Highly Effective and Safe Polymeric Inhibitors of Herpes Simplex Virus in Vitro and in Vivo.

A series of poly(ethylene glycol)-block-poly(3-(methacryloylamino)propyl trimethylammonium chloride) (PEG-b-PMAPTAC) water-soluble block copolymers consisting of PEG and PMPTAC were obtained by reversible addition-fragmentation chain-transfer (RAFT) polymerization and demonstrated to function as highly effective herpes simplex virus type 1 (HSV-1) inhibitors as shown by in vitro tests (Vero E6 cells) and in vivo experiments (mouse model). Half-maximal inhibitory concentration (IC50) values were determined by quantitative polymerase chain reaction to be 0.36 ± 0.08 µg/mL for the most effective polymer PEG45-b-PMAPTAC52 and 0.84 ± 1.24 µg/mL for the less effective one, PEG45-b-PMAPTAC74. The study performed on the mouse model showed that the polymers protect mice from lethal infection. The polymers are not toxic to the primary human skin fibroblast cells up to the concentration of 100 µg/mL and to the Vero E6 cells up to 500 µg/mL. No systemic or topical toxicity was observed in vivo, even with mice treated with concentrated formulation (100 mg/mL). The mechanistic studies indicated that polymers interacted with the cell and blocked the formation of the entry/fusion complex. Physicochemical and biological properties of PEGx-b-PMAPTACy make them promising drug candidates.

Cat flu: Broad spectrum polymeric antivirals.

Feline herpesvirus type 1 (FHV-1) and feline calicivirus (FCV) are considered as main causes of feline upper respiratory tract disease and the most common clinical manifestations include rhinotracheitis, conjunctivitis, and nasal/facial ulcerations. While the primary infection is relatively mild, secondary infections pose a threat to young or immunocompromised cats and may result in a fatal outcome. In this study, we made an effort to evaluate antiviral potency of poly(sodium 4-styrenesulfonates) (PSSNa) as potent FHV-1 and FCV inhibitors for topical use. Mechanistic studies showed that PSSNa exhibits a different mechanism of action depending on target species. While PSSNa acts directly on FHV-1 particles blocking their interaction with the host's cell and preventing the infection, the antiviral potency against FCV is based on inhibition at late stages of the viral replication cycle. Altogether, PSSNa polymers are promising drug candidates to be used in the treatment and prevention of the viral upper respiratory tract disease (URTD), regardless of the cause.