Nursing Pharmacology: Antiviral Drugs

**Sites of Antiretroviral Drug Actions¹⁰**

a: The lifecycle of HIV-1, showing the step at which enfuvirtide acts, and also the steps targeted by other drugs.¹⁶0 b: "Simplified schematic of the mechanism by which enfuvirtide inhibits viral entry into host cells.¹⁰ The envelope glycoprotein of HIV-1 consists of two non-covalently associated subunits, gp120 and gp41. After attachment of HIV-1 to its target cells carrying the CD4 receptor, gp120 interacts with the CD4 receptor, which initiates a series of conformational changes in gp41 and gp120 that lead to the insertion of a region of gp41 into the membrane of the host cell, and formation of a ' pre-hairpin intermediate' (top). Further changes in the confirmation of gp41 bring the viral and cellular membranes into close enough proximity for membrane fusion (bottom left). Abbreviations: NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor" Attribution: Slight modification of Figure 1 from: LaBonte J Lebbos J Kirkpatrick nature Reviews Drug Discovery 2, 345-346 (May 2003).¹⁰

**"The Discovery and Development of Inhibitors of HIV-1 Integrase"¹²**

Huzuda D and the Merck Integrase Inhibitor Team The Discover and Development of Inhibitors of HIV-1 Integrase https://www.youtube.com/watch?v=HZBEq8ZBR4g, (12/2009) UC Berkeley Events YouTube Channel: https://www.youtube.com/channel/UCFkid-1EIBbauJLbMFDp2Cg

References
Flexner C Antiretroviral Agents and Treatment of HIV Infection, Chapter 59 in Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12th edition (Brunton LL Chabner BA Knollmann BC, eds; Brunton LL, ed; Blumenthal DK Murri N Hilal-Dandan R, assoc eds, Knollmann BC, consulting ed, on-line edition) The McGraw-Hill Companies, 2011. Fauci AS Lane HC Chapter 226, Human Immunodeficiency Virus Disease: AIDS and Related Disorders, in Harrison's Online (Kasper DL Fauci AS Hauser SL Longo DL Jameson JL Loscalzo J, Eds.), Harrison's Principles of Internal Medicine, 19th edition, The McGraw-Hill Companies, Inc. 2015 (on-line edition) Longo DL Fauci AS 188, The Human Retroviruses, in Harrison's Online (Dan L. Longo, Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, J. Larry Jameson, Joseph Loscalzo, Eds.), Harrison's Principles of Internal Medicine, 18th edition, The McGraw-Hill Companies, Inc. 2012. Woster PM Chapter 43: Antiviral Agents and Protease Inhibitors in Foye's Principles of Medicinal Chemistry 6e, Lemke, TL Williams DA, eds; Roche VG Zito SW, asst eds) Wolters Kluwer\|Lippincott Williams & Wilkins 1214, 2008. HIV Overview: The HIV Life Cycle, Education Materials, AIDSinfo, NIH http://aidsinfo.nih.gov/education-materials/fact-sheets/19/73/the-hiv-life-cycle Tsibris AMN Hirsch MS Chapter 130 Antiretroviral Therapy for Human Immunodeficiency Virus Infection in Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8e (Bennett JE Bolin R Blaser, eds) Elsevier, Inc/Saunders 2015, online version. Safrin S Chapter 49: Antiviral Agents: Antiretroviral Agents in Basic & Clinical Pharmacology 13e (Katzung BG Trevor AJ, eds) 2015, online edition. Wensing AM Calvez V Gunthard JF Johnson VA Paredes R Pillay D Shafer RW Richman DD Special Contribution: 2014 Update of the Drug Resistance Multations in HIV-1 Topics in Antivral Medicine 22(3) June/July 2014, https://www.iasusa.org/sites/default/files/tam/22-3-642.pdf AIDSinfo: Guidelines for the Use of Antriretroviral Agents in HIV-1-Infected Adults and Adolescents https://aidsinfo.nih.gov/guidelines (2015) LaBonte J Lebbos J Kirkpatrick nature Reviews Drug Discovery 2, 345-346 (May 2003). (Slight modification of Fig. 1) http://www.nature.com/nrd/journal/v2/n5/fig_tab/nrd1091_F1.html; Original figure attribution: Kilby JM Hopkins S Venetta TM Hicks C Gulick RM Raltegravir: The First HIV Type 1 Integrase Inhibitor. Clin Infect Disease Apr. 1; 48(7): 931-939 2009. http://www-ncbi-nlm-nih-gov.proxy.kumc.edu:2048/pubmed/19231980. Huzuda D and the Merck Integrase Inhibitor Team (Inhibitors of HIV-1 Integrase: From the Bench to the Bedside, and Back Again) https://www.youtube.com/watch?v=HZBEq8ZBR4g, 21 February, 2009; uploaded Dec. 22, 2009. PommierY Hohnson AA Marchand C Integrase Inhibitors to Treat HIV/AIDS Nature Review (Drug Discovery) 4: 235-248 March 2005 (http://discover.nci.nih.gov/pommier/2005.Pommier.nrd.pdf) Hopur: "Structure active relationship of elvitegravir and raltegravir. Benzyl group in a hydrophobic pocket and a triad to chelate the two Mg²⁺ ions." https://commons.wikimedia.org/wiki/File:SAR_of_elvitegravir_and_raltegravir.png

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