Pesquisadores da UBC identificaram três compostos que previnem a infecção por COVID-19 em células humanas, derivados de fontes naturais, incluindo uma esponja do mar BC.
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)
Inibição sinérgica da infecção por SARS-CoV-2 Omicron (BA.2) pelo uso combinado de bafilomicina D e N-0385. Curvas de dose-resposta de inibição de tratamento único e combinado de bafilomicina D e N-0385 em células Calu-3 infectadas com SARS-CoV-2 foram usadas para a análise usando o aplicativo web de código aberto SynergyFinder. A) Matriz dose-resposta (inibição percentual) da infecção por SARS-CoV-2 com tratamento combinado de bafilomicina D e N-0385. B) Distribuição de sinergia da combinação de pares de bafilomicina D e N-0385 calculada com base no modelo aditivo de Loewe usando SynergyFinder. C)Visualização de paisagem entre bafilomicina D e N-0385 calculada com base no modelo aditivo de Loewe usando SynergyFinder. A superfície é codificada por cores, vermelho indica interações sinérgicas e verde indica interações antagônicas. Crédito: Pesquisa antiviral (2022). DOI: 10.1016/j.antiviral.2022.105484
Pesquisadores da UBC identificaram três compostos que previnem a infecção por COVID-19 em células humanas, derivados de fontes naturais, incluindo uma esponja do mar BC.
A descoberta abre caminho para o desenvolvimento de novos medicamentos para variantes do COVID-19 feitos de fontes naturais. E dada a abundância da natureza, pode haver uma grande quantidade de novos antivirais esperando para serem descobertos.
Em um estudo recente, uma equipe internacional de pesquisadores liderada por cientistas da UBC investigou um catálogo de mais de 350 compostos derivados de fontes naturais, incluindo plantas, fungos e esponjas marinhas, em uma tentativa de encontrar novos medicamentos antivirais que possam ser usados ??para tratar a COVID-19. 19 variantes, como omicron.
"Esta equipe de pesquisa interdisciplinar está desvendando as importantes possibilidades da biodiversidade e dos recursos naturais e descobrindo soluções baseadas na natureza para desafios globais de saúde, como o COVID-19", disse o autor sênior Dr. François Jean, professor associado do departamento de microbiologia e imunologia.
Ao banhar células pulmonares humanas em soluções feitas com esses compostos e, em seguida, infectar as células com SARS-CoV-2, os pesquisadores encontraram 26 compostos que reduziram completamente a infecção viral nas células. Três foram eficazes em doses muito pequenas.
"A vantagem desses compostos é que eles visam as células, e não o vírus, impedindo a replicação do vírus e ajudando a célula a se recuperar", disse a coautora Dra. Jimena Pérez-Vargas, pesquisadora associada do departamento de microbiologia e imunologia. “As células humanas evoluem mais lentamente que os vírus, então esses compostos podem funcionar contra variantes futuras e outros vírus, como o influenza, se usarem os mesmos mecanismos”.
Os pesquisadores usaram uma versão do vírus SARS-CoV-2 que faz com que as células brilhem em verde fluorescente quando infectadas, bem como uma técnica de triagem especial, para identificar os 26 principais compostos naturais que mostraram inibição da infecção por COVID-19 com baixo dano celular . O vírus fluorescente é uma ferramenta poderosa, disse o coautor Dr. Tirosh Shapira, um pós-doutorado na faculdade de medicina.
"Com ele, etapas experimentalmente trabalhosas são redundantes para que possamos verificar fácil e rapidamente milhares de compostos. Ainda mais importante, com ele temos a opção de rastrear o SARS-CoV-2 'ao vivo' à medida que se propaga de uma célula para outra. "
Compostos canadenses
Todos os três compostos mais eficazes foram encontrados no Canadá: alotaketal C de uma esponja marinha coletada em Howe Sound, BC, bafilomicina D de uma bactéria marinha coletada em Barkley Sound, BC, e holyrine A de bactérias marinhas coletadas em águas de Newfoundland.
"Estamos coletando coisas há 40 anos em todo o mundo, mas esses três são canadenses e dois são de BC", disse o coautor Dr. Raymond Andersen, professor do departamento de química.
Testes adicionais mostraram que os três compostos foram eficazes contra a variante delta e várias variantes de ômicron, e são tão seguros para células humanas quanto os tratamentos atuais para COVID-19. Muitos desses tratamentos não são mais eficazes contra as variantes ômicron atualmente circulantes porque o vírus está evoluindo. Isso destaca a necessidade de novos antivirais, disse o Dr. Jean.
Trabalhando em conjunto com outros antivirais
Os pesquisadores exploraram a eficácia do composto bafilomicina D quando usado em combinação com um antiviral COVID-19 descoberto recentemente, a molécula N-0385. Eles descobriram que o composto e a molécula trabalhavam sinergicamente contra a subvariante BA.2 do ômicron. Isso sugere um ponto de partida promissor para o desenvolvimento de tratamentos com múltiplas drogas de variantes de ômicron que são eficazes no tratamento de COVID-19 e outros vírus, disse o Dr. Jean.
Os pesquisadores planejam testar os compostos em modelos animais nos próximos seis meses. "Nossa pesquisa também está abrindo caminho para testes em larga escala de medicamentos de produtos naturais que podem bloquear infecções associadas a outros vírus respiratórios de grande preocupação no Canadá e em todo o mundo, como influenza A e RSV", disse o Dr. Jean.
O artigo foi publicado na revista Antiviral Research .
Mais informações: Jimena Pérez-Vargas et al, Descoberta de produtos naturais líderes para o desenvolvimento de terapêutica pan-SARS-CoV-2, Pesquisa antiviral (2022). DOI: 10.1016/j.antiviral.2022.105484