Potent and selective inhibition of human immunodeficiency virus (HIV)-1 and HIV-2 replication by a class of bicyclams interacting with a viral uncoating event.
- 15 June 1992
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 89 (12) , 5286-5290
- https://doi.org/10.1073/pnas.89.12.5286
Abstract
A series of bicyclams have been shown to be potent and selective inhibitors of human immunodeficiency virus (HIV). The compounds are inhibitory to the replication of various HIV-1 and HIV-2 strains in various human T-cell systems, including peripheral blood lymphocytes, at 0.14-1.4 microM, without being toxic to the host cells at 2.2 mM. The bicyclam JM2763 is active against 3'-azido-3'-deoxythymidine (zidovudine; AZT)-resistant HIV-1 strains and acts additively with AZT. Mechanism of action studies revealed that the bicyclams (i.e., JM2763) interact with an early event of the retrovirus replicative cycle, which could be tentatively identified as a viral uncoating event.Keywords
This publication has 43 references indexed in Scilit:
- Design, Activity, and 2.8 Å Crystal Structure of a C 2 Symmetric Inhibitor Complexed to HIV-1 ProteaseScience, 1990
- Rational Design of Peptide-Based HIV Proteinase InhibitorsScience, 1990
- Inhibition of HIV-1 protease in infected T-lymphocytes by synthetic peptide analoguesNature, 1990
- Highly specific inhibition of human immunodeficiency virus type 1 by a novel 6-substituted acyclouridine derivativeBiochemical and Biophysical Research Communications, 1989
- Clinical Pharmacology of 3'-Azido-2',3'-Dideoxythymidine (Zidovudine) and Related DideoxynucleosidesNew England Journal of Medicine, 1989
- Syncytium Formation and Destruction of Bystander CD4+ Cells Cocultured with T Cells Persistently Infected with Human Immunodeficiency Virus as Demonstrated by Flow CytometryJournal of General Virology, 1989
- The structure of antiviral agents that inhibit uncoating when complexed with viral capsidesAntiviral Research, 1989
- The 2′,3′-dideoxyriboside of 2,6-diaminopurine and its 2′,3′-didehydro derivative inhibit the deamination of 2′,3′-dideoxyadenosine, an inhibitor of human immunodeficiency virus (HIV) replicationBiochemical and Biophysical Research Communications, 1987
- Infection of HTLV-III/LAV in HTLV-I-Carrying Cells MT-2 and MT-4 and Application in a Plaque AssayScience, 1985
- Detection, Isolation, and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDSScience, 1984