卡波西肉瘤相关疱疹病毒 (KSHV) 是原发性渗出性淋巴瘤 (PEL)、多中心卡斯尔曼病 (MCD) 和卡波西肉瘤 (KS) 的病原体。 KSHV 是每年导致 150 万新感染相关癌症病例的肿瘤病毒之一。目前，尚无针对 KSHV 相关疾病的靶向治疗方法。通过开发基于 KSHV ORF57 蛋白检测的中等通量表型 ELISA 筛选平台，我们筛选了 Medicines for Malaria Venture (MMV) 大流行应对盒中 KSHV 裂解复制的非细胞毒性抑制剂。 MMV1645152 被认为是一种很有前途的 KSHV 裂解复制抑制剂，可抑制 KSHV 早期和晚期裂解基因表达，并在有或没有 EBV 共感染的 KSHV 感染细胞系模型中以非细胞毒性浓度阻断感染性 KSHV 病毒粒子的产生。 MMV1645152 是一种很有前途的热门化合物，可用于开发未来针对 KSHV 相关恶性肿瘤的治疗药物。版权所有 © 2024。由 Elsevier B.V. 出版。

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent for primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD) and Kaposi's sarcoma (KS). KSHV is one of the oncoviruses that contribute to 1.5 million new infection-related cancer cases annually. Currently, there are no targeted therapies for KSHV-associated diseases. Through the development of a medium-throughput phenotype-based ELISA screening platform based on KSHV ORF57 protein detection, we screened the Medicines for Malaria Venture (MMV) Pandemic Response Box for non-cytotoxic inhibitors of KSHV lytic replication. MMV1645152 was identified as a promising inhibitor of KSHV lytic replication, suppressing KSHV immediate-early and late lytic gene expression and blocking the production of infectious KSHV virion particles at non-cytotoxic concentrations in cell line models of KSHV infection with or without EBV coinfection. MMV1645152 is a promising hit compound for the development of future therapeutic agents against KSHV-associated malignancies.Copyright © 2024. Published by Elsevier B.V.