Shanghai Institute of Biological Products Co., Ltd., Shanghai 201403, China.
Division of Hepatitis and Enterovirus Vaccines, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Institute of Biological Products, National Institutes for Food and Drug Control, Beijing 102600, China.
Viruses. 2022 Nov 4;14(11):2451. doi: 10.3390/v14112451.
Small molecular nucleic acid drugs produce antiviral effects by activating pattern recognition receptors (PRRs). In this study, a small molecular nucleotide containing 5'triphosphoric acid (5'PPP) and possessing a double-stranded structure was designed and named nCoV-L. nCoV-L was found to specifically activate RIG-I, induce interferon responses, and inhibit duplication of four RNA viruses (Human enterovirus 71, Human poliovirus 1, Huma coxsackievirus B5 and Influenza A virus) in cells. In vivo, nCoV-L quickly induced interferon responses and protected BALB/c suckling mice from a lethal dose of the enterovirus 71. Additionally, prophylactic administration of nCoV-L was found to reduce mouse death and relieve morbidity symptoms in a K18-hACE2 mouse lethal model of SARS-CoV-2. In summary, these findings indicate that nCoV-L activates RIG-I and quickly induces effective antiviral signals. Thus, it has potential as a broad-spectrum antiviral drug.
小分子核酸药物通过激活模式识别受体（PRRs）产生抗病毒作用。在这项研究中，设计并命名了一种含有 5'三磷酸（5'PPP）和双链结构的小分子核苷酸，命名为 nCoV-L。研究发现 nCoV-L 特异性地激活 RIG-I，诱导干扰素反应，并抑制四种 RNA 病毒（人肠道病毒 71、人脊髓灰质炎病毒 1、人柯萨奇病毒 B5 和流感 A 病毒）在细胞中的复制。在体内，nCoV-L 能迅速诱导干扰素反应，并保护 BALB/c 乳鼠免受肠道病毒 71 的致死剂量感染。此外，预防性给予 nCoV-L 可降低 K18-hACE2 小鼠 SARS-CoV-2 致死模型中病毒载量，减少小鼠死亡并缓解发病症状。综上所述，这些发现表明 nCoV-L 可激活 RIG-I 并迅速诱导有效的抗病毒信号，因此具有成为广谱抗病毒药物的潜力。
