The use of genomic variants to drive drug repurposing for chronic hepatitis B

Lalu Muhammad Irham; Wirawan Adikusuma; Dyah Aryani Perwitasari; Haafizah Dania; Rita Maliza; Imaniar Noor Faridah; Ichtiarini Nurullita Santri; Yohane Vincent Abero Phiri; Rockie Chong

doi:10.1016/j.bbrep.2022.101307

The use of genomic variants to drive drug repurposing for chronic hepatitis B

Biochem Biophys Rep. 2022 Jul 8:31:101307. doi: 10.1016/j.bbrep.2022.101307. eCollection 2022 Sep.

Authors

Lalu Muhammad Irham¹, Wirawan Adikusuma², Dyah Aryani Perwitasari¹, Haafizah Dania¹, Rita Maliza³, Imaniar Noor Faridah¹, Ichtiarini Nurullita Santri⁴, Yohane Vincent Abero Phiri^{5

6}, Rockie Chong⁷

Affiliations

¹ Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia.
² Departement of Pharmacy, University of Muhammadiyah Mataram, Mataram, Indonesia.
³ Biology Department, Faculty of Mathematics and Natural Sciences, Andalas University, Padang, West Sumatra, Indonesia.
⁴ Faculty of Public Health, Universitas Ahmad Dahlan, Yogyakarta, Indonesia.
⁵ School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan.
⁶ Institute for Health Research and Communication (IHRC), P.O Box 1958, Lilongwe, Malawi.
⁷ Department of Chemistry and Biochemistry, University of California, Los Angeles, USA.

Abstract

Background: One of the main challenges in personalized medicine is to establish and apply a large number of variants from genomic databases into clinical diagnostics and further facilitate genome-driven drug repurposing. By utilizing biological chronic hepatitis B infection (CHB) risk genes, our study proposed a systematic approach to use genomic variants to drive drug repurposing for CHB.

Method: The genomic variants were retrieved from the Genome-Wide Association Study (GWAS) and Phenome-Wide Association Study (PheWAS) databases. Then, the biological CHB risk genes crucial for CHB progression were prioritized based on the scoring system devised with five strict functional annotation criteria. A score of ≥ 2 were categorized as the biological CHB risk genes and further shed light on drug target genes for CHB treatments. Overlapping druggable targets were identified using two drug databases (DrugBank and Drug-Gene Interaction Database (DGIdb)).

Results: A total of 44 biological CHB risk genes were screened based on the scoring system from five functional annotation criteria. Interestingly, we found 6 druggable targets that overlapped with 18 drugs with status of undergoing clinical trials for CHB, and 9 druggable targets that overlapped with 20 drugs undergoing preclinical investigations for CHB. Eight druggable targets were identified, overlapping with 25 drugs that can potentially be repurposed for CHB. Notably, CD40 and HLA-DPB1 were identified as promising targets for CHB drug repurposing based on the target scores.

Conclusion: Through the integration of genomic variants and a bioinformatic approach, our findings suggested the plausibility of CHB genomic variant-driven drug repurposing for CHB.

Keywords: Bioinformatics; Chronic hepatitis B; Drug repurposing; Genomic variants.