Development and evaluation of a host-targeted antiviral that abrogates herpes simplex virus replication through modulation of arginine-associated metabolic pathways.
Level 5 - mechanism / opinion, no new human data
In vitro laboratory study evaluating antiviral activity in cell culture.
PubMed 27192555 · doi:10.1016/j.antiviral.2016.05.009
What was done
The authors engineered a pegylated recombinant human Arginase I (peg-ArgI) to deplete extracellular arginine and disrupt host metabolic pathways required for viral replication. They evaluated its in vitro antiviral activity against HSV-1, HSV-2, and single- or multidrug-resistant HSV-1 mutant strains, measuring cell viability over 48 hours of continuous exposure, dose-response relationships, viral replication, infectious virion production, cell-to-cell spread, and viral cytopathic effects.
What was found
Continuous peg-ArgI treatment for over 48 hours caused no detectable cytotoxicity or loss of host cell viability. peg-ArgI produced dose-dependent inhibition of HSV-1 and HSV-2 with IC50 values in the sub-nanomolar range (specific numerical values not reported in the abstract). The compound inhibited viral replication, infectious virus yield, cell-to-cell spread, and cytopathology across wild-type viruses as well as single- and multidrug-resistant HSV-1 mutants.
Why it matters
Targeting host metabolic dependence on arginine presents a potential host-directed therapeutic approach that bypasses viral mutations causing resistance to traditional direct-acting antivirals.
Limits
The study was conducted strictly in vitro; in vivo safety, pharmacokinetics, tissue penetrance, and antiviral efficacy remain unknown. The abstract does not report specific numerical IC50 values, confidence intervals, or the specific cell lines tested.
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