TY - JOUR
T1 - Tilorone-dihydrochloride protects against rift valley fever virus infection and disease in the mouse model
AU - Johnson, Kendra N.
AU - Kalveram, Birte
AU - Smith, Jennifer K.
AU - Zhang, Lihong
AU - Juelich, Terry
AU - Atkins, Colm
AU - Ikegami, Tetsuro
AU - Freiberg, Alexander N.
N1 - Funding Information:
Funding: This research was partially supported by the National Institutes of Health (NIH) (grant number R33 AI102267 to A.N.F.). K.N.J. was supported by a NIH T32 Biodefense training fellowship (AI060549).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1
Y1 - 2022/1
N2 - Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Middle East that can affect humans and ruminant livestock. Currently, there are no approved vaccines or therapeutics for the treatment of severe RVF disease in humans. Tilorone-dihydrochloride (Tilorone) is a broad-spectrum antiviral candidate that has previously shown efficacy against a wide range of DNA and RNA viruses, and which is clinically utilized for the treatment of respiratory infections in Russia and other Eastern European countries. Here, we evaluated the antiviral activity of Tilorone against Rift Valley fever virus (RVFV). In vitro, Tilorone inhibited both vaccine (MP-12) and virulent (ZH501) strains of RVFV at low micromolar concentrations. In the mouse model, treatment with Tilorone significantly improved survival outcomes in BALB/c mice challenged with a lethal dose of RVFV ZH501. Treatment with 30 mg/kg/day resulted in 80% survival when administered immediately after infection. In post-exposure prophylaxis, Tilorone resulted in 30% survival at one day after infection when administered at 45 mg/kg/day. These findings demonstrate that Tilorone has potent antiviral efficacy against RVFV infection in vitro and in vivo and supports further development of Tilorone as a potential antiviral therapeutic for treatment of RVFV infection.
AB - Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Middle East that can affect humans and ruminant livestock. Currently, there are no approved vaccines or therapeutics for the treatment of severe RVF disease in humans. Tilorone-dihydrochloride (Tilorone) is a broad-spectrum antiviral candidate that has previously shown efficacy against a wide range of DNA and RNA viruses, and which is clinically utilized for the treatment of respiratory infections in Russia and other Eastern European countries. Here, we evaluated the antiviral activity of Tilorone against Rift Valley fever virus (RVFV). In vitro, Tilorone inhibited both vaccine (MP-12) and virulent (ZH501) strains of RVFV at low micromolar concentrations. In the mouse model, treatment with Tilorone significantly improved survival outcomes in BALB/c mice challenged with a lethal dose of RVFV ZH501. Treatment with 30 mg/kg/day resulted in 80% survival when administered immediately after infection. In post-exposure prophylaxis, Tilorone resulted in 30% survival at one day after infection when administered at 45 mg/kg/day. These findings demonstrate that Tilorone has potent antiviral efficacy against RVFV infection in vitro and in vivo and supports further development of Tilorone as a potential antiviral therapeutic for treatment of RVFV infection.
KW - Broad-spectrum antiviral
KW - Bunyavirales
KW - Phenuiviridae
KW - Rift Valley fever virus
KW - Tilorone-dihydrochloride
KW - Viral Hemorrhagic fever
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U2 - 10.3390/microorganisms10010092
DO - 10.3390/microorganisms10010092
M3 - Article
AN - SCOPUS:85122013721
SN - 2076-2607
VL - 10
JO - Microorganisms
JF - Microorganisms
IS - 1
M1 - 92
ER -