Antiviral activity of chondroitin sulphate E targeting dengue virus envelope protein.
Sulphated glycosaminoglycans such as heparin inhibit the early step of dengue virus infection through interaction with envelope (E) protein. Here, we found that chondroitin sulphate E (CSE), but not CSD, which contains the same degree of sulphation, inhibited dengue virus (DENV) infection of cells with adsorption. CSE significantly reduced infectivity of all dengue virus serotypes to BHK-21 and Vero cells. DENV preferentially bound to CSE immobilised on plastic plates. Also, virus binding to CSE or heparin was cross-inhibited by soluble CSE or heparin. These findings suggested that common carbohydrate determinants on CSE and heparin could be essential epitopes for interaction of DENV, and may be responsible for inhibition of the early steps of DENV infection. A recombinant E protein directly bound heparin and CSE, but not CSD, meaning that interaction of CSE with E protein contributes to the inhibitory action of this glycosaminoglycan. These observations indicate that a specific carbohydrate structure rather than polysulphation or addition of negative charges of the glycosaminoglycan molecule would be necessary for direct binding to DENV E protein. In conclusion, CSE showed antiviral activity as an entry inhibitor targeting E protein of dengue virus.
Kato
Daisuke
D
Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, and Global COE Program for Innovation in Human Health Sciences, 52-1 Yada, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan.
Era
Shota
S
Watanabe
Ippei
I
Arihara
Masataka
M
Sugiura
Nobuo
N
Kimata
Koji
K
Suzuki
Yasuo
Y
Morita
Kouichi
K
Hidari
Kazuya I P J
KI
Suzuki
Takashi
T
D000330:Aedes; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D002522:Chlorocebus aethiops; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D003716:Dengue Virus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D006025:Glycosaminoglycans / Q000494:pharmacology; D006497:Heparan Sulfate / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000494:pharmacology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors*; D053585:Virus Attachment / Q000187:drug effects*; D053586:Virus Internalization
D000998:Antiviral Agents; D002809:Chondroitin Sulfates; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D014759:Viral Envelope Proteins