Gene Interaction Network Analysis Reveals IFI44L as a Drug Target in Rheumatoid Arthritis and Periodontitis
Pradeep Kumar Yadalam,
Thilagar Sivasankari,
Santhiya Rengaraj,
Maryam H. Mugri,
Mohammed Sayed,
Samar Saeed Khan,
Mona Awad Kamil,
Shilpa Bhandi,
A. Thirumal Raj,
Shankargouda Patil,
Artak Heboyan
Affiliations
Pradeep Kumar Yadalam
Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, India
Thilagar Sivasankari
Department of Periodontology, Adhiparasakthi Dental College and Hospital, Melmaruvathur 603319, India
Santhiya Rengaraj
Department of Periodontology, Adhiparasakthi Dental College and Hospital, Melmaruvathur 603319, India
Maryam H. Mugri
Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia
Mohammed Sayed
Department of Prosthetic Dental Sciences, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia
Samar Saeed Khan
Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45142, Saudi Arabia
Mona Awad Kamil
Department of Preventive Dental Science, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia
Shilpa Bhandi
Department of Restorative Dental Science, College of Dentistry, Jazan University, Jazan 45142, Saudi Arabia
A. Thirumal Raj
Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Chennai 600130, India
Shankargouda Patil
Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45142, Saudi Arabia
Artak Heboyan
Department of Prosthodontics, Faculty of Stomatology, Yerevan State Medical University after Mkhitar Heratsi, Str. Koryun 2, Yerevan 0025, Armenia
Objective: Despite extensive research on periodontitis and rheumatoid arthritis, the underlying molecular connectivity between these condition remains largely unknown. This research aimed to integrate periodontitis and rheumatoid arthritis gene expression profiles to identify interconnecting genes and focus to develop a common lead molecule against these inflammatory conditions. Materials and Methods: Differentially expressed genes (DEGs) of periodontitis and rheumatoid arthritis were identified from the datasets retrieved from the Gene Expression Omnibus database. The network was constructed by merging DEGs, and the interconnecting genes were identified and ranked using GeneMANIA. For the selected top ranked gene, the potential inhibitor was searched using FINDSITEcomb2.0. Subsequently, the molecular docking and molecular dynamics were performed to determine the binding efficiency and protein-ligand complex stability, respectively. Results: From the network analysis, IFN-induced protein 44-like (IFI44L) was identified as a top ranked gene involved in most of the immunological pathway. With further virtual screening of 6507 molecules, vemurafenib was identified to be the best fit against the IFI44L target. The binding energy and stability of IFI44L with vemurafenib were investigated using molecular docking and molecular dynamics simulation. Docking results show binding energy of −7.7 Kcal/mol, and the simulation results show stability till 100 ns. Conclusions: The identified IFI44L may represent a common drug target for periodontitis and rheumatoid arthritis. Vemurafenib could be a potent anti-inflammatory drug for both diseases.
