Warner Bryce M, Vendramelli Robert, Boese Amrit S, Audet Jonathan, Tailor Nikesh, Meilleur Courtney, Glowach Nathan, Willman Marnie, Truong Thang, Moffat Estella, Tierney Kevin, Kosak Beata, Dhanidina Irfan, Engstrom Jarret, Korczak Bozena, McGowan Ian, Embury-Hyatt Carissa, Kobasa Darwyn
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.
PLoS One. 2025 Feb 5;20(2):e0316952. doi: 10.1371/journal.pone.0316952. eCollection 2025.
Since the emergence of SARS-CoV-2 and the COVID-19 pandemic, a wide range of treatment options have been evaluated in preclinical studies and clinical trials, with several being approved for use in humans. Immunomodulatory drugs have shown success in dampening the deleterious inflammatory response seen in severe COVID-19 patients, but there remains an urgent need for development of additional therapeutic options for COVID-19 treatment. A potential drug target is the CCR5-CCL5 axis, and blocking this pathway may protect against severe disease. Here we evaluated whether OB-002, an analog of human CCL5 and a potent antagonist of CCR5, provides therapeutic benefit in SARS-CoV-2 infected Syrian hamsters. Daily treatment with OB-002 altered immune gene transcription in the lungs, and reduced pathology following infection, but did not prevent weight loss or viral replication in the lungs of infected animals, even in combination with the antiviral drug remdesivir. Our data suggest that targeting the CCR5-CCL5 pathway in SARS-CoV-2 infection in hamsters is insufficient to significantly impact disease development in this model.
自严重急性呼吸综合征冠状病毒2(SARS-CoV-2)出现及新型冠状病毒肺炎(COVID-19)大流行以来,多种治疗方案已在临床前研究和临床试验中得到评估,其中几种已获批用于人类。免疫调节药物已成功减轻了重症COVID-19患者中出现的有害炎症反应,但仍迫切需要开发更多用于COVID-19治疗的治疗方案。一个潜在的药物靶点是CCR5-CCL5轴,阻断该途径可能预防重症疾病。在此,我们评估了人CCL5类似物且为CCR5强效拮抗剂的OB-002,在感染SARS-CoV-2的叙利亚仓鼠中是否具有治疗益处。用OB-002每日治疗可改变肺部免疫基因转录,并减轻感染后的病理变化,但即使与抗病毒药物瑞德西韦联合使用,也不能防止感染动物肺部体重减轻或病毒复制。我们的数据表明,在仓鼠SARS-CoV-2感染中靶向CCR5-CCL5途径不足以显著影响该模型中的疾病发展。