Wang Pengcheng, Wang Xianwei, Liu Xing, Sun Meng, Liang Xiao, Bai Juan, Jiang Ping
Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
Front Pharmacol. 2022 May 4;13:879733. doi: 10.3389/fphar.2022.879733. eCollection 2022.
Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus (α-CoV) that causes high mortality in suckling piglets, leading to severe economic losses worldwide. No effective vaccine or commercial antiviral drug is readily available. Several replicative enzymes are responsible for coronavirus replication. In this study, the potential candidates targeting replicative enzymes (PLP2, 3CLpro, RdRp, NTPase, and NendoU) were screened from 187,119 compounds in ZINC natural products library, and seven compounds had high binding potential to NTPase and showed drug-like property. Among them, ZINC12899676 was identified to significantly inhibit the NTPase activity of PEDV by targeting its active pocket and causing its conformational change, and ZINC12899676 significantly inhibited PEDV replication in IPEC-J2 cells. It first demonstrated that ZINC12899676 inhibits PEDV replication by targeting NTPase, and then, NTPase may serve as a novel target for anti-PEDV.
猪流行性腹泻病毒（PEDV）是一种甲型冠状病毒（α-CoV），可导致哺乳仔猪的高死亡率，在全球范围内造成严重的经济损失。目前尚无有效的疫苗或商用抗病毒药物。几种复制酶负责冠状病毒的复制。在本研究中，从ZINC天然产物库中的187,119种化合物中筛选了针对复制酶（PLP2、3CLpro、RdRp、NTPase和NendoU）的潜在候选物，其中7种化合物对NTPase具有高结合潜力并表现出类药物特性。其中，ZINC12899676被鉴定为通过靶向其活性口袋并引起其构象变化来显著抑制PEDV的NTPase活性，并且ZINC12899676在IPEC-J2细胞中显著抑制PEDV复制。首次证明ZINC12899676通过靶向NTPase抑制PEDV复制，因此，NTPase可能作为抗PEDV的新靶点。
