The Proteasome Inhibitor Velcade Enhances rather than Reduces Disease in Mouse Hepatitis Coronavirus-Infected Mice
The Proteasome Inhibitor Velcade Enhances rather than Reduces Disease in Mouse Hepatitis Coronavirus-Infected Mice
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DOI：
10.1128/jvi.00486-10
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发表时间：
2010-08-01
影响因子：
5.4
通讯作者：
de Haan, Cornelis A. M.
中科院分区：
文献类型：
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作者：
Raaben, Matthijs;Grinwis, Guy C. M.;de Haan, Cornelis A. M.
许多病毒，包括冠状病毒(CoV)，依赖于功能正常的细胞蛋白酶体在体外有效地感染。因此，蛋白酶体抑制剂VELCADE(Bortezomib)，一种临床批准的抗癌药物，在一项伴随的研究中显示(M.Raaben等人，J.Virol。84：7869-7879,2010)在培养细胞中强烈抑制小鼠肝炎冠状病毒(MHV)感染，似乎是在体内测试其抗病毒性能的有吸引力的候选药物。然而，令人惊讶的是，这种药物并没有减少病毒在老鼠体内的复制。相反，抑制蛋白酶体会导致感染加剧，结果是致命的，呼吁在感染期间使用这种药物时要谨慎。
Many viruses, including coronaviruses (CoVs), depend on a functional cellular proteasome for efficient infection in vitro. Hence, the proteasome inhibitor Velcade (bortezomib), a clinically approved anticancer drug, shown in an accompanying study (M. Raaben et al., J. Virol. 84: 7869-7879, 2010) to strongly inhibit mouse hepatitis CoV (MHV) infection in cultured cells, seemed an attractive candidate for testing its antiviral properties in vivo. Surprisingly, however, the drug did not reduce replication of the virus in mice. Rather, inhibition of the proteasome caused enhanced infection with lethal outcome, calling for caution when using this type of drug during infection.