Abstract
A marine-derived compound, abalone hemocyanin, from Haliotis rubra was shown to have a unique mechanism of antiviral activity against herpes simplex virus 1 (HSV-1) infections. In vitro assays demonstrated the dose-dependent and inhibitory effect of purified hemocyanin against HSV-1 infection in Vero cells with a 50% effective dose (ED50) of 40 to 50 nM and no significant toxicity. In addition, hemocyanin specifically inhibited viral attachment and entry by binding selectively to the viral surface glycoproteins gD, gB, and gC, probably by mimicking their receptors. However, hemocyanin had no effect on postentry events and did not block infection by binding to cellular receptors for HSV. By the use of different mutants of gD and gB and a competitive heparin binding assay, both protein charge and conformation were shown to be the driving forces of the interaction between hemocyanin and viral glycoproteins. These findings also suggested that hemocyanin may have different motifs for binding to each of the viral glycoproteins B and D. The dimer subunit of hemocyanin with a 10-fold-smaller molecular mass exhibited similar binding to viral surface glycoproteins, showing that the observed inhibition did not require the entire multimer. Therefore, a small hemocyanin analogue could serve as a new antiviral candidate for HSV infections.
| Original language | English |
|---|---|
| Pages (from-to) | 1003-1012 |
| Number of pages | 10 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 60 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1 Feb 2016 |
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ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology
- Infectious Diseases
Cite this
Abalone hemocyanin blocks the entry of herpes simplex virus 1 into cells : A potential new antiviral strategy. / Talaei Zanjani, Negar; Miranda-Saksena, Monica; Valtchev, Peter; Diefenbach, Russell J.; Hueston, Linda; Diefenbach, Eve; Mohd Sairi, Mohd Fareed; Gomes, Vincent G.; Cunningham, Anthony L.; Dehghani, Fariba.
In: Antimicrobial Agents and Chemotherapy, Vol. 60, No. 2, 01.02.2016, p. 1003-1012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Abalone hemocyanin blocks the entry of herpes simplex virus 1 into cells
T2 - A potential new antiviral strategy
AU - Talaei Zanjani, Negar
AU - Miranda-Saksena, Monica
AU - Valtchev, Peter
AU - Diefenbach, Russell J.
AU - Hueston, Linda
AU - Diefenbach, Eve
AU - Mohd Sairi, Mohd Fareed
AU - Gomes, Vincent G.
AU - Cunningham, Anthony L.
AU - Dehghani, Fariba
PY - 2016/2/1
Y1 - 2016/2/1
N2 - A marine-derived compound, abalone hemocyanin, from Haliotis rubra was shown to have a unique mechanism of antiviral activity against herpes simplex virus 1 (HSV-1) infections. In vitro assays demonstrated the dose-dependent and inhibitory effect of purified hemocyanin against HSV-1 infection in Vero cells with a 50% effective dose (ED50) of 40 to 50 nM and no significant toxicity. In addition, hemocyanin specifically inhibited viral attachment and entry by binding selectively to the viral surface glycoproteins gD, gB, and gC, probably by mimicking their receptors. However, hemocyanin had no effect on postentry events and did not block infection by binding to cellular receptors for HSV. By the use of different mutants of gD and gB and a competitive heparin binding assay, both protein charge and conformation were shown to be the driving forces of the interaction between hemocyanin and viral glycoproteins. These findings also suggested that hemocyanin may have different motifs for binding to each of the viral glycoproteins B and D. The dimer subunit of hemocyanin with a 10-fold-smaller molecular mass exhibited similar binding to viral surface glycoproteins, showing that the observed inhibition did not require the entire multimer. Therefore, a small hemocyanin analogue could serve as a new antiviral candidate for HSV infections.
AB - A marine-derived compound, abalone hemocyanin, from Haliotis rubra was shown to have a unique mechanism of antiviral activity against herpes simplex virus 1 (HSV-1) infections. In vitro assays demonstrated the dose-dependent and inhibitory effect of purified hemocyanin against HSV-1 infection in Vero cells with a 50% effective dose (ED50) of 40 to 50 nM and no significant toxicity. In addition, hemocyanin specifically inhibited viral attachment and entry by binding selectively to the viral surface glycoproteins gD, gB, and gC, probably by mimicking their receptors. However, hemocyanin had no effect on postentry events and did not block infection by binding to cellular receptors for HSV. By the use of different mutants of gD and gB and a competitive heparin binding assay, both protein charge and conformation were shown to be the driving forces of the interaction between hemocyanin and viral glycoproteins. These findings also suggested that hemocyanin may have different motifs for binding to each of the viral glycoproteins B and D. The dimer subunit of hemocyanin with a 10-fold-smaller molecular mass exhibited similar binding to viral surface glycoproteins, showing that the observed inhibition did not require the entire multimer. Therefore, a small hemocyanin analogue could serve as a new antiviral candidate for HSV infections.
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UR - http://www.scopus.com/inward/citedby.url?scp=84957922920&partnerID=8YFLogxK
U2 - 10.1128/AAC.01738-15
DO - 10.1128/AAC.01738-15
M3 - Article
VL - 60
SP - 1003
EP - 1012
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 2
ER -