Lopinavir is a Selective Peptidomimetic Inhibitor of the HIV-1 Protease

HIV protease, a homodimeric aspartyl protease, is an essential component of the Human Immunodeficiency Virus genome. HIV protease is responsible for cleaving the Gag and Gag-Pol polyproteins in a late stage of the viral life cycle. Hence it can create mature protein components of an infectious virus, such as structural (matrix, capsid, nucleocapsid) and enzymatic (protease, reverse transcriptase, integrase) proteins. These allow assembly of the viral virions and remodeling to product infectious viral particles, as well as providing for the next round of replication upon infection of new cells. Therefore, without effective HIV protease, HIV virions remain uninfectious.

HIV-1 protease permits viral maturation by processing the Gag and Gag-Pro-Pol polyproteins. HIV-1 protease exhibits broad substrate recognition. It recognizes and cleaves more than 12 different substrates leading to viral maturation. HIV-1 protease is involved with peptide bond hydrolysis in retroviruses. And this is essential for the life-cycle of HIV, the retrovirus that causes AIDS. Because there is no corresponding aspartyl protease that cleaves the Gag polyprotein in mammalian cells, HIV protease has been a popular target for antiretroviral drug development.

Lopinavir is a potent and selective HIV-1 protease inhibitor

Lopinavir is a highly potent, selective peptidomimetic inhibitor of the HIV-1 protease. Importantly, Lopinavir can inhibit wild-type and mutant HIV protease at pM concentrations. Lopinavir acts by arresting maturation of HIV-1 thereby blocking its infectivity. What’s more, Lopinavir is also an inhibitor of the severe acute respiratory syndrome coronavirus (SARS-CoV) main protease, which is critical for replication. Lopinavir has in vitro inhibitory activity against SARS-CoV, SARS-CoV-2, and Middle East respiratory syndrome (MERS) coronavirus. Coadministration with low-dose Ritonavir significantly increases plasma half-life of Lopinavir.

All in all, Lopinavir is a potent and selective peptidomimetic inhibitor of the HIV-1 protease. Lopinavir also can inhibit the severe acute respiratory syndrome coronavirus (SARS-CoV) main protease.

[1]. Brik A, et, al. Org Biomol Chem. 2003 Jan 7;1(1):5-14.