Inhibitors of HIV-1 Nef: applications and developments for a practical cure Volume 26, issue 1, Janvier-Février 2022


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1 Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, Room 3007J, 1151 Richmond St, N6A5C1 London, Ontario, Canada
2 Biotherapeutics Research Laboratory, Robarts Research Institute, London, Ontario, Canada
* Correspondance

Antiretroviral therapy can control human immunodeficiency virus type 1 (HIV-1) replication in people living with HIV; however, these treatments are not curative and no practical approach for an HIV-1 cure has yet shown success in clinical trials. Counteracting the multiple barriers HIV-1 presents against a practical cure is a direct means to functionalize these curative approaches in vivo. Pharmacological inhibition of the HIV-1 accessory protein, Nef, represents a particularly promising and ambitious approach, with Nef inhibitors holding the potential to reverse HIV-1-related defects in T cell receptor and kinase signaling, apoptosis, autophagy and most importantly, antigen presentation. Together, the capacity for Nef inhibitors to restore these activities underscores their potential as supportive agents in a practical HIV-1 cure. In this review, we outline a rationale for pharmacologically targeting Nef and review the progress made in the identification and development of Nef inhibitors.