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Exploring Drug Resistance in HIV‐1 Protease using 3D Printed Models
Author(s) -
Villeda Adan,
Chivington Austin,
Cobos Maximilian,
Gastineau Thomas,
Mares Cesar,
Que Javier,
Porter Lon A.,
Novak Walter R.P.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06361
Subject(s) - darunavir , protease , hiv 1 protease , drug resistance , virology , reverse transcriptase , human immunodeficiency virus (hiv) , rnase h , hiv drug resistance , biology , protease inhibitor (pharmacology) , drug , genetics , enzyme , pharmacology , antiretroviral therapy , viral load , biochemistry , rna , gene
HIV roughly affects 38 million people around the world. The enzyme HIV‐1 protease is essential for replication and maturation of the virus. HIV‐1 protease activates a variety of important proteins including reverse transcriptase and RNase H. Darunavir, an HIV‐1 protease inhibitor, is the most potent antiretroviral drug to combat HIV to date. Despite the potency of Darunavir, HIV‐1 protease can develop mutations both inside and outside of its active site to render Darunavir and other inhibitors ineffective. Here we develop 3D printed models to illustrate the structural basis of drug resistance. Specifically, we model the mutations V32I and L76V in HIV‐1 protease. Hands‐on models that illustrate resistance mutations near the active site of HIV‐1 protease provide students with additional visual references to better understand drug resistance mechanisms and the design of novel inhibitors to effectively overcome these mutations. Support or Funding Information This work was funded in part by NSF‐IUSE 1725940 for the CREST Project.