Volume 25, Issue 111, May, 2021

Identification of novel leads against Cystalysin of Treponema denticola to combat Periodontitis: A computational approach

Mahvish Khan¹, Saif Khan^2♦, Khurshid Ahmad³, Mohtashim Lohani⁴, Shafiul Haque⁵, Hazza A Alhobeira⁶, Ammar A Siddiqui⁷, Shadab Mirza⁸, Arshad Hussain⁹

¹Department of Biology, College of Science, University of Ha’il, Ha’il2440, KSA ²Department of Basic Dental and Medical Sciences, College of Dentistry, University of Ha’il, Ha’il-2440, KSA
³Department of Medical Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea
⁴Department of Emergency Medical Services, Faculty of Applied Medical Sciences, Jazan University, Jazan-45142, KSA
⁵Research and Scientific Studies, Unit, College of Nursing & Allied Health Sciences, Jazan University, Jazan-45142, KSA
⁶Department of Restorative Dentistry, College of Dentistry, University of Ha’il, Ha’il-2440, KSA
⁷Department of Preventive Dentistry, College of Dentistry, University of Ha’il, Ha’il-2440, KSA
⁸Department of Clinical Administration, College of Dentistry, University of Ha’il, Ha’il-2440, KSA
⁹Clinical Pharmacy Department, College of Pharmacy, University of Ha’il, Ha’il-2440, KSA

^♦Corresponding author
Department of Basic Dental and Medical sciences, College of Dentistry, Hail University, Hail, Saudi Arabia

ABSTRACT

Present study attempts to determine efficient biogenic leads against proteolytic enzyme Cystalysin of Treponema denticola, a red complex pathogen, responsible for periodontitis. Cystalysin is known to play central role in the occurrence and progression of chronic generalized periodontitis. The method involves the preparation of library of compounds having biogenic origin from a large database of known compounds (ZINC). High throughput screening of 308035 compounds in the biogenic library was done to determine the top 100 best inhibitors depending on their binding efficiency. Top five Inhibitors were then subjected to exhaustive docking refinement to characterize the type and degree of interactions. Top inhibitors were found to undergo multiple hydrogen bonding and pi-anion interactions with active site residues critically important for the proteolytic activity of the enzyme. These inhibitors efficiently block the proteolysis due to Cystalysin and hence restrict the progression of periodontitis. Favorable ADMET properties of these ligands approve them to be used as potential drug like molecules against periodontal infections.

Keywords: Periodontitis, Cystalysin, Treponema, Drug discovery

Medical Science, 2021, 25(111), 1111-1116

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