Entry of hepatitis C virus and human immunodeficiency virus is selectively inhibited by carbohydrate-binding agents but not by polyanions.
We studied the antiviral activity of carbohydrate-binding agents (CBAs), including several plant lectins and the non-peptidic small-molecular-weight antibiotic pradimicin A (PRM-A). These agents efficiently prevented hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infection of target cells by inhibiting the viral entry. CBAs were also shown to prevent HIV and HCV capture by DC-SIGN-expressing cells. Surprisingly, infection by other enveloped viruses such as herpes simplex viruses, respiratory syncytial virus and parainfluenza-3 virus was not inhibited by these agents pointing to a high degree of specificity. Mannan reversed the antiviral activity of CBAs, confirming their association with viral envelope-associated glycans. In contrast, polyanions such as dextran sulfate-5000 and sulfated polyvinylalcohol inhibited HIV entry but were devoid of any activity against HCV infection, indicating that they act through a different mechanism. CBAs could be considered as prime drug leads for the treatment of chronic viral infections such as HCV by preventing viral entry into target cells. They may represent an attractive new option for therapy of HCV/HIV coinfections. CBAs may also have the potential to prevent HCV/HIV transmission.
Bertaux
Claire
C
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
Daelemans
Dirk
D
Meertens
Laurent
L
Cormier
Emmanuel G
EG
Reinus
John F
JF
Peumans
Willy J
WJ
Van Damme
Els J M
EJ
Igarashi
Yasuhiro
Y
Oki
Toshikazu
T
Schols
Dominique
D
Dragic
Tatjana
T
Balzarini
Jan
J
D000818:Animals; D000838:Anions / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D050260:Carbohydrate Metabolism; D045744:Cell Line, Tumor; D006678:HIV / Q000187:drug effects / Q000502:physiology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects / Q000502:physiology; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D014779:Virus Replication
D000838:Anions; D000998:Antiviral Agents