T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has been found to have potent and selective inhibitory activity against influenza virus. In an in vitro plaque reduction assay, T-705 showed potent inhibitory activity against influenza A, B, and C viruses, with 50% inhibitory concentrations (IC 50 s) of 0.013 to 0.48 g/ml, while it showed no cytotoxicity at concentrations up to 1,000 g/ml in Madin-Darby canine kidney cells. The selectivity index for influenza virus was more than 2,000. It was also active against a neuraminidase inhibitorresistant virus and some amantadine-resistant viruses. T-705 showed weak activity against non-influenza virus RNA viruses, with the IC 50 s being higher for non-influenza virus RNA viruses than for influenza virus, and it had no activity against DNA viruses. Orally administered T-705 at 100 mg/kg of body weight/day (four times a day) for 5 days significantly reduced the mean pulmonary virus yields and the rate of mortality in mice infected with influenza virus A/PR/8/34 (3 ؋ 10 2 PFU). These results suggest that T-705 may be a compound that is useful and highly selective against influenza virus infections and that has a mode of action different from those of commercially available drugs, such as amantadine, rimantadine, and neuraminidase inhibitors.

T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has a potent and selective inhibitory activity against influenza virus. We studied the effects of an infectious dose on the anti-influenza virus activities of T-705 and oseltamivir, a commercially available neuraminidase inhibitor, both in vitro and in vivo. Plaque formation of influenza A/PR/8/34 virus was completely inhibited by 10 µg/ml of T-705 after 72 h incubation, whereas visible plaque formation was detected in the plate treated with GS 4071, the active form of oseltamivir (10 µg/ml). The antiviral activity of T-

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Our results suggest that decreased bactericidal activity, or the in vitro PAE of carbapenems and fluoroquinolones, is related to the reduced in vivo protective effect against infection caused by high inoculum with S. aureus or P. aeruginosa.

We compared the short-term outcomes between 3-monthly aflibercept and brolucizumab injections for treatment-naïve polypoidal choroidal vasculopathy (PCV). A total of 52 eyes were included. Patients received 3 monthly intravitreal aflibercept (n = 38) or intravitreal brolucizumab (n = 14). Indocyanine green angiography (ICGA) was performed at baseline and at the 3-month visit. Selection of anti-VEGF agents depended on time. In the brolucizumab-treated group, best-corrected visual acuity (BCVA) improved from 0.27 ± 0.34 (log MAR unit) at baseline to 0.20 ± 0.24 at 3-month visit, which is comparable with the aflibercept-treated group (p = 0.87), after adjustment of confounding factors. Central retinal thickness significantly decreased by 43%−44% in both groups. Subfoveal choroidal thickness also significantly decreased by 20.5% during this interval in the brolucizumab-treated group, which was greater than the aflibercept-treated group. The complete resolution rate of polypoidal lesions on ICGA was significantly higher (p = 0.043) in the brolucizumab-treated group (78.6%) than in the aflibercept-treated group (42.1%). Intraocular inflammation was observed in 14.3% (2/14) in the brolucizumab-treated group only. In short-term follow-up, intravitreal injection of 3-monthly brolucizumab was comparable with aflibercept in terms of BCVA and morphological improvement along with higher resolution of polypoidal lesion(s) on ICGA.