Virucidal activity of the dendrimer microbicide SPL7013 against HIV-1

Sushama Telwatte, Katie Moore, Adam Johnson, David Tyssen, Jasminka Sterjovski, Muriel Aldunate, Paul R Gorry, Paul Ramsland, Gareth Lewis, Jeremy Paull, Secondo Sonza, Gilda Tachedjian

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Abstract

Topical microbicides for use by women to prevent the transmission of human immunodeficiency virus (HIV) and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. SPL7013 is a dendrimer with broad-spectrum activity against HIV type I (HIV-1) and -2 (HIV-2), herpes simplex viruses type-1 (HSV-1) and -2 (HSV-2) and human papillomavirus. SPL7013 [3 (w/w)] has been formulated in a mucoadhesive carbopol gel (VivaGel(R)) for use as a topical microbicide. Previous studies showed that SPL7013 has similar potency against CXCR4-(X4) and CCR5-using (R5) strains of HIV-1 and that it blocks viral entry. However, the ability of SPL7013 to directly inactivate HIV-1 is unknown. We examined whether SPL7013 demonstrates virucidal activity against X4 (NL4.3, MBC200, CMU02 clade EA and 92UG046 clade D), R5 (Ba-L, NB25 and 92RW016 clade A) and dual-tropic (R5X4; MACS1-spln) HIV-1 using a modified HLA-DR viral capture method and by polyethylene glycol precipitation. Evaluation of virion integrity was determined by ultracentrifugation through a sucrose cushion and detection of viral proteins by Western blot analysis. SPL7013 demonstrated potent virucidal activity against X4 and R5X4 strains, although virucidal activity was less potent for the 92UG046 X4 clade D isolate. Where potent virucidal activity was observed, the 50 virucidal concentrations were similar to the 50 effective concentrations previously reported in drug susceptibility assays, indicating that the main mode of action of SPL7013 is by direct viral inactivation for these strains....
Original languageEnglish
Pages (from-to)195 - 199
Number of pages5
JournalAntiviral Research
Volume90
Issue number3
DOIs
Publication statusPublished - 2011

Cite this

Telwatte, S., Moore, K., Johnson, A., Tyssen, D., Sterjovski, J., Aldunate, M., ... Tachedjian, G. (2011). Virucidal activity of the dendrimer microbicide SPL7013 against HIV-1. Antiviral Research, 90(3), 195 - 199. https://doi.org/10.1016/j.antiviral.2011.03.186
Telwatte, Sushama ; Moore, Katie ; Johnson, Adam ; Tyssen, David ; Sterjovski, Jasminka ; Aldunate, Muriel ; Gorry, Paul R ; Ramsland, Paul ; Lewis, Gareth ; Paull, Jeremy ; Sonza, Secondo ; Tachedjian, Gilda. / Virucidal activity of the dendrimer microbicide SPL7013 against HIV-1. In: Antiviral Research. 2011 ; Vol. 90, No. 3. pp. 195 - 199.
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abstract = "Topical microbicides for use by women to prevent the transmission of human immunodeficiency virus (HIV) and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. SPL7013 is a dendrimer with broad-spectrum activity against HIV type I (HIV-1) and -2 (HIV-2), herpes simplex viruses type-1 (HSV-1) and -2 (HSV-2) and human papillomavirus. SPL7013 [3 (w/w)] has been formulated in a mucoadhesive carbopol gel (VivaGel(R)) for use as a topical microbicide. Previous studies showed that SPL7013 has similar potency against CXCR4-(X4) and CCR5-using (R5) strains of HIV-1 and that it blocks viral entry. However, the ability of SPL7013 to directly inactivate HIV-1 is unknown. We examined whether SPL7013 demonstrates virucidal activity against X4 (NL4.3, MBC200, CMU02 clade EA and 92UG046 clade D), R5 (Ba-L, NB25 and 92RW016 clade A) and dual-tropic (R5X4; MACS1-spln) HIV-1 using a modified HLA-DR viral capture method and by polyethylene glycol precipitation. Evaluation of virion integrity was determined by ultracentrifugation through a sucrose cushion and detection of viral proteins by Western blot analysis. SPL7013 demonstrated potent virucidal activity against X4 and R5X4 strains, although virucidal activity was less potent for the 92UG046 X4 clade D isolate. Where potent virucidal activity was observed, the 50 virucidal concentrations were similar to the 50 effective concentrations previously reported in drug susceptibility assays, indicating that the main mode of action of SPL7013 is by direct viral inactivation for these strains....",
author = "Sushama Telwatte and Katie Moore and Adam Johnson and David Tyssen and Jasminka Sterjovski and Muriel Aldunate and Gorry, {Paul R} and Paul Ramsland and Gareth Lewis and Jeremy Paull and Secondo Sonza and Gilda Tachedjian",
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Telwatte, S, Moore, K, Johnson, A, Tyssen, D, Sterjovski, J, Aldunate, M, Gorry, PR, Ramsland, P, Lewis, G, Paull, J, Sonza, S & Tachedjian, G 2011, 'Virucidal activity of the dendrimer microbicide SPL7013 against HIV-1', Antiviral Research, vol. 90, no. 3, pp. 195 - 199. https://doi.org/10.1016/j.antiviral.2011.03.186

Virucidal activity of the dendrimer microbicide SPL7013 against HIV-1. / Telwatte, Sushama; Moore, Katie; Johnson, Adam; Tyssen, David; Sterjovski, Jasminka; Aldunate, Muriel; Gorry, Paul R; Ramsland, Paul; Lewis, Gareth; Paull, Jeremy; Sonza, Secondo; Tachedjian, Gilda.

In: Antiviral Research, Vol. 90, No. 3, 2011, p. 195 - 199.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Virucidal activity of the dendrimer microbicide SPL7013 against HIV-1

AU - Telwatte, Sushama

AU - Moore, Katie

AU - Johnson, Adam

AU - Tyssen, David

AU - Sterjovski, Jasminka

AU - Aldunate, Muriel

AU - Gorry, Paul R

AU - Ramsland, Paul

AU - Lewis, Gareth

AU - Paull, Jeremy

AU - Sonza, Secondo

AU - Tachedjian, Gilda

PY - 2011

Y1 - 2011

N2 - Topical microbicides for use by women to prevent the transmission of human immunodeficiency virus (HIV) and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. SPL7013 is a dendrimer with broad-spectrum activity against HIV type I (HIV-1) and -2 (HIV-2), herpes simplex viruses type-1 (HSV-1) and -2 (HSV-2) and human papillomavirus. SPL7013 [3 (w/w)] has been formulated in a mucoadhesive carbopol gel (VivaGel(R)) for use as a topical microbicide. Previous studies showed that SPL7013 has similar potency against CXCR4-(X4) and CCR5-using (R5) strains of HIV-1 and that it blocks viral entry. However, the ability of SPL7013 to directly inactivate HIV-1 is unknown. We examined whether SPL7013 demonstrates virucidal activity against X4 (NL4.3, MBC200, CMU02 clade EA and 92UG046 clade D), R5 (Ba-L, NB25 and 92RW016 clade A) and dual-tropic (R5X4; MACS1-spln) HIV-1 using a modified HLA-DR viral capture method and by polyethylene glycol precipitation. Evaluation of virion integrity was determined by ultracentrifugation through a sucrose cushion and detection of viral proteins by Western blot analysis. SPL7013 demonstrated potent virucidal activity against X4 and R5X4 strains, although virucidal activity was less potent for the 92UG046 X4 clade D isolate. Where potent virucidal activity was observed, the 50 virucidal concentrations were similar to the 50 effective concentrations previously reported in drug susceptibility assays, indicating that the main mode of action of SPL7013 is by direct viral inactivation for these strains....

AB - Topical microbicides for use by women to prevent the transmission of human immunodeficiency virus (HIV) and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. SPL7013 is a dendrimer with broad-spectrum activity against HIV type I (HIV-1) and -2 (HIV-2), herpes simplex viruses type-1 (HSV-1) and -2 (HSV-2) and human papillomavirus. SPL7013 [3 (w/w)] has been formulated in a mucoadhesive carbopol gel (VivaGel(R)) for use as a topical microbicide. Previous studies showed that SPL7013 has similar potency against CXCR4-(X4) and CCR5-using (R5) strains of HIV-1 and that it blocks viral entry. However, the ability of SPL7013 to directly inactivate HIV-1 is unknown. We examined whether SPL7013 demonstrates virucidal activity against X4 (NL4.3, MBC200, CMU02 clade EA and 92UG046 clade D), R5 (Ba-L, NB25 and 92RW016 clade A) and dual-tropic (R5X4; MACS1-spln) HIV-1 using a modified HLA-DR viral capture method and by polyethylene glycol precipitation. Evaluation of virion integrity was determined by ultracentrifugation through a sucrose cushion and detection of viral proteins by Western blot analysis. SPL7013 demonstrated potent virucidal activity against X4 and R5X4 strains, although virucidal activity was less potent for the 92UG046 X4 clade D isolate. Where potent virucidal activity was observed, the 50 virucidal concentrations were similar to the 50 effective concentrations previously reported in drug susceptibility assays, indicating that the main mode of action of SPL7013 is by direct viral inactivation for these strains....

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U2 - 10.1016/j.antiviral.2011.03.186

DO - 10.1016/j.antiviral.2011.03.186

M3 - Article

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JO - Antiviral Research

JF - Antiviral Research

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Telwatte S, Moore K, Johnson A, Tyssen D, Sterjovski J, Aldunate M et al. Virucidal activity of the dendrimer microbicide SPL7013 against HIV-1. Antiviral Research. 2011;90(3):195 - 199. https://doi.org/10.1016/j.antiviral.2011.03.186