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

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-1alpha, IL-6, MIP-1alpha, 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 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 decreased IL-6 expression. Strain v2163 provided a valuable model for anti-SARS research.

Medienart:

E-Artikel

Erscheinungsjahr:

2009

Erschienen:

2009

Enthalten in:

Zur Gesamtaufnahme - volume:395

Enthalten in:

Virology - 395(2009), 2 vom: 20. Dez., Seite 210-22

Sprache:

Englisch

Beteiligte Personen:

Day, Craig W [VerfasserIn]
Baric, Ralph [VerfasserIn]
Cai, Sui Xiong [VerfasserIn]
Frieman, Matt [VerfasserIn]
Kumaki, Yohichi [VerfasserIn]
Morrey, John D [VerfasserIn]
Smee, Donald F [VerfasserIn]
Barnard, Dale L [VerfasserIn]

Links:

Volltext

Themen:

Antiviral Agents
Cytokines
Journal Article
Research Support, N.I.H., Extramural
Viral Proteins

Anmerkungen:

Date Completed 23.12.2009

Date Revised 28.02.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.virol.2009.09.023

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM192266667