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Identification of restriction endonuclease with potential ability to cleave the HSV-2 genome: inherent potential for biosynthetic versus live recombinant microbicides.

Wayengera M, Kajumbula H, Byarugaba W - Theor Biol Med Model (2008)

Bottom Line: Developing biomedical strategies for HSV-2 prevention is thus a central strategy in reducing global HIV-1 prevalence.In silico palindromics has a PPV of 99.5% for in situ REase activity (2) Two models detailing how the REase EcoRII may be applied in developing interventions against HSV-2 are presented: a nanoparticle for microbicide development and a "recombinant lactobacillus" expressing cell wall anchored receptor (truncated nectin-1) for HSV-2 plus EcoRII.Viral genome slicing by way of these bacterially- derived R-M enzymatic peptides may have therapeutic potential in HSV-2 infection; a cofactor for HIV-1 acquisition and transmission.

View Article: PubMed Central - HTML - PubMed

Affiliation: Restrizymes Biotherapeutics Uganda Limited, Kampala, Uganda. wmisaki@yahoo.com

ABSTRACT

Background: Herpes Simplex virus types 1 and 2 are enveloped viruses with a linear dsDNA genome of approximately 120-200 kb. Genital infection with HSV-2 has been denoted as a major risk factor for acquisition and transmission of HIV-1. Developing biomedical strategies for HSV-2 prevention is thus a central strategy in reducing global HIV-1 prevalence. This paper details the protocol for the isolation of restriction endunucleases (REases) with potent activity against the HSV-2 genome and models two biomedical interventions for preventing HSV-2.

Methods and results: Using the whole genome of HSV-2, 289 REases and the bioinformatics software Webcutter2; we searched for potential recognition sites by way of genome wide palindromics. REase application in HSV-2 biomedical therapy was modeled concomitantly. Of the 289 enzymes analyzed; 77(26.6%) had potential to cleave the HSV-2 genome in > 100 but < 400 sites; 69(23.9%) in > 400 but < 700 sites; and the 9(3.1%) enzymes: BmyI, Bsp1286I, Bst2UI, BstNI, BstOI, EcoRII, HgaI, MvaI, and SduI cleaved in more than 700 sites. But for the 4: PacI, PmeI, SmiI, SwaI that had no sign of activity on HSV-2 genomic DNA, all 130(45%) other enzymes cleaved < 100 times. In silico palindromics has a PPV of 99.5% for in situ REase activity (2) Two models detailing how the REase EcoRII may be applied in developing interventions against HSV-2 are presented: a nanoparticle for microbicide development and a "recombinant lactobacillus" expressing cell wall anchored receptor (truncated nectin-1) for HSV-2 plus EcoRII.

Conclusion: Viral genome slicing by way of these bacterially- derived R-M enzymatic peptides may have therapeutic potential in HSV-2 infection; a cofactor for HIV-1 acquisition and transmission.

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Related in: MedlinePlus

This figure shows the chemical structures of nonoxynol-9 and C31G. A. Note the hydrophilic end with the hydroxyl ion at the extreme left; and the hydrophobic hydrocarbon-benzene complex. This property confers on this molecule the ability to complex with both hydrophilic (ionized) and hydrophobic molecules. The chemical formula and molecular mass of a single nonoxynol-9 molecule are respectively C33H60O10 and 616.823 g/mol. B. C31G is a 1:1 mixed Micelle of Alkyl dimethyl amine oxide and Alkyl dimethylglycine (betaine).
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Figure 1: This figure shows the chemical structures of nonoxynol-9 and C31G. A. Note the hydrophilic end with the hydroxyl ion at the extreme left; and the hydrophobic hydrocarbon-benzene complex. This property confers on this molecule the ability to complex with both hydrophilic (ionized) and hydrophobic molecules. The chemical formula and molecular mass of a single nonoxynol-9 molecule are respectively C33H60O10 and 616.823 g/mol. B. C31G is a 1:1 mixed Micelle of Alkyl dimethyl amine oxide and Alkyl dimethylglycine (betaine).

Mentions: A model of a nanoparticle that may be explored in microbicide development was conceptualized. We based that conception on the hypothesis that "for viral genome to be rendered susceptible to a REase with potent activity against the HSV-2 genome, the naked HSV-2 genome must be brought into proximity with the REase". For purposes of this modeling, we have theoretically employed chemical two surfactants, Nonoxynol-9 and Savvy (C31G); although several other synthetic detergents with demonstrated safe profiles following repeated application in vaginal mucosa of both humans and animals such as 1.0% Savvy (C31G) [28]; and plant derivative like Praneem polyherbal suppository and gossypol may serve the purpose. Note that meta-analysis of randomized controlled trials including more than 5000 women for N-9 safety have indicated some evidence of harm through genital lesions; with N-9 not being recommended for HIV and STI prevention[29]; while no serious adverse event was attributable to SAVVY(C31G) use by a Phase 3, double-blind, randomized, placebo-controlled trial [30]. To this regard, for purposes of in-vivo viral envelope-disruption, Savvy and other surfactants with safe profiles in humans may be a better and safer option. The chemical structure and molecular weight of both N-9 and Savvy are shown in Figure 1.


Identification of restriction endonuclease with potential ability to cleave the HSV-2 genome: inherent potential for biosynthetic versus live recombinant microbicides.

Wayengera M, Kajumbula H, Byarugaba W - Theor Biol Med Model (2008)

This figure shows the chemical structures of nonoxynol-9 and C31G. A. Note the hydrophilic end with the hydroxyl ion at the extreme left; and the hydrophobic hydrocarbon-benzene complex. This property confers on this molecule the ability to complex with both hydrophilic (ionized) and hydrophobic molecules. The chemical formula and molecular mass of a single nonoxynol-9 molecule are respectively C33H60O10 and 616.823 g/mol. B. C31G is a 1:1 mixed Micelle of Alkyl dimethyl amine oxide and Alkyl dimethylglycine (betaine).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2526989&req=5

Figure 1: This figure shows the chemical structures of nonoxynol-9 and C31G. A. Note the hydrophilic end with the hydroxyl ion at the extreme left; and the hydrophobic hydrocarbon-benzene complex. This property confers on this molecule the ability to complex with both hydrophilic (ionized) and hydrophobic molecules. The chemical formula and molecular mass of a single nonoxynol-9 molecule are respectively C33H60O10 and 616.823 g/mol. B. C31G is a 1:1 mixed Micelle of Alkyl dimethyl amine oxide and Alkyl dimethylglycine (betaine).
Mentions: A model of a nanoparticle that may be explored in microbicide development was conceptualized. We based that conception on the hypothesis that "for viral genome to be rendered susceptible to a REase with potent activity against the HSV-2 genome, the naked HSV-2 genome must be brought into proximity with the REase". For purposes of this modeling, we have theoretically employed chemical two surfactants, Nonoxynol-9 and Savvy (C31G); although several other synthetic detergents with demonstrated safe profiles following repeated application in vaginal mucosa of both humans and animals such as 1.0% Savvy (C31G) [28]; and plant derivative like Praneem polyherbal suppository and gossypol may serve the purpose. Note that meta-analysis of randomized controlled trials including more than 5000 women for N-9 safety have indicated some evidence of harm through genital lesions; with N-9 not being recommended for HIV and STI prevention[29]; while no serious adverse event was attributable to SAVVY(C31G) use by a Phase 3, double-blind, randomized, placebo-controlled trial [30]. To this regard, for purposes of in-vivo viral envelope-disruption, Savvy and other surfactants with safe profiles in humans may be a better and safer option. The chemical structure and molecular weight of both N-9 and Savvy are shown in Figure 1.

Bottom Line: Developing biomedical strategies for HSV-2 prevention is thus a central strategy in reducing global HIV-1 prevalence.In silico palindromics has a PPV of 99.5% for in situ REase activity (2) Two models detailing how the REase EcoRII may be applied in developing interventions against HSV-2 are presented: a nanoparticle for microbicide development and a "recombinant lactobacillus" expressing cell wall anchored receptor (truncated nectin-1) for HSV-2 plus EcoRII.Viral genome slicing by way of these bacterially- derived R-M enzymatic peptides may have therapeutic potential in HSV-2 infection; a cofactor for HIV-1 acquisition and transmission.

View Article: PubMed Central - HTML - PubMed

Affiliation: Restrizymes Biotherapeutics Uganda Limited, Kampala, Uganda. wmisaki@yahoo.com

ABSTRACT

Background: Herpes Simplex virus types 1 and 2 are enveloped viruses with a linear dsDNA genome of approximately 120-200 kb. Genital infection with HSV-2 has been denoted as a major risk factor for acquisition and transmission of HIV-1. Developing biomedical strategies for HSV-2 prevention is thus a central strategy in reducing global HIV-1 prevalence. This paper details the protocol for the isolation of restriction endunucleases (REases) with potent activity against the HSV-2 genome and models two biomedical interventions for preventing HSV-2.

Methods and results: Using the whole genome of HSV-2, 289 REases and the bioinformatics software Webcutter2; we searched for potential recognition sites by way of genome wide palindromics. REase application in HSV-2 biomedical therapy was modeled concomitantly. Of the 289 enzymes analyzed; 77(26.6%) had potential to cleave the HSV-2 genome in > 100 but < 400 sites; 69(23.9%) in > 400 but < 700 sites; and the 9(3.1%) enzymes: BmyI, Bsp1286I, Bst2UI, BstNI, BstOI, EcoRII, HgaI, MvaI, and SduI cleaved in more than 700 sites. But for the 4: PacI, PmeI, SmiI, SwaI that had no sign of activity on HSV-2 genomic DNA, all 130(45%) other enzymes cleaved < 100 times. In silico palindromics has a PPV of 99.5% for in situ REase activity (2) Two models detailing how the REase EcoRII may be applied in developing interventions against HSV-2 are presented: a nanoparticle for microbicide development and a "recombinant lactobacillus" expressing cell wall anchored receptor (truncated nectin-1) for HSV-2 plus EcoRII.

Conclusion: Viral genome slicing by way of these bacterially- derived R-M enzymatic peptides may have therapeutic potential in HSV-2 infection; a cofactor for HIV-1 acquisition and transmission.

Show MeSH
Related in: MedlinePlus