Protease Inhibitors

Protease inhibitors are a group of medications used to treat HIV and other viral infections. Protease inhibitors work by inhibiting the HIV aspartyl protease enzyme, which is responsible for cleaving the viral polypeptide into critical enzymes and structural proteins. Ritonavir is generally administered with other medications to enhance their effect. Ritonavir works in combination with nirmatrelvir for the treatment of COVID-19.   Protease inhibitors generally inhibit the CYP450 system so many drug-drug interactions occur.

Class Drugs

• Atazanavir

• Darunavir

• Fosamprenavir

• Indinavir

• Lopinavir

• Nirmatrelvir

• Nelfinavir

• Ritonavir

• Saquinavir

• Tipranavir

Class Mechanism of Action

Inhibits HIV aspartyl protease

• HIV aspartyl protease cleaves the viral polypeptide into critical enzymes and structural proteins

Class Applications

HIV

See individual drugs for further applications

Class Adverse Effects

Central and base of neck adiposity develops and loss of fat from extremities occurs

Drug-drug interactions: Inhibits CYP450 system

Resistance

• Mutations of protease gene

Drug Table

Drug Name	Application	Comments	Image
Atazanavir		Adverse Reactions; Hyperbilirubinemia, benign; Jaundice, benign	"Tasmanian Devil" "Anna"
Darunavir		Co-administered with ritonavir	"DARE" "Uma Thurman"
Fosamprenavir		Co-administered with ritonavir	"Frost" "Amp" "Rent"
Indinavir		Adverse Effects; Nephrolithiasis (kidney stones); Hyperbilirubinemia	"India" "Navigation"
Lopinavir		Co-administered with ritonavir	"Lop" "Navigation"
Nelfinavir		Co-administered with ritonavir	"Nerf" "Navigation"
Nirmatrelvir	COVID-19		"Nerve" "Mater (CARS Movie)"
Ritonavir	Used to "boost" other protease inhibitors as it strongly inhibits CYP3A system and allows the combined protease inhibitor to be more available to assert its actionCOVID-19	Adverse Reactions; Bone marrow toxicity; Neutropenia; Anemia	"Rattan" "Navigation"
Saquinavir		Co-administered with ritonavir	"Sack" "Dr. Quinn Medicine Woman"
Tipranavir		Co-administered with ritonavir; Adverse Effects; Potentially fatal hepatitis; Intracranial hemorrhage, rare	"Tip" "Ran"