Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Department of Pharmaceutical Chemistry, DPSRU, New Delhi, India.
Expert Opin Ther Targets. 2023 Jan-Jun;27(6):419-431. doi: 10.1080/14728222.2023.2230361. Epub 2023 Jul 4.
The global Mpox (MPX) disease outbreak caused by the Mpox virus (MPXV) in 2022 alarmed the World Health Organization (WHO) and health regulation agencies of individual countries leading to the declaration of MPX as a Public Health Emergency. Owing to the genetic similarities between smallpox-causing poxvirus and MPXV, vaccine JYNNEOS, and anti-smallpox drugs Brincidofovir and Tecovirimat were granted emergency use authorization by the United States Food and Drug Administration. The WHO also included cidofovir, NIOCH-14, and other vaccines as treatment options.
This article covers the historical development of EUA-granted antivirals, resistance to these antivirals, and the projected impact of signature mutations on the potency of antivirals against currently circulating MPXV. Since a high prevalence of MPXV infections in individuals coinfected with HIV and MPXV, the treatment results among these individuals have been included.
All EUA-granted drugs have been approved for smallpox treatment. These antivirals show good potency against Mpox. However, conserved resistance mutation positions in MPXV and related poxviruses, and the signature mutations in the 2022 MPXV can potentially compromise the efficacy of the EUA-granted treatments. Therefore, MPXV-specific medications are required not only for the current but also for possible future outbreaks.
2022 年，由猴痘病毒（MPXV）引起的全球猴痘（MPX）疾病爆发引起了世界卫生组织（WHO）和个别国家卫生监管机构的警惕，导致将 MPX 宣布为公共卫生紧急事件。由于引起天花的正痘病毒和 MPXV 之间存在遗传相似性，美国食品和药物管理局紧急批准了 JYNNEOS 疫苗以及抗天花药物 Brincidofovir 和 Tecovirimat。世界卫生组织还将西多福韦、NIOCH-14 和其他疫苗纳入治疗选择。
本文涵盖了获得 EUA 的抗病毒药物的历史发展、对这些抗病毒药物的耐药性以及特征性突变对目前流行的 MPXV 抗病毒药物效力的预测影响。由于 HIV 和 MPXV 合并感染个体中存在高比例的 MPXV 感染，因此包括了这些个体的治疗结果。
所有获得 EUA 的药物均已获准用于天花治疗。这些抗病毒药物对猴痘具有良好的疗效。然而，MPXV 和相关正痘病毒中的保守耐药突变位置以及 2022 年 MPXV 的特征性突变可能会降低 EUA 批准的治疗方法的疗效。因此，不仅需要针对当前，还需要针对未来可能爆发的情况，提供专门针对 MPXV 的药物。
