局部应用的天门冬氨酸钠，一种无毒的多阴离子树状聚合物，在实验性眼部腺病毒感染模型中显示出抗病毒活性。
Topical Astodrimer Sodium, a Non-Toxic Polyanionic Dendrimer, Demonstrates Antiviral Activity in an Experimental Ocular Adenovirus Infection Model.
机构信息
The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Starpharma Pty Ltd., 4-6 Southampton Crescent, Abbotsford, VIC 3067, Australia.
出版信息
Molecules. 2021 Jun 5;26(11):3419. doi: 10.3390/molecules26113419.
There is no approved antiviral therapy for adenovirus (HAdV) ocular infections. Astodrimer sodium (SPL7013) is a polyanionic dendrimer with antiviral activity. The current study evaluated the ocular tolerability and anti-adenoviral efficacy of topical SPL7013 in rabbit ocular models. In a tolerability study, rabbits were treated with 3% SPL7013, vehicle, or 0.5% cidofovir. Their eyes were graded using the Draize scale. In antiviral efficacy studies, HAdV5 inoculated eyes were treated with 3% SPL7013, vehicle, or 0.5% cidofovir. Eyes were cultured for the virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Viral titers were determined. There were no differences in Draize scores between 3% SPL7013 and vehicle on any day. Cidofovir produced significantly higher Draize scores on day 12 than SPL7013 and vehicle. The 3% SPL7013 and 0.5% cidofovir significantly reduced daily viral titers and positive cultures per total compared with vehicle on several different days. The 3% SPL7013 and 0.5% cidofovir significantly reduced the duration of HAdV5 shedding compared to vehicle. The 3% SPL7013 demonstrated significantly more antiviral activity compared with vehicle in the Ad5/NZW rabbit ocular model. The 3% SPL7013 induced "minimal" to "practically non-irritating" Draize scores in the ocular tolerability study. Further development of astodrimer sodium as a topical antiviral therapy for adenoviral ocular infections is indicated.
目前尚无针对腺病毒（HAdV）眼部感染的批准抗病毒疗法。阿地溴铵钠（SPL7013）是一种具有抗病毒活性的多阴离子树突。本研究评估了局部 SPL7013 在兔眼模型中的眼部耐受性和抗腺病毒功效。在耐受性研究中，用 3% SPL7013、载体或 0.5%更昔洛韦对兔子进行治疗。用 Draize 量表对其眼部进行评分。在抗病毒功效研究中，用 3% SPL7013、载体或 0.5%更昔洛韦对接种 HAdV5 的眼睛进行治疗。在第 0、1、3、4、5、7、9、11 和 14 天对眼睛进行病毒培养。测定病毒滴度。在任何一天，3% SPL7013 与载体之间的 Draize 评分均无差异。与 SPL7013 和载体相比，更昔洛韦在第 12 天引起的 Draize 评分明显更高。与载体相比，3% SPL7013 和 0.5%更昔洛韦在不同天数可显著降低每日病毒滴度和总阳性培养数。与载体相比，3% SPL7013 和 0.5%更昔洛韦可显著缩短 HAdV5 脱落时间。与载体相比，3% SPL7013 在 Ad5/NZW 兔眼模型中表现出更强的抗病毒活性。在眼部耐受性研究中，3% SPL7013 诱导的 Draize 评分“最小”至“实际上无刺激性”。表明阿地溴铵钠作为治疗腺病毒眼部感染的局部抗病毒疗法具有进一步开发的潜力。
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