TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds

Shiori Haga, Noriyo Nagata, Tadashi Okamura, Norio Yamamoto, Tetsutaro Sata, Naoki Yamamoto, Takehiko Sasazuki, Yukihito Ishizaka

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Because outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV) might reemerge, identifying antiviral compounds is of key importance. Previously, we showed that the cellular factor TNF-α converting enzyme (TACE), activated by the spike protein of SARS-CoV (SARS-S protein), was positively involved in viral entry, implying that TACE is a possible target for developing antiviral compounds. To demonstrate this possibility, we here tested the effects of TACE inhibitors on viral entry. In vitro and in vivo data revealed that the TACE inhibitor TAPI-2 attenuated entry of both pseudotyped virus expressing the SARS-S protein in a lentiviral vector backbone and infectious SARS-CoV. TAPI-2 blocked both the SARS-S protein-induced shedding of angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV, and TNF-α production in lung tissues. Since the downregulation of ACE2 by SARS-S protein was proposed as an etiological event in the severe clinical manifestations, our data suggest that TACE antagonists block SARS-CoV infection and also attenuate its severe clinical outcome.

Original languageEnglish
Pages (from-to)551-555
Number of pages5
JournalAntiviral Research
Volume85
Issue number3
DOIs
Publication statusPublished - Mar 1 2010
Externally publishedYes

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Severe Acute Respiratory Syndrome
Coronavirus
Protein S
SARS Virus
Antiviral Agents
Coronavirus Infections
Proteins
Disease Outbreaks
Down-Regulation
Lung
angiotensin converting enzyme 2
TAPI-2

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

Cite this

TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds. / Haga, Shiori; Nagata, Noriyo; Okamura, Tadashi; Yamamoto, Norio; Sata, Tetsutaro; Yamamoto, Naoki; Sasazuki, Takehiko; Ishizaka, Yukihito.

In: Antiviral Research, Vol. 85, No. 3, 01.03.2010, p. 551-555.

Research output: Contribution to journalArticle

Haga, S, Nagata, N, Okamura, T, Yamamoto, N, Sata, T, Yamamoto, N, Sasazuki, T & Ishizaka, Y 2010, 'TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds', Antiviral Research, vol. 85, no. 3, pp. 551-555. https://doi.org/10.1016/j.antiviral.2009.12.001
Haga, Shiori ; Nagata, Noriyo ; Okamura, Tadashi ; Yamamoto, Norio ; Sata, Tetsutaro ; Yamamoto, Naoki ; Sasazuki, Takehiko ; Ishizaka, Yukihito. / TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds. In: Antiviral Research. 2010 ; Vol. 85, No. 3. pp. 551-555.
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