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Synthetic Melanins with Antiviral Activity

Enveloped viruses can cause severe, and occasionally life‐threatening, infections in humans and animals. We have prepared a family of water‐soluble synthetic melanin polymers that have differing physicochemical properties and distinctive selectivities for preventing the infection of animal cells by enveloped viruses in vitro. For example, our series of 20 compounds with anti‐HIV activity have been shown to have ED50's in the range of 4 to 216 ng/mL (http://www.bioactivepolymers.com ). Recently we submitted 10 synthetic melanins to the NIAID's Antimicrobial Acquisition and Coordinating Facility for in vitro activity testing against 7 herpesviruses, 7 respiratory viruses, 2 orthopoxviruses, and 10 bioterrorism viruses. The compounds were tested for inhibitory activity using the NIAID's standard screening screening assays as described on their website (http://niaid‐aacf.org/screeningassays.htm ). The results showed that the most potent of our synthetic compounds had the following ED50's (μg/mL) for the 20 viruses tested thus far: HSV1, 1.4; HSV2, 0.06; CMV, 3.4; VZV, < 0.03; EBV, 98; Dengue C., 26; Rift Valley Fever, 26; Tacribe, 41; RSV A., 32; Cowpox, 27; Vaccinia, 10; SARS, 13; H1N1, 2.5; H3N2, 3.2; H5N1, 0 .21; Flu B, 2.0. ED50's of > 100 μg/mL were observed for Yellow Fever, Adenovirus, PIV, and Rhinovirus. The inhibitory activities of screen‐positive compounds with moderate to high activities were confirmed by supplementary testing. The compounds typically had low toxicities toward animal cells, with CC50's of >100 μg/mL. The results suggest that synthetic melanins are promising candidates for the development of topical microbicides for use in the prevention of STD's and for use in the prevention and treatment of other viral infections in humans and animals.