Cenicriviroc (CVC) is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors[1].
Cenicriviroc is a small-molecule chemokine receptor antagonist with highly potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity through antagonizing CCR5 as a coreceptor of HIV-1. Cenicriviroc also strongly antagonizes CCR2b, thereby it has potent anti-inflammatory and immunomodulatory effects[2].
Cenicriviroc is a selective inhibitor of SARS-CoV-2 replication.When VeroE6/TMPRSS2 cells were infected with SARS-CoV-2 and incubated in the absence of compounds for 3 days, the cells were completely destroyed by the virus-induced cytopathic effect (Fig. 1 B). Such cell destruction was not observed for the infected cells in the presence of 20 μM Cenicriviroc, although some morphological changes were identified[3].
Repeated intrathecal injections of Cenicriviroc in a dose-dependent manner alleviated neuropathic pain-related behaviors in rats after sciatic nerve injury. Cenicriviroc decreased the activation and/or infiltration of IBA-1-positive cells (microglia/macrophages) in the spinal cord and DRG, and satellite cells in the DRG, and likely as a consequence reduced the level of some important pronociceptive factors (IL-1beta, IL-6, IL-18, and CCL3). Importantly, from a clinical perspective, cenicriviroc enhanced the analgesic potency of morphine and buprenorphine. These beneficial behavioral effects may result, among others, from the influence of cenicriviroc on the mRNA level of opioid receptors (MOR, DOR, KOR, and NOR) at the DRG level. Our results provide the first evidence that simultaneous targeting of CCR2 and CCR5 using cenicriviroc may have great potential for use in neuropathic pain therapies, especially since it is already under clinical trials, though in other health concerns[3].
References:
[1]. Lefebvre E, Moyle G, et al. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis. PLoS One. 2016 Jun 27;11(6):e0158156.
[2].Okamoto M, Toyama M, et al. The chemokine receptor antagonist cenicriviroc inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Oct;182:104902.
[3].Kwiatkowski K, Pawlik K, et al. Bidirectional Action of Cenicriviroc, a CCR2/CCR5 Antagonist, Results in Alleviation of Pain-Related Behaviors and Potentiation of Opioid Analgesia in Rats With Peripheral Neuropathy. Front Immunol. 2020 Dec 21;11:615327.
Cenicriviroc (CVC) 是一种口服的 CCR2/CCR5 双重拮抗剂，对这两种受体具有纳摩尔效力[1]。
Cenicriviroc 是一种小分子趋化因子受体拮抗剂，通过拮抗作为 HIV-1 辅助受体的 CCR5，具有高效和选择性的抗人类免疫缺陷病毒 1 型 (HIV-1) 活性。 Cenicriviroc 还强烈拮抗 CCR2b，因此具有有效的抗炎和免疫调节作用[2]。
Cenicriviroc 是 SARS-CoV-2 复制的选择性抑制剂。当 VeroE6/TMPRSS2 细胞感染 SARS-CoV-2 并在没有化合物的情况下孵育 3 天时，细胞被病毒诱导的完全破坏细胞病变效应（图 1 B）。在 20 μM Cenicriviroc 存在的情况下，没有观察到受感染细胞的这种细胞破坏，尽管发现了一些形态学变化[3]。
以剂量依赖性方式重复鞘内注射 Cenicriviroc 可减轻坐骨神经损伤后大鼠的神经性疼痛相关行为。 Cenicriviroc 降低了脊髓和 DRG 中 IBA-1 阳性细胞（小胶质细胞/巨噬细胞）以及 DRG 中卫星细胞的激活和/或浸润，并可能因此降低了一些重要的伤害感受因子（IL- 1beta、IL-6、IL-18 和 CCL3）。重要的是，从临床角度来看，cenicriviroc 增强了吗啡和丁丙诺啡的镇痛效力。除其他外，这些有益的行为影响可能是由于 cenicriviroc 对 DRG 水平的阿片受体（MOR、DOR、KOR 和 NOR）mRNA 水平的影响。我们的结果提供了第一个证据，表明使用 cenicriviroc 同时靶向 CCR2 和 CCR5 可能具有用于神经性疼痛治疗的巨大潜力，特别是因为它已经在进行临床试验，尽管在其他健康问题上[3] .