The effect of combined drugs therapy on the course of clinical rabies infection in a murine model. Issue 33 (2nd August 2019)

• Record Type: Journal Article
• Authors: Smreczak, Marcin; Orłowska, Anna; Marzec, Anna; Trębas, Paweł; Kycko, Anna; Reichert, Michał; Koraka, Penelope; Osterhaus, Albert D.M.E.; Żmudziński, Jan Franciszek
• Is Part Of: Vaccine. Volume 37:Issue 33(2019)
• Page Start: 4701
• Page End: 4709
• Publication Date: 2019-08-02
• Subjects: Clinical rabies -- SHBRV-18 -- Antivirals -- Host immune response modulators -- Interferon α/β; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2018.04.003
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Beneficial results of using drug combination therapy. Influence of using of INFα/β on rabies infection. Extended of mice survival by inhibiting of RV replication. Abstract: Rabies is a fatal disease of all mammals causing almost 60, 000 human deaths every year. To date, there is no effective treatment of clinical rabies once the symptoms appear. Here, we describe the promising effect of combination therapy composed of molecules that target replication of the rabies virus (RV) at different stages of life cycle and molecules that inhibit some pathways of the innate host immune response accompanied by a blood-brain barrier opener on the outcome of RV infection. The study reports statistically significant extension of survival of mice treated with the drug cocktail containing T-705, ribavirin, interferon α/β, caspase-1 inhibitor, TNF-α inhibitor, MAPKs inhibitor and HRIG compared to the survival of mice in the virus control group (p = 0.0312). Furthermore, the study points to the significant impact of interferon α/β on the survival of RV-infected mice. We have shown a significant down regulation of pro-inflammatory molecules (caspase-1 and TNF-a) in the CNS in RV-infected mice treated with a combination of drugs including interferon α/β.