RD6-2198, a novel betain-type fluoroalkylated oligomer, inhibits the replications of human immunodeficiency virus type 1 and other enveloped viruses.
We have examined a novel betain-type fluoroalkylated oligomer, RD6-2198, for its inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses, including herpes simplex virus types 1 and 2 (HSV-1 and HSV-2, respectively) and respiratory syncytial virus (RSV) in cell cultures. We have found that the compound is a potent and selective inhibitor of these viruses. RD6-2198 inhibited the replication of HIV-1IIIB at a concentration of 0.85 microg/ml with a selectivity index greater than 59 in MT-4 cells. Furthermore, its 50% effective concentration (EC50) values for HSV-1, HSV-2 and RSV, were 0.51, 0.94 and 3.0 microg/ml, respectively. We found that the RD6-2198 suppressed the gp120-CD4 interaction (as monitored by an enzyme-linked immunosorbent assay (ELISA) method). RD6-2198 also inhibited the binding of anti-gp120 monoclonal antibody to gp120 expressed on MOLT-4/IIIB cells (MOLT-4 cells chronically infected with HIV-1IIIB). However, the compound did not inhibit the interaction of anti-CD4 antibody with CD4. These results suggest that RD6-2198 interacts with the viral envelope glycoprotein and thereby inhibits the viral adsorption process. In addition, RD6-2198 was also found to suppress the proliferation of MOLT-4/IIIB cells. When applied topically, RD6-2198 at a concentration of 10 mg/ml completely protected mice from an intravaginal HSV-2 infection.
Rational Drug Design Laboratories, Matsukawamachi, Fukushima, Japan. fuji@rdl.co.jp
M
M
Fujiwara
N
N
Ashida
M
M
Okamoto
T
T
Mizuta
T
T
Ide
Y
Y
Hanasaki
K
K
Katsuura
H
H
Sawada
S
S
Shigeta
K
K
Konno
T
T
Yokota
M
M
Baba
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000633:toxicity; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology*; D001622:Betaine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D015704:CD4 Antigens / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016264:Dextran Sulfate / Q000494:pharmacology; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006558:Herpes Genitalis / Q000188:drug therapy / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D012136:Respiratory Syncytial Viruses / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; C114790:RD6 2198; D001622:Betaine; D016264:Dextran Sulfate