. The molecular docking studies have been done with common drugs that are used for the treatment of the infection caused by H. pylori as Amoxicillin, Clarithromycin, Tetracycline, Levofloxacin, Metronidazole, Omeprazole, and Rabeprazole. Another aspect of the current study was to investigate the potential for national compounds such as Quercetin, α-mangostin, Phytol, Liquiritin, and D-mannitol as an alternative therapeutic agent. ADMET analysis and toxicity assessment were done to check the pharmacokinetics of the bioactive compounds. An in silico investigation of the H. pylori protein revealed its stability and compactness.

A higher number of intra-protein interactions increases the stability of H. pylori protein. Liquiritin emerged as an active molecule that can be used for inhibiting H. pylori biofilms. The FDAapproved drug Clarithromycin showed the highest binding energy among the synthetic group.

The target protein's structural and sequential analysis demonstrated how the correct number of amino acids boosts the protein's stability. The ability of bioactive chemicals to function as medications is indicated by their drug-likeness characteristics. According to toxicity evaluation, they do not have any serious effects when they come into contact with people through the environment. Liquiritin and Clarithromycin were the two top compounds that appeared as the best inhibitors.

Bioactive compounds that can be used as drugs. This work will also be beneficial for the development of synthetic drugs.