A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo

作者：Day Craig W; Baric Ralph; Cai Sui Xiong; Frieman Matt; Kumaki Yohichi; Morrey John D; Smee Donald F; Barnard Dale L^*

来源：Virology, 2009, 395(2): 210-222.

DOI：10.1016/j.virol.2009.09.023

• SARS-CoV
• Lethal
• IL-6
• Ribavirin
• Ampligen (TM)
• UDA
• Protease inhibitor
• Cytokine
• Chemokine
• Mouse

Severe acute respiratory syndrome (SARS) is a highly lethal emerging disease caused by coronavirus SARS-CoV. New lethal animal models for SARS were needed to facilitate antiviral research. We adapted and characterized a new strain of SARS-CoV (strain v2163) that was highly lethal in 5- to 6-week-old BALB/c mice. It had nine mutations affecting 10 amino acid residues. Strain v2163 increased IL-1 alpha, IL-6, MIP-1 alpha, MCP-1, and RANTES in mice, and high IL-6 expression correlated with mortality. The infection largely mimicked human disease, but lung pathology lacked hyaline membrane formation. In vitro efficacy against v2163 was shown with known inhibitors of SARS-CoV replication. In v2163-infected mice, Ampligen (TM) Was fully protective, stinging nettle lectin (UDA) was partially protective, ribavirin was disputable and possibly exacerbated disease, and EP128533 was inactive. Ribavirin, UDA, and Ampligen (TM) decreased IL-6 expression. Strain v2163 provided a valuable model for anti-SARS research.

• 出版日期2009-12-20