Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, 30329, USA.
Prosetta Biosciences, 670 5th Street, San Francisco, CA, 94107, USA.
Antiviral Res. 2021 Jul;191:105086. doi: 10.1016/j.antiviral.2021.105086. Epub 2021 May 13.
Decades after the eradication of smallpox and the discontinuation of routine smallpox vaccination, over half of the world's population is immunologically naïve to variola virus and other orthopoxviruses (OPXVs). Even in those previously vaccinated against smallpox, protective immunity wanes over time. As such, there is a concomitant increase in the incidence of human OPXV infections worldwide. To identify novel antiviral compounds with potent anti-OPXV potential, we characterized the inhibitory activity of PAV-866 and other methylene blue derivatives against the prototypic poxvirus, vaccinia virus (VACV). These compounds inactivated virions prior to infection and consequently inhibited viral binding, fusion and entry. The compounds exhibited strong virucidal activity at non-cytotoxic concentrations, and inhibited VACV infection when added before, during or after viral adsorption. The compounds were effective against other OPXVs including monkeypox virus, cowpox virus and the newly identified Akhmeta virus. Altogether, these findings reveal a novel mode of inhibition that has not previously been demonstrated for small molecule compounds against VACV. Additional studies are in progress to determine the in vivo efficacy of these compounds against OPXVs and further characterize the anti-viral effects of these derivatives.
在消灭天花和停止常规天花疫苗接种几十年后，世界上超过一半的人口对天花病毒和其他正痘病毒（OPXVs）在免疫上是幼稚的。即使是那些以前接种过天花疫苗的人，保护性免疫力也会随着时间的推移而减弱。因此，全世界 OPXV 感染的发病率相应增加。为了确定具有强大抗 OPXV 潜力的新型抗病毒化合物，我们对 PAV-866 和其他亚甲蓝衍生物对典型痘病毒——牛痘病毒（VACV）的抑制活性进行了表征。这些化合物在感染前使病毒失活，从而抑制病毒结合、融合和进入。这些化合物在非细胞毒性浓度下表现出很强的病毒杀伤活性，并在病毒吸附前、吸附时和吸附后加入时抑制 VACV 感染。这些化合物对其他 OPXV 有效，包括猴痘病毒、牛痘病毒和新发现的阿克赫梅塔病毒。总之，这些发现揭示了一种以前从未针对 VACV 的小分子化合物证明的新型抑制模式。正在进行额外的研究以确定这些化合物对 OPXV 的体内疗效，并进一步表征这些衍生物的抗病毒作用。
