The Drug-Induced Interface That Drives HIV-1 Integrase Hypermultimerization and Loss of Function

Author:

Singer Matthew R.1,Dinh Tung2,Levintov Lev3,Annamalai Arun S.2,Rey Juan S.3,Briganti Lorenzo2,Cook Nicola J.1,Pye Valerie E.1,Taylor Ian A.4,Kim Kyungjin5,Engelman Alan N.67,Kim Baek89,Perilla Juan R.3ORCID,Kvaratskhelia Mamuka2ORCID,Cherepanov Peter110ORCID

Affiliation:

1. Chromatin Structure & Mobile DNA Laboratory, The Francis Crick Institute, London, United Kingdom

2. Division of Infectious Diseases, School of Medicine, University of Colorado, Aurora, Colorado, USA

3. Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware, USA

4. Macromolecular Structure Laboratory, The Francis Crick Institute, London, United Kingdom

5. ST Pharm Co. Ltd., Seoul, South Korea

6. Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

7. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA

8. Center for Drug Discovery, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA

9. Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, USA

10. Department of Infectious Disease, St-Mary's Campus, Imperial College London, London, United Kingdom

Abstract

Despite the remarkable success of combination antiretroviral therapy, HIV-1 remains among the major causes of human suffering and loss of life in poor and developing nations. To prevail in this drawn-out battle with the pandemic, it is essential to continue developing advanced antiviral agents to fight drug resistant HIV-1 variants.

Funder

Medical Research Council

Cancer Research UK

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of General Medical Sciences

Wellcome Trust

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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