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.