Human endogenous retrovirus K protease (HERV-K PR)

Human endogenous retrovirus K (HERV-K) protease is an aspartic protease encoded by the pol gene of the HML-2 subfamily, which represents the most recently integrated and biologically active endogenous retroviruses in the human genome (UniProt: P10266). While typically silenced in healthy tissues, HERV-K is frequently reactivated in various cancers, such as melanoma and breast cancer, as well as in neurodegenerative conditions like Amyotrophic Lateral Sclerosis (ALS) (PubMed: 26416744, 30104378). The protease is essential for the retroviral life cycle, as it cleaves the Gag and Gag-Pol polyproteins into mature, functional components required for viral particle assembly and infectivity (PubMed: 17604210). In the context of ALS, the expression of HERV-K proteins is hypothesized to contribute to motor neuron toxicity, making the protease a viable target for therapeutic intervention. Studies have shown that several HIV-1 protease inhibitors, including darunavir and lopinavir, can inhibit HERV-K protease activity, suggesting a potential for drug repurposing (PubMed: 29438182). Targeting this enzyme aims to suppress the production of pathogenic viral proteins and mitigate the progression of associated diseases.

Other names

HERV-K102 proteaseHERV-K(HML-2) proteaseEndogenous retrovirus group K member 10 Pol protein proteaseRetroviral aspartyl proteaseHML-2 protease

Inhibition of the aspartic protease activity to prevent the cleavage of Gag and Gag-Pol polyproteins, thereby blocking viral maturation and protein-mediated toxicity (PubMed: 17604210).