Compostos de coordenação como uma abordagem inovadora contra vírus dos gêneros alfavírus e betacoronavírus

• Autor(a) principal: Santos, Igor Andrade
• Data de Publicação: 2023
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFU
• Texto Completo: https://repositorio.ufu.br/handle/123456789/39555; http://doi.org/10.14393/ufu.te.2023.616
• topic: Antivirais; CHIKV; SARS-CoV-2; Complexos metálicos; CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA::BIOLOGIA E FISIOLOGIA DOS MICROORGANISMOS::VIROLOGIA; Imunologia; ODS::ODS 3. Saúde e bem-estar - Assegurar uma vida saudável e promover o bem-estar para todos, em todas as idades.; ODS::ODS 9. Indústria, Inovação e infraestrutura - Construir infraestrutura resiliente, promover a industrialização inclusiva e sustentável, e fomentar a inovação.

Diseases caused by emerging viruses represent important causes of outbreaks and epidemics, impacting individuals' lives, healthcare services, and the economy. For example, the COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has heightened the demand for antivirals and challenged the world in controlling viral spread. Brazil also faces a critical scenario related to the control of arboviruses, such as infections caused by the chikungunya virus (CHIKV), the agent responsible for chikungunya fever. Currently, there is no antiviral therapy against CHIKV, and only three drugs licensed for severe cases of COVID-19, making the development of antiviral drugs against these viruses essential and urgent. In this context, metal complexes have drawn attention due to their efficacy and versatility, as metal ions such as gold (Au), platinum (Pt), palladium (Pd), and copper (Cu), when complexed with specific ligands, can generate stable, biologically active, and non-cytotoxic compounds. Therefore, we evaluated a series of coordination compounds formed by the association of Au(II), Pt(II), Pd(II), and Cu(I) ions with organic molecules, such as the aminoadamantanes memantine (mtn), rimantadine (rtd), and amantadine (atd), heterocyclic carbenes, and/or chalcones, against SARS-CoV-2 and CHIKV. The coordinated compounds showed selectivity indices (SI) between 1.7 and 36.2, and different inhibition profiles, interfering with viral replication through different modes of action, either by inhibiting virus entry into host cells, interacting with dsRNA in both viruses and interrupting viral replication, and/or reducing cell-to-cell spread of SARS-CoV-2. Hence, the work described here allowed for the identification of antivirals that inhibit viruses from different families, potentially being capitalized in the treatment of COVID-19 and Chikungunya Fever. Therefore, the results presented here may contribute to the development of new antiviral drugs, thereby improving the population's quality of life. Additionally, we hope that the results of this work will stimulate further studies with metal coordination compounds and the development of new, unprecedented molecules with the potential to be applied not only for current diseases but also for future outbreaks, endemics, and epidemics.