Department of Microbiology and Infectious Diseases, University of Veterinary Medicine, Hungária krt. 23-25, 1143 Budapest, Hungary.
Department of Microbiology and Infectious Diseases, University of Veterinary Medicine, Hungária krt. 23-25, 1143 Budapest, Hungary.
Vaccine. 2019 Aug 2;37(33):4663-4672. doi: 10.1016/j.vaccine.2018.01.082. Epub 2018 Feb 17.
Five different compounds were tested for their in vitro inhibitory effect against RABV multiplication in mouse neuroblastoma (N2A) cell line. N2A cells were infected with the fixed RABV strain CVS-11 one hour prior to adding antivirals or their respective combinations. The infectious titre of RABV as well as the quantity of viral RNA was determined in the cell culturing medium after 48 h. All five tested compounds (mouse interferon (IFN)-α and -β, ribavirin, favipiravir (T-705) and sorafenib) reduced viral replication in a concentration-dependent manner: IFN-β and sorafenib both provided 73.71% relative inhibition of viral replication in the highest non-cytotoxic concentration, while ribavirin caused 48.07%, IFN-α caused 44.87% and favipiravir caused 35.25% relative inhibition, respectively. When applied in combination, their antiviral activity was not synergistic, but a pronounced inhibition was detected when IFN-β was combined with sorafenib, ribavirin, or favipiravir. The highest antiviral effect was caused by the combination of IFN-β and sorafenib (77.19% relative inhibition). In other combinations there was an antagonistic effect detected in the reduction of viral replication. The results demonstrate that these compounds can be promising candidates for a potential combination treatment of rabies, noting that some combinations are not favourable in vitro, which makes thorough in vivo studies necessary.
五种不同的化合物在体外被测试了对鼠神经母细胞瘤（N2A）细胞系中 RABV 增殖的抑制作用。N2A 细胞在用固定 RABV 株 CVS-11 感染一小时后加入抗病毒药物或其各自的组合。在 48 小时后，在细胞培养物中测定 RABV 的感染滴度以及病毒 RNA 的量。所有五种测试的化合物（鼠干扰素（IFN）-α 和 -β、利巴韦林、法匹拉韦（T-705）和索拉非尼）以浓度依赖性方式降低病毒复制：IFN-β 和索拉非尼在最高非细胞毒性浓度下均提供 73.71%的相对病毒复制抑制，而利巴韦林导致 48.07%，IFN-α 导致 44.87%，法匹拉韦导致 35.25%的相对抑制。当联合应用时，它们的抗病毒活性不是协同的，但在 IFN-β 与索拉非尼、利巴韦林或法匹拉韦联合应用时，检测到明显的抑制作用。IFN-β 和索拉非尼的组合产生了最高的抗病毒效果（77.19%的相对抑制）。在其他组合中，在降低病毒复制方面检测到拮抗作用。结果表明，这些化合物可能是狂犬病潜在联合治疗的有希望的候选物，需要注意的是，一些组合在体外不利，这使得深入的体内研究成为必要。
