RT Journal Article
SR Electronic
T1 SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 752592
DO 10.1101/752592
A1 Marco R. Straus
A1 Jonathan T. Kinder
A1 Michal Segall
A1 Rebecca Ellis Dutch
A1 Gary R. Whittaker
YR 2020
UL http://biorxiv.org/content/early/2020/01/06/752592.abstract
AB Viruses possessing class I fusion proteins require proteolytic activation by host cell proteases to mediate fusion with the host cell membrane. The mammalian SPINT2 gene encodes a protease inhibitor that targets trypsin-like serine proteases. Here we show the protease inhibitor, SPINT2, restricts cleavage-activation efficiently for a range of influenza viruses and for human metapneumovirus (HMPV). SPINT2 treatment resulted in the cleavage and fusion inhibition of full-length influenza A/CA/04/09 (H1N1) HA, A/Aichi/68 (H3N2) HA, A/Shanghai/2/2013 (H7N9) HA and HMPV F when activated by trypsin, recombinant matriptase or KLK5. We also demonstrate that SPINT2 was able to reduce viral growth of influenza A/CA/04/09 H1N1 and A/X31 H3N2 in cell culture by inhibiting matriptase or TMPRSS2. Moreover, inhibition efficacy did not differ whether SPINT2 was added at the time of infection or 24 hours post-infection. Our data suggest that the SPINT2 inhibitor has a strong potential to serve as a novel broad-spectrum antiviral.