RESUMEN
Coronavirus disease 19 (COVID-19) continues to challenge most scientists in the search of an effective way to either prevent infection or to avoid spreading of the disease. As result of global efforts some advances have been reached and we are more prepared today than we were at the beginning of the pandemic, however not enough to stop the transmission, and many questions remain unanswered. The possibility of reinfection of recovered individuals, the duration of the immunity, the impact of SARS-CoV-2 mutations in the spreading of the disease as well as the degree of protection that a potential vaccine could have are some of the issues under debate. A number of vaccines are under development using different platforms and clinical trials are ongoing in different countries, but even if they are licensed it will need time until reach a definite conclusion about their real safety and efficacy. Herein we discuss the different strategies used in the development of COVID-19 vaccines, the questions underlying the type of immune response they may elicit, the consequences that new mutations may have in the generation of sub-strains of SARS-CoV-2 and their impact and challenges for the efficacy of potential vaccines in a scenario postpandemic.
Asunto(s)
Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Inmunidad Humoral/genética , SARS-CoV-2/genética , COVID-19/virología , Variación Genética , HumanosRESUMEN
Despite intense research there is currently no effective vaccine available against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in the later 2019 and responsible for the COVID-19 pandemic. This infectious and communicable disease has become one of the major public health challenges in the world. The clinical management of COVID-19 has been limited to infection prevention and control measures associated with supportive care such as supplemental oxygen and mechanical ventilation. Meanwhile efforts to find an effective treatment to inhibit virus replication, mitigate the symptoms, increase survival and decrease mortality rate are ongoing. Several classes of drugs, many of them already in use for other diseases, are being evaluated based on the body of clinical knowledge obtained from infected patients regarding to the natural history and evolution of the infection. Herein we will provide an updated overview of the natural history and current knowledge on drugs and therapeutic agents being tested for the prevention and treatment of COVID-19. These include different classes of drugs such as antiviral agents (chloroquine, ivermectin, nitazoxanide, hydroxychloroquine, lopinavir, remdesivir, tocilizumab), supporting agents (Vitamin C, Vitamin D, azithromycin, corticosteroids) and promising investigational vaccines. Considering the controversies and excessive number of compounds being tested and reported in the literature we hope that this review can provide useful and updated consolidated information on potential drugs used to prevent, control and treat COVID-19 patients worldwide.
Asunto(s)
Antivirales/farmacología , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Animales , Betacoronavirus/efectos de los fármacos , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Diseño de Fármacos , Humanos , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/virología , Salud Pública , SARS-CoV-2 , Vacunas Virales/administración & dosificación , Tratamiento Farmacológico de COVID-19RESUMEN
Novel metal complexes have received great attention in the last decades due to their potential anticancer activity. Notably, ruthenium-based complexes have emerged as good alternative to the currently used platinum-based drugs for cancer therapy, providing less toxicity and side effects to patients. Glioblastoma is an aggressive and invasive type of brain tumor and despite of advances is the field of neurooncology there is no effective treatment until now. Therefore, we sought to investigate the potential antiproliferative activity of phosphine-ruthenium-based complexes on human glioblastoma cell lines. Due to its octahedral structure as opposed to the square-planar geometry of platinum(II) compounds, ruthenium(II) complexes exhibit different structure-function relationship probably acting through a different mechanism from that of cisplatin beyond their ability to bind DNA. To better improve the pharmacological activity of metal complexes we hypothesized that neutron activation of ruthenium in the complexes would allow to decrease the effective concentration of the compound needed to kill tumor cells. Herein we report on the effect of unmodified and neutron activated phosphine ruthenium II complexes on glioblastoma cell lines carrying wild-type and mutated p53 tumor suppressor gene. Induction of apoptosis/authophagy as well as generation of reactive oxygen species were determined. The phosphine ruthenium II complexes tested were highly active against glioblastoma cell lines inducing cell death both through apoptosis and autophagy in a p53 independent fashion. Neutron activation of ruthenium compounds rendered them more active than their original counterparts suggesting a new strategy to improve the antitumor activity of these compounds.