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Sunday, March 15, 2020 4:20:21 AM
A hybrid interferon, IFN-a B/D, and a mismatched dsRNA interferon inducer, Ampligen® (poly I:poly C12U), were the only compounds that potently inhibited virus titers in the lungs of infected mice as assessed by CPE titration assays [104]. Mice were dosed intraperitoneally with IFN-a B/D once-daily for 3 days beginning 4 h after virus exposure, and lung titers reduced by 1 log10 at 10,000 and 32,000 international units compared with lung virus titers in infected, untreated mice. Ampligen used intraperitoneally at 10 mg/kg 4 h prior to virus exposure reduced virus lung titers to below detectable limits. Alferon (human leukocyte IFN-a-n3) did not significantly reduce lung virus titers in mice as would be expected when using human interferon protein to induce mouse antiviral proteins responsive to mouse interferon. The inhibitory activity of Ampligen was later confirmed in a lethal mouse model of SARS-CoV using a mouse-adapted Urbani strain [85]. In that study, all mice survived who were given Ampligen at 10 mg/kg 4 h prior to virus exposure. The lung gross pathology scores at day 6 were significantly lower compared with those for mice treated with placebo (p < 0.05), and the weight loss associated with infection was dramatically reduced (p < 0.001). Interestingly, viral lung titers were not significantly reduced at day 3 or 6 post-virus exposure compared with viral lung titers in the placebo-treated mice. However, by day 6 of the infection, Ampligen treatment led to a more rapid decline of virus detected in the lungs compared with virus detected in the lungs of untreated animals.
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