Ceña-Diez Rafael, García-Broncano Pilar, de la Mata Francisco Javier, Gómez Rafael, Muñoz-Fernández M Ángeles
Hospital General Universitario Gregorio Marañon, Majadahonda, Spain; Instituto de Investigación Sanitaria Gregorio Marañon, Majadahonda, Spain; Spanish HIV HGM Biobank, Majadahonda, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Majadahonda, Spain.
Hospital General Universitario Gregorio Marañon, Majadahonda, Spain; Instituto de Investigación Sanitaria Gregorio Marañon, Majadahonda, Spain; Spanish HIV HGM Biobank, Majadahonda, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Majadahonda, Spain; Laboratory of Viral Infection and Immunity, National Center of Microbiology, Health Institute of Carlos III, Majadahonda, Spain.
Int J Nanomedicine. 2016 May 30;11:2443-50. doi: 10.2147/IJN.S104292. eCollection 2016.
The development of a safe and effective microbicide to prevent the sexual transmission of human immunodeficiency virus (HIV)-1 is urgently needed. Unfortunately, the majority of microbicides, such as poly(L-lysine)-dendrimers, anionic polymers, or antiretrovirals, have proved inactive or even increased the risk of HIV infection in clinical trials, most probably due to the fact that these compounds failed to prevent semen-exposed HIV infection. We showed that G2-S16 dendrimer exerts anti-HIV-1 activity at an early stage of viral replication, blocking the gp120/CD4/CCR5 interaction and providing a barrier to infection for long periods, confirming its multifactorial and nonspecific ability. Previously, we demonstrated that topical administration of G2-S16 prevents HIV transmission in humanized BLT mice without irritation or vaginal lesions. Here, we demonstrated that G2-S16 is active against mock- and semen-exposed HIV-1 and could be a promising microbicide against HIV infection.
迫切需要开发一种安全有效的杀微生物剂来预防人类免疫缺陷病毒1型（HIV-1）的性传播。不幸的是，大多数杀微生物剂，如聚（L-赖氨酸）树枝状聚合物、阴离子聚合物或抗逆转录病毒药物，在临床试验中已被证明无活性，甚至增加了HIV感染的风险，这很可能是因为这些化合物未能预防精液暴露的HIV感染。我们发现G2-S16树枝状聚合物在病毒复制的早期阶段发挥抗HIV-1活性，阻断gp120/CD4/CCR5相互作用，并长期为感染提供屏障，证实了其多因素和非特异性能力。此前，我们证明局部施用G2-S16可预防人源化BLT小鼠中的HIV传播，且无刺激或阴道损伤。在此，我们证明G2-S16对模拟暴露和精液暴露的HIV-1具有活性，可能是一种有前景的抗HIV感染杀微生物剂。
