Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

Thiourea Derivatives Rejuvenate Dysfunctional Mitochondria in Chronic Hepatitis B Infection

Version 1 : Received: 19 May 2023 / Approved: 22 May 2023 / Online: 22 May 2023 (11:19:23 CEST)
Version 2 : Received: 27 May 2023 / Approved: 29 May 2023 / Online: 29 May 2023 (14:29:16 CEST)

A peer-reviewed article of this Preprint also exists.

Kumar, J., Tyagi, P., Singh, R., Saini, P., Sharma, D., & Maras, J. (2023). Thiourea Derivatives Restore Dysfunctional Mitochondria in Chronic Hepatitis B Infection. Reviewed, 11. https://doi.org/10.35248/0974-276X.23.16.652 Kumar, J., Tyagi, P., Singh, R., Saini, P., Sharma, D., & Maras, J. (2023). Thiourea Derivatives Restore Dysfunctional Mitochondria in Chronic Hepatitis B Infection. Reviewed, 11. https://doi.org/10.35248/0974-276X.23.16.652

Abstract

Chronic hepatitis B (CHB) infection and the Hepatitis B virus X protein (HBx) are major risk factors associated with hepatocellular carcinoma (HCC). In CHB infection, HBx induces mitochondrial dysfunction, exhaustion and impaired function in hepatocytes. Restoring hepatocyte health along with reduction in virus replication could be an ideal treatment for CHB. Thiourea derivatives are well known for their antiviral property though their effect on mitochondrial and/ or hepatocyte health remains obscure. This study focus on the repurposing of thiourea derivatives (DSA-00, DSA-02, and DSA-09) on hepatocyte replenishment. HepG2.2.15 cells were treated with thiourea derivatives, alongside Entecavir (ETV). The proteomics analysis showed both DSA-00 and ETV were enriched with proteins associated with antiviral responses. In addition, DSA-00 additionally showed increase in proteins linked to mitochondrial response. Whereas DSA-02 exhibited association with innate immune system and citric acid cycle and DSA-09 displayed pathways similar to DSA-00 and ETV. Treated groups exhibited enhanced bio-energetic and antiviral response as compared to the untreated group. FACS analysis revealed the restoration of exhausted hepatocytes by thiourea derivatives through targeting mitochondria. Our findings suggest that thiourea derivatives hold potential as a novel therapeutic agent that seems to restore mitochondrial health along with anti-viral response in CHB.

Keywords

Antiviral; Thiourea derivatives; Hepatitis B Virus; Chronic hepatitis B infection; Mitochondria dysfunction; Exhausted hepatocytes

Subject

Biology and Life Sciences, Virology

Comments (1)

Comment 1
Received: 29 May 2023
Commenter: Jitendra Kumar
Commenter's Conflict of Interests: Author
Comment: Chang the Title
Revised abstract 
revised result 
modifed the figure
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