MOLECULAR TARGETS FOR AIDS THERAPY

被引:777
作者
MITSUYA, H
YARCHOAN, R
BRODER, S
机构
[1] National Cancer Institute, National Institutes of Health, Bethesda
关键词
D O I
10.1126/science.1699273
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The development of antiretroviral therapy against acquired immunodeficiency syndrome (AIDS) has been an intense research effort since the discovery of the causative agent, human immunodeficiency virus (HIV). A large array of drugs and biologic substances can inhibit HIV replication in vitro. Nucleoside analogs - particularly those belonging to the dideoxynucleoside family - can inhibit reverse transcriptase after anabolic phosphorylation. 3′-Azido-2′, 3′-dideoxythymidine (AZT) was the first such drug tested in individuals with AIDS, and considerable knowledge of structure-activity relations has emerged for this class of drugs. However, virtually every step in the replication of HIV could serve as a target for a new therapeutic intervention. In the future, non-nucleoside-type drugs will likely become more important in the experimental therapy of AIDS, and antiretroviral therapy will exert major effects against the morbidity and mortality caused by HIV.
引用
收藏
页码:1533 / 1544
页数:12
相关论文
共 245 条
[1]   ORAL DEXTRAN SULFATE (UA001) IN THE TREATMENT OF THE ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) AND AIDS-RELATED COMPLEX [J].
ABRAMS, DI ;
KUNO, S ;
WONG, R ;
JEFFORDS, K ;
NASH, M ;
MOLAGHAN, JB ;
GORTER, R ;
UENO, R .
ANNALS OF INTERNAL MEDICINE, 1989, 110 (03) :183-188
[2]   INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS IN EARLY INFECTED AND CHRONICALLY INFECTED-CELLS BY ANTISENSE OLIGODEOXYNUCLEOTIDES AND THEIR PHOSPHOROTHIOATE ANALOGS [J].
AGRAWAL, S ;
IKEUCHI, T ;
SUN, D ;
SARIN, PS ;
KONOPKA, A ;
MAIZEL, J ;
ZAMECNIK, PC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (20) :7790-7794
[3]   INITIAL STUDIES ON THE CELLULAR PHARMACOLOGY OF 2',3'-DIDEOXYINOSINE, AN INHIBITOR OF HIV INFECTIVITY [J].
AHLUWALIA, G ;
COONEY, DA ;
MITSUYA, H ;
FRIDLAND, A ;
FLORA, KP ;
HAO, Z ;
DALAL, M ;
BRODER, S ;
JOHNS, DG .
BIOCHEMICAL PHARMACOLOGY, 1987, 36 (22) :3797-3800
[4]  
AHLUWALIA G, 1988, J BIOL CHEM, V29, P349
[5]  
AHLUWALIA GS, UNPUB
[6]   MUTATIONS OF RNA AND PROTEIN SEQUENCES INVOLVED IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PACKAGING RESULT IN PRODUCTION OF NONINFECTIOUS VIRUS [J].
ALDOVINI, A ;
YOUNG, RA .
JOURNAL OF VIROLOGY, 1990, 64 (05) :1920-1926
[7]   RIBAVIRIN ANTAGONIZES INHIBITORY EFFECTS OF PYRIMIDINE 2',3'-DIDEOXYNUCLEOSIDES BUT ENHANCES INHIBITORY EFFECTS OF PURINE 2',3'-DIDEOXYNUCLEOSIDES ON REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS INVITRO [J].
BABA, M ;
PAUWELS, R ;
BALZARINI, J ;
HERDEWIJN, P ;
DECLERCQ, E ;
DESMYTER, J .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1987, 31 (10) :1613-1617
[8]   PENTOSAN POLYSULFATE, A SULFATED OLIGOSACCHARIDE, IS A POTENT AND SELECTIVE ANTI-HIV AGENT INVITRO [J].
BABA, M ;
NAKAJIMA, M ;
SCHOLS, D ;
PAUWELS, R ;
BALZARINI, J ;
DECLERCQ, E .
ANTIVIRAL RESEARCH, 1988, 9 (06) :335-343
[9]   MECHANISM OF INHIBITORY EFFECT OF DEXTRAN SULFATE AND HEPARIN ON REPLICATION OF HUMAN IMMUNODEFICIENCY VIRUS INVITRO [J].
BABA, M ;
PAUWELS, R ;
BALZARINI, J ;
ARNOUT, J ;
DESMYTER, J ;
DECLERCQ, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (16) :6132-6136
[10]   SELECTIVE-INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) BY 3'-AZIDO-2',3'-DIDEOXYGUANOSINE INVITRO [J].
BABA, M ;
PAUWELS, R ;
BALZARINI, J ;
HERDEWIJN, P ;
DECLERCQ, E .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1987, 145 (03) :1080-1086