Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus (HIV).
Glycyrrhizin (GL) achieved a dose-dependent inhibition of the replication of human immunodeficiency virus type 1 (HIV-1) in MOLT-4 (clone No. 8) cells within the concentration range of 0.075 to 0.6 mM. Within this concentration range, GL also effected a dose-dependent reduction in the protein kinase C (PKC) activity of MOLT-4 (clone No. 8) cells. A well-known PKC inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), also proved inhibitory to HIV-1 replication in MOLT-4 (clone No. 8) cells. PKC inhibition may thus be considered as one of the mechanisms by which GL inhibits HIV-1 replication. In addition, GL may also owe its anti-HIV-1 activity, at least in part, to an interference with virus-cell binding, since the compound at 1.2 mM partially inhibited the adsorption of radiolabeled HIV-1 particles to MT-4 cells. At this concentration GL also suppressed giant cell formation induced by co-culturing MOLT-4 (clone No. 8) cells with MOLT-4/HTLV-IIIB cells, whereas the PKC inhibitor H-7 failed to do so.
Ito
M
M
Department of Bacteriology, Fukushima Medical College, Japan.
Sato
A
A
Hirabayashi
K
K
Tanabe
F
F
Shigeta
S
S
Baba
M
M
De Clercq
E
E
Nakashima
H
H
Yamamoto
N
N
D000327:Adsorption; D000998:Antiviral Agents / Q000494:pharmacology*; D002999:Clone Cells; D003588:Cytopathogenic Effect, Viral; D004305:Dose-Response Relationship, Drug; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D015488:HIV Antigens / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015488:HIV Antigens; D019695:Glycyrrhizic Acid; D011493:Protein Kinase C; D006034:Glycyrrhetinic Acid