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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the COVID-19 pandemic, is rapidly evolving. Due to the limited efficacy of vaccination in prevention of SARS-CoV-2 transmission and continuous emergence of variants of concern (VOC), including the currently most prevalent Delta variant, orally bioavailable and broadly efficacious antiviral drugs are urgently needed. Previously we showed that adenosine analogue 69-0 (also known as GS-441524), possesses potent anti-SARS-CoV-2 activity. Herein, we report that esterification of the 5-hydroxyl moieties of 69-0 markedly improved the antiviral potency. The 5-hydroxyl-isobutyryl prodrug, ATV006, showed excellent oral bioavailability in rats and cynomolgus monkeys and potent antiviral efficacy against different VOCs of SARS-CoV-2 in cell culture and three mouse models. Oral administration of ATV006 significantly reduced viral loads, alleviated lung damage and rescued mice from death in the K18-hACE2 mouse model challenged with the Delta variant. Moreover, ATV006 showed broad antiviral efficacy against different mammal-infecting coronaviruses. These indicate that ATV006 represents a promising oral drug candidate against SARS-CoV-2 VOCs and other coronaviruses.
RESUMEN
Objective To determine the content of taurine in Mactra veneriformis by pre-column derivation HPLC.Methods Ultrasound method was used for the extraction of taurine from Mactra veneriformis.In alkaline condition,amino acids reacted with phenyl isothiocyanate and resulted in the derivatives of benzene isothiocyanate-amino acid complex.Kromasil C18 column(4.6 mm ?250 mm,5 ?m) was used and the absorbance at 254 nm was measured.The mobile phase consisted of sodium acetate solution,water and methanol.Results Corresponding chromatographic peaks of taurine were obtained in extract sample and the control.The linear range of taurine was from 10.04 ?g?mL-1 to 50.20 ?g?mL-1,and the recovery was 97.95 %(RSD=1.41%,n=9).Conclusion This method is simple,accurate and reproducible.The seasonal variation range of taurine level is from 10.56 mg/g to 20.91 mg/g,and the taurine level arrived to the peak in June.
