Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Thiourea Derivatives Rejuvenate Mitochondria and Provide Anti-viral Activity Against Chronic Hepatitis B Infection

Jitendra Kumar
* ORCID logo ,
Purnima Tyagi
ORCID logo ,
Akhilesh Kumar Saini
,
Deepti Sharma
,
Jaswinder Singh Maras
* ,
Vijay Kumar
*
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 protein X (HBx) are a major risk factor for the development of hepatocellular carcinoma (HCC). In CHB, HBx induces mitochondrial dysfunction, exhaustion and impaired function in hepatocytes. Restoring hepatocyte health along with reduction in virus replication could be an ideal treatment of CHB. Thiourea derivatives are well known for their antiviral property though their effect on mitochondrial and/ or hepatocyte health is obscure. The current pilot study focus on the repurposing of DSA-00, DSA-02, and DSA-09 on mitochondrial health and hepatocyte replenishment. HepG2.2.15 cells were treated with these, alongside Entecavir (ETV). The proteomics analysis showed DSA-00 and ETV were enriched with proteins associated with antiviral responses. DSA-00 additionally showed increase in proteins linked to mitochondrial response. DSA-02 showed association with innate immune system and citric acid cycle. DSA-09 displayed pathways similar to DSA-00 and ETV. The treated groups exhibited enhanced bio-energetic and antiviral response compared to the untreated group. FACS analysis, validated thiourea derivatives restored exhausted hepatocytes by targeting mitochondrial potential and function. Our findings suggest that (DSA-00, DSA-02, and DSA-09) may hold potential as a novel treatment strategy restoring mitochondrial healthy along with anti-viral response in CHB.

Keywords

Thiourea derivatives; Hepatitis B Virus; Hepatitis B Virus X protein; Mitochondria Dysfunctions; Exhausted Hepatocytes

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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