Mechanism of Action of T-705 against Influenza Virus

T-705, a substituted pyrazine compound, has been found to exhibit potent anti-influenza virus activity in vitro and in vivo. In a time-of-addition study, it was indicated that T-705 targeted an early to middle stage of the viral replication cycle but had no effect on the adsorption or release stage. The anti-influenza virus activity of T-705 was attenuated by addition of purines and purine nucleosides, including adenosine, guanosine, inosine, and hypoxanthine, whereas pyrimidines did not affect its activity. T-705-4-ribofuranosyl-5′-triphosphate (T-705RTP) and T-705-4-ribofuranosyl-5′-monophosphate (T-705RMP) were detected in MDCK cells treated with T-705. T-705RTP inhibited influenza virus RNA polymerase activity in a dose-dependent and a GTP-competitive manner. Unlike ribavirin, T-705 did not have an influence on cellular DNA or RNA synthesis. Inhibition of cellular IMP dehydrogenase by T-705RMP was about 150-fold weaker than that by ribavirin monophosphate, indicating the specificity of the anti-influenza virus activity and lower level of cytotoxicity of T-705. These results suggest that T-705RTP, which is generated in infected cells, may function as a specific inhibitor of influenza virus RNA polymerase and contributes to the selective anti-influenza virus activity of T-705

Recent Progress at KEKB

We summarize the machine operation of KEKB during past one year. Progress for this period, causes of present performance limitations and future prospects are described

The SuperKEKB Has Broken the World Record of the Luminosity

The SuperKEKB broke the world record of the luminosity in June 2020 in the Phase 3 operation. The luminosity has been increasing since then and the present highest luminosity is 4.65 x 10³⁴ cm⁻²s⁻¹ with β_{y}^{*} of 1 mm. The increase of the luminosity was brought with an application of crab waist, by increasing beam currents and by other improvements in the specific luminosity. In this paper, we describe what we have achieved and what we are struggling with. Finally, we mention a future plan briefly