Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
Microbiol Spectr. 2024 Nov 5;12(11):e0139924. doi: 10.1128/spectrum.01399-24. Epub 2024 Oct 15.
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). CP-COV03 is a novel antiviral candidate that significantly enhanced the bioavailability of niclosamide through inorganic-based drug delivery technology. The active pharmaceutical ingredient of CP-COV03, niclosamide, has been previously shown to possess broad-spectrum antiviral activity against over 30 different viruses in the tests. The aim of this study is to confirm the antiviral activity of CP-COV03 against the SFTSV in an model. Vero cells and SFTS viral stock NCCP43270, a 2015 Gangwon Province isolate, were used to obtain the 50% tissue culture infective dose of the virus. Vero cells seeded in 96-well plates were infected with SFTSV for 1 h. SFTSV-infected cells were treated with CP-COV03 at various concentrations of 0.1-100 μM and incubated for 7 days. On the seventh day of the culture, the cytopathic effect (CPE) of SFTSV was checked by microscopy and the cell viability was checked by using Cell Counting Kit-8 assay. The CPE reduced as the CP-COV03 concentration increased. The 50% inhibitory concentration (IC) range of CP-COV03 was below 0.125 µM, as determined from the viral titers of culture supernatants collected on the third day posttreatment of CP-COV03. The plaque reduction assay showed that the IC of CP-COV03 was 1.893 µM, as determined from the percentage reduction of plaque counts for each drug concentration on the second day posttreatment with CP-COV03. This study suggests that CP-COV03 could be used as a potential antiviral agent for SFTS.IMPORTANCEWe demonstrated a concentration-dependent response and identified low a IC of CP-COV03. This result is comparable to other antiviral drugs used against viruses like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We believe that our study makes a significant contribution to the literature as our findings suggest that CP-COV03 may serve as a potential treatment for SFTS, highlighting its importance in the field of antiviral research.
严重发热伴血小板减少综合征(SFTS)是一种由 SFTS 病毒(SFTSV)引起的蜱传传染病。CP-COV03 是一种新型抗病毒候选药物,通过无机药物递送技术显著提高了尼氯硝唑的生物利用度。CP-COV03 的活性药物成分尼氯硝唑先前已被证明对 30 多种不同病毒具有广谱抗病毒活性。本研究旨在确认 CP-COV03 在 SFTSV 感染模型中的抗病毒活性。使用 Vero 细胞和 SFTS 病毒株 NCCP43270(2015 年江原道分离株)获得病毒的 50%组织培养感染剂量。将接种在 96 孔板中的 Vero 细胞用 SFTSV 感染 1 小时。用不同浓度(0.1-100 μM)的 CP-COV03 处理 SFTSV 感染的细胞,并孵育 7 天。在培养的第 7 天,通过显微镜检查 SFTSV 的细胞病变效应(CPE),并通过 Cell Counting Kit-8 测定法检查细胞活力。随着 CP-COV03 浓度的增加,CPE 减少。从 CP-COV03 处理后第 3 天收集的培养上清液中的病毒滴度确定,CP-COV03 的 50%抑制浓度(IC)范围低于 0.125 μM。噬斑减少测定表明,从 CP-COV03 处理后第 2 天每个药物浓度的噬斑数减少百分比确定,CP-COV03 的 IC 为 1.893 μM。本研究表明 CP-COV03 可用作 SFTS 的潜在抗病毒药物。
重要性:
我们观察到 CP-COV03 呈浓度依赖性反应,并确定了低 IC。这一结果与用于治疗严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)等病毒的其他抗病毒药物相当。我们相信我们的研究对文献做出了重要贡献,因为我们的发现表明 CP-COV03 可能成为 SFTS 的潜在治疗方法,突出了其在抗病毒研究领域的重要性。