Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.
Int J Mol Sci
; 24(9)2023 Apr 27.
Article
in English
| MEDLINE | ID: covidwho-2313623
ABSTRACT
Antiviral protease inhibitors are peptidomimetic molecules that block the active catalytic center of viral proteases and, thereby, prevent the cleavage of viral polyprotein precursors into maturation. They continue to be a key class of antiviral drugs that can be used either as boosters for other classes of antivirals or as major components of current regimens in therapies for the treatment of infections with human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, sustained/lifelong treatment with the drugs or drugs combined with other substance(s) often leads to severe hepatic side effects such as lipid abnormalities, insulin resistance, and hepatotoxicity. The underlying pathogenic mechanisms are not fully known and are under continuous investigation. This review focuses on the general as well as specific molecular mechanisms of the protease inhibitor-induced hepatotoxicity involving transporter proteins, apolipoprotein B, cytochrome P450 isozymes, insulin-receptor substrate 1, Akt/PKB signaling, lipogenic factors, UDP-glucuronosyltransferase, pregnane X receptor, hepatocyte nuclear factor 4α, reactive oxygen species, inflammatory cytokines, off-target proteases, and small GTPase Rab proteins related to ER-Golgi trafficking, organelle stress, and liver injury. Potential pharmaceutical/therapeutic solutions to antiviral drug-induced hepatic side effects are also discussed.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
HIV Infections
/
HIV Protease Inhibitors
/
Chemical and Drug Induced Liver Injury
/
COVID-19
Type of study:
Risk_factors_studies
Topics:
Long Covid
/
Vaccines
Limits:
Humans
Language:
English
Year:
2023
Document Type:
Article
Affiliation country:
Ijms24097938
Similar
MEDLINE
...
LILACS
LIS