University:
University of North Carolina at Chapel Hill
Course:
NURS 312 | Pharmacology
Academic year:

2020
Views:

271

Pages:

1
Author:

Alexa Livingston

6.4 – “How HIV wa wass thwarted at the Gates of Camelot”: Entry inhibitors, fu fusion sion inhibitors, inte integrase grase inhibitors • HIV infects macrophage, dendritic cells, & CD4 T-cells (crusader cross on neighboring castle). Once incorporated into host DNA, commandeers host machinery to transcribe viral genes. Gag, pol, env code for polyprotein precursors that produce viral virions, which will then bud off and invade next cells o gag structural gene encodes for virion core proteins, including p7 & p24 (sundial, gagged prisoners guarded 24/7) o env structural gene encodes envelope proteins including gp41 & gp120 needed for infiltrating membrane of host cells (envoy boat). Proteins are initially sent to the host cell ER for processing (reef around env boat) o pol gene encodes for proteases, reverse transcriptase, and integrase (Paul the blacksmith) • HIV invasion 1) For HIV to infect a cell, HIV surface glycoprotein gp120 must bind host cell CD4 molecule + a chemokine R (CCR5 or CXCR4) (envoy gaining entry with 120 battering ram; helper squire and CCR5 banners). 2) Fusion. Gp41 facilitates HIV fusion (envoy throwing 41 grappling hooks over castle walls). 3) Once inside the cell, RT transcribes viral RNA into dsDNA (reverso transcriptum spell book) 4) Integrase allows viral DNA to integrate into host cell DNA (keys to unlock nucleus of castle with double helix stairs) • Entry inhibitors o Maraviroc (rearing mare) binds CCR5 receptor, blocking HIV binding and consequent invasion. Before beginning therapy, should determine if HIV strain invades via CCR5. • Fusion inhibitors o Enfuvirtide binds gp41 surface protein, preventing fusion (knight on wall deflecting grappling hook; enfuvirtide for fusion) • NRTIs & NNRTIs act against RT (King Arthur & Queen Elfavir defending the castle) o Mutations to pol gene confer resistance to these classes as well as protease inhibitors & integrase inhibitors (Paul the blacksmith making swords, spell books, and keys for proteases, RT, & integrases respectively). • Integrase inhibitors o Raltegravir disrupts ability of HIV DNA to integrate into host chromosomes; may also be considered to prevent transcription of viral mRNA (knight deflecting key) o Mutations to pol gene confer resistance (mutated key not deflected by slacking knight) o May rarely cause rhabdomyolysis (bite out of chicken leg)