New therapeutic approaches of nanoparticles against infectionsHIV-1, HSV-1 and RSV

Resumen

Biological fields related to virology and viral infections have been put under the spotlight during the last two years on account of SARS-CoV-2 global pandemic. However, viral infections have been a major health problem from the beginning of mankind. Landing this question, only the three viral pathogens related to this doctoral thesis, the human immunodeficiency virus type 1 (HIV-1), the herpes simplex virus type 1 (HSV-1) and the respiratory syncytial virus (RSV) are responsible of approximately 10-15 million of new infection annually, and directly related with around 2 million deaths every year. The lack of an effective approv􀂎􀂍 vaccine against those viral pathogens, together with fact that no effective antiviral treatments are implemented against HSV-1, once invading central nervous system, and RSV, besides treatment resistance mutation appearance in HIV-1 treatments exhort scientific community developing new therapeutic approaches and therapeutic strategies to face this situation. Herein, a series of new nanoparticles have been described against HIV-1, HSV-1 and RSV infections with promising results. G2-S16 dendrimer demonstrated to efficiently inhibit HIV-1 infection and not generating resistance mutations appearance leading to continued treatment. Furthermore, G2-S16 demonstrated to inhibit dendrimer-resistant viruses, placing this dendrimer as candidate for treatment failure or resistant individuals, improving antiretroviral current treatments. Additionally, due to inhibitory G2-S16 mechanism, this dendrimer also demonstrated to halt RSV infection intranasally administrated in mice model, demonstrating their underlaying mechanism of action. PEGylated cationic dendrimers here described as new microRNAs delivery system demonstrated releasing constitutive anti-HIV miRNAs into the host cells, inducing gene silencing for HIV-1 protein synthesis, impeding generation of new functional virions. Finally, new family of crossing blood brain barrier gold nanoparticles demonstrated to efficiently inhibit HSV-1 central nervous system invading infection been biocompatible once intravenously injected.