@article{PAR00011900,
  title = {{E}valuation of antiviral efficacy of {R}ibavirin, {A}rbidol, and {T}-705 ({F}avipiravir) in a mouse model for {C}rimean-{C}ongo hemorrhagic fever},
  author = {{O}estereich, {L}. and {R}ieger, {T}. and {N}eumann, {M}. and {B}ernreuther, {C}. and {L}ehmann, {M}. and {K}rasemann, {S}. and {W}urr, {S}. and {E}mmerich, {P}. and de {L}amballerie, {X}avier and {O}lschlager, {S}. and {G}unther, {S}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {M}ice lacking the type {I} interferon receptor ({IFNAR}(-/-) mice) reproduce relevant aspects of {C}rimean-{C}ongo hemorrhagic fever ({CCHF}) in humans, including liver damage. {W}e aimed at characterizing the liver pathology in {CCHF} virus-infected {IFNAR}(-/-) mice by immunohistochemistry and employed the model to evaluate the antiviral efficacy of ribavirin, arbidol, and {T}-705 against {CCHF} virus. {M}ethodology/{P}rincipal {F}indings: {CCHF} virus-infected {IFNAR}(-/-) mice died 2-6 days post infection with elevated aminotransferase levels and high virus titers in blood and organs. {M}ain pathological alteration was acute hepatitis with extensive bridging necrosis, reactive hepatocyte proliferation, and mild to moderate inflammatory response with monocyte/macrophage activation. {V}irus-infected and apoptotic hepatocytes clustered in the necrotic areas. {R}ibavirin, arbidol, and {T}-705 suppressed virus replication in vitro by >= 3 log units ({IC}50 0.6-2.8 mu g/ml; {IC}90 1.2-4.7 mu g/ml). {R}ibavirin [100 mg/(kgxd)] did not increase the survival rate of {IFNAR}(-/-) mice, but prolonged the time to death (p<0.001) and reduced the aminotransferase levels and the virus titers. {A}rbidol [150 mg/(kgxd)] had no efficacy in vivo. {A}nimals treated with {T}-705 at 1 h [15, 30, and 300 mg/(kgxd)] or up to 2 days [300 mg/(kgxd)] post infection survived, showed no signs of disease, and had no virus in blood and organs. {C}o-administration of ribavirin and {T}-705 yielded beneficial rather than adverse effects. {C}onclusions/{S}ignificance: {A}ctivated hepatic macrophages and monocyte-derived cells may play a role in the proinflammatory cytokine response in {CCHF}. {C}lustering of infected hepatocytes in necrotic areas without marked inflammation suggests viral cytopathic effects. {T}-705 is highly potent against {CCHF} virus in vitro and in vivo. {I}ts in vivo efficacy exceeds that of the current standard drug for treatment of {CCHF}, ribavirin.},
  keywords = {},
  booktitle = {},
  journal = {{P}los {N}eglected {T}ropical {D}iseases},
  volume = {8},
  numero = {5},
  pages = {e2804},
  ISSN = {1935-2735},
  year = {2014},
  DOI = {10.1371/journal.pntd.0002804},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00011900},
}