Compostos doadores de óxido-nítrico como potenciais inibidores do SARS-CoV-2. (Revisão Bibliográfica)
Data
2022-06-24
Autores
Gaspar, Ana Beatriz [UNIFESP]
Orientadores
Reis, Adriana Karla Cardoso Amorim [UNIFESP]
Tipo
Trabalho de conclusão de curso de graduação
Título da Revista
ISSN da Revista
Título de Volume
Resumo
As proteases de vírus são alvos interessantes para o tratamento de doenças, como do HIV e Hepatite C. A protease principal do vírus SARS-CoV-2 possui um resíduo de cisteína, que pode S-nitrosilada na presença de óxido nítrico (NO), a modificação do grupo tiol (SH) leva a inativação da protease, que é responsável pelo processamento das poliproteínas que estão envolvidas na replicação viral. Compostos doadores de NO possuem a habilidade de liberal o radical, in vivo, para que a reação de S-nitrosilação ocorra. Alguns doadores já são conhecidos, como nitratos orgânicos e NONOatos. Uma nova classe que está ganhando visibilidade são os S-nitrosotiois, que possuem potencial para agirem como inibidores de cisteíno-proteases. Em 2020, foi declarada pela Organização Mundial da Saúde (OMS) a pandemia global de COVID-19. Essa doença é causada pelo vírus SARS-CoV-2, uma nova espécie de coronavírus. As proteases virais do novo coronavírus possuem resíduos de cisteína livres que são essenciais na replicação do RNA do genoma viral no organismo, após a reação de S-nitrosilação essa ação fica comprometida. O NO também tem a capacidade de diminuir a superprodução de interleucinas, TNF-α (Fator de necrose tumoral alfa) e dímeros-D.
Virus proteases are interesting targets for the treatment of diseases such as HIV and Hepatitis C. The main protease of the SARS-CoV-2 virus has a cysteine residue, which can be S-nitrosylated in the presence of nitric oxide (NO), modification of the thiol group (SH) leads to inactivation of the protease, which is responsible for processing the polyproteins that are involved in viral replication. NO donor compounds have the ability to free the radical, in vivo, for the S-nitrosylation reaction to occur. Some donors are already known, such as organic nitrates and NONOates. A new class that is gaining visibility are the S-nitrosothiols, which have the potential to act as inhibitors of cysteine proteases. In 2020, the World Health Organization (WHO) declared the global pandemic of COVID-19. This disease is caused by the SARS-CoV-2 virus, a new species of coronavirus. The viral proteases of the new coronavirus have free cysteine residues that are essential in the replication of the RNA of the viral genome in the body, after the S-nitrosylation reaction this action is compromised. NO also has the ability to decrease the overproduction of interleukins, TNF-α (Tumor Necrosis Factor alpha) and D-dimers.
Virus proteases are interesting targets for the treatment of diseases such as HIV and Hepatitis C. The main protease of the SARS-CoV-2 virus has a cysteine residue, which can be S-nitrosylated in the presence of nitric oxide (NO), modification of the thiol group (SH) leads to inactivation of the protease, which is responsible for processing the polyproteins that are involved in viral replication. NO donor compounds have the ability to free the radical, in vivo, for the S-nitrosylation reaction to occur. Some donors are already known, such as organic nitrates and NONOates. A new class that is gaining visibility are the S-nitrosothiols, which have the potential to act as inhibitors of cysteine proteases. In 2020, the World Health Organization (WHO) declared the global pandemic of COVID-19. This disease is caused by the SARS-CoV-2 virus, a new species of coronavirus. The viral proteases of the new coronavirus have free cysteine residues that are essential in the replication of the RNA of the viral genome in the body, after the S-nitrosylation reaction this action is compromised. NO also has the ability to decrease the overproduction of interleukins, TNF-α (Tumor Necrosis Factor alpha) and D-dimers.