Home Acta Virologica 2019 Acta Virologica Vol.63, No.3, p.309-315, 2019

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Quarterly, 72-88 pp. per issue
Founded: 1957
ISSN 0001-723X
E-ISSN 1336-2305

Published in English

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Acta Virologica Vol.63, No.3, p.309-315, 2019

Title: Growth activation of influenza virus by trypsin and effect of T-705 (favipiravir) on trypsin-optimized growth condition
Author: T. DAIKOKU, T. OKUDA, M. KAWAI, N. MORITA, T. TANAKA, M. TAKEMOTO, Y. FUKUDA, K. TAKAHASHI, N. NOMURA, K. SHIRAKI

Abstract: Influenza virus is activated by proteolytic cleavage of hemagglutinin by trypsin. After determining the optimal trypsin concentration, intracellular and extracellular influenza A/PR/8/34 (H1N1) and A/Victoria/361/2011 (H3N2) virus productions were compared in cultures treated with T-705 (favipiravir) and GS 4071 (an active form of oseltamivir). Although both drugs efficiently inhibited extracellular viral RNA release in a dose-dependent manner, T-705 inhibited it to the level of the inoculum without trypsin treatment, while GS 4071 inhibited it to a final level 10 times higher than that without trypsin. T-705 inhibited intracellular viral RNA production to the level of input virus in both trypsin-treated and untreated cells. In contrast, GS 4071 dose-dependently inhibited intracellular viral RNA production in cells treated with trypsin but allowed viral RNA synthesis. The level of maximum inhibition by GS 4071was 10 times higher than that of cells without trypsin and 1,000 times greater than the inoculum titer in cells without trypsin. T-705 inhibited both intracellular and extracellular virus production 1,000 and 10 times more strongly, respectively, than GS 4071. T-705 has powerful anti-influenza activity in the absence of trypsin and even in the trypsin-optimized growth condition, suggesting the therapeutic advantage in treatment of influenza complicated with bacterial pneumonia.

Keywords: influenza; T-705; Tamiflu; trypsin; bacterial trypsin-like protease
Published online: 09-Sep-2019
Year: 2019, Volume: 63, Issue: 3 Page From: 309, Page To: 315
doi:10.4149/av_2019_311
Price: 16.80 €






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