Hudu Shuaibu A, Alshrari Ahmed S, Al Qtaitat Aiman, Imran Mohd
Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan.
Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia.
Biomedicines. 2023 Apr 6;11(4):1106. doi: 10.3390/biomedicines11041106.
Monkeypox disease (Mpox) has threatened humankind worldwide since mid-2022. The Mpox virus (MpoxV) is an example of Orthopoxviruses (OPVs), which share similar genomic structures. A few treatments and vaccines are available for Mpox. OPV-specific VP37 protein (VP37P) is a target for developing drugs against Mpox and other OPV-induced infections such as smallpox. This review spotlights the existing and prospective VP37P inhibitors (VP37PIs) for Mpox. The non-patent literature was collected from PubMed, and the patent literature was gathered from free patent databases. Very little work has been carried out on developing VP37PIs. One VP37PI (tecovirimat) has already been approved in Europe to treat Mpox, while another drug, NIOCH-14, is under clinical trial. Developing tecovirimat/NIOCH-14-based combination therapies with clinically used drugs demonstrating activity against Mpox or other OPV infections (mitoxantrone, ofloxacin, enrofloxacin, novobiocin, cidofovir, brincidofovir, idoxuridine, trifluridine, vidarabine, fialuridine, adefovir, imatinib, and rifampicin), immunity boosters (vitamin C, zinc, thymoquinone, quercetin, ginseng, etc.), and vaccines may appear a promising strategy to fight against Mpox and other OPV infections. Drug repurposing is also a good approach for identifying clinically useful VP37PIs. The dearth in the discovery process of VP37PIs makes it an interesting area for further research. The development of the tecovirimat/NIOCH-14-based hybrid molecules with certain chemotherapeutic agents looks fruitful and can be explored to obtain new VP37PI. It would be interesting and challenging to develop an ideal VP37PI concerning its specificity, safety, and efficacy.
自2022年年中以来，猴痘疾病（Mpox）已在全球范围内威胁人类。猴痘病毒（MpoxV）是正痘病毒（OPV）的一种，它们具有相似的基因组结构。目前有一些针对猴痘的治疗方法和疫苗。OPV特异性的VP37蛋白（VP37P）是开发抗猴痘及其他OPV引起的感染（如天花）药物的靶点。本综述重点介绍了现有的和未来可能用于猴痘的VP37P抑制剂（VP37PI）。非专利文献从PubMed收集，专利文献从免费专利数据库收集。在开发VP37PI方面开展的工作很少。一种VP37PI（特考韦瑞）已在欧洲获批用于治疗猴痘，而另一种药物NIOCH-14正在进行临床试验。将特考韦瑞/NIOCH-14与对猴痘或其他OPV感染有活性的临床用药（米托蒽醌、氧氟沙星、恩诺沙星、新生霉素、西多福韦、布林西多福韦、碘苷、三氟尿苷、阿糖腺苷、非拉米夫定、阿德福韦、伊马替尼和利福平）、免疫增强剂（维生素C、锌、百里醌、槲皮素、人参等）以及疫苗联合使用，可能是对抗猴痘和其他OPV感染的一种有前景的策略。药物再利用也是识别临床上有用的VP37PI的好方法。VP37PI发现过程中的匮乏使其成为一个值得进一步研究的有趣领域。开发基于特考韦瑞/NIOCH-14的与某些化疗药物的杂合分子看起来很有成效，可以探索以获得新的VP37PI。开发一种在特异性、安全性和有效性方面理想的VP37PI将既有趣又具有挑战性。
