Este artigo é um Preprint
Preprints são relatos preliminares de pesquisa que não foram certificados pela revisão por pares. Eles não devem ser considerados para orientar a prática clínica ou comportamentos relacionados à saúde e não devem ser publicados na mídia como informação estabelecida.
Preprints publicados online permitem que os autores recebam feedback rápido, e toda a comunidade científica pode avaliar o trabalho independentemente e responder adequadamente. Estes comentários são publicados juntamente com os preprints para qualquer pessoa ler e servir como uma avaliação pós-publicação.
SARS-CoV-2 3CLpro Whole Human Proteome Cleavage Prediction and Enrichment/Depletion Analysis (preprint)
biorxiv; 2020.
Preprint
em Inglês
| bioRxiv | ID: ppzbmed-10.1101.2020.08.24.265645
ABSTRACT
A novel coronavirus (SARS-CoV-2) has devastated the globe as a pandemic that has killed more than 800,000 people. Effective and widespread vaccination is still uncertain, so many scientific efforts have been directed towards discovering antiviral treatments. Many drugs are being investigated to inhibit the coronavirus main protease, 3CLpro, from cleaving its viral polyprotein, but few publications have addressed this proteases interactions with the host proteome or their probable contribution to virulence. Too few host protein cleavages have been experimentally verified to fully understand 3CLpros global effects on relevant cellular pathways and tissues. Here, we set out to determine this proteases targets and corresponding potential drug targets. Using a neural network trained on coronavirus proteomes with a Matthews correlation coefficient of 0.983, we predict that a large proportion of the human proteome is vulnerable to 3CLpro, with 4,460 out of approximately 20,000 human proteins containing at least one predicted cleavage site. These cleavages are nonrandomly distributed and are enriched in the epithelium along the respiratory tract, brain, testis, plasma, and immune tissues and depleted in olfactory and gustatory receptors despite the prevalence of anosmia and ageusia in COVID-19 patients. Affected cellular pathways include cytoskeleton/motor/cell adhesion proteins, nuclear condensation and other epigenetics, host transcription and RNAi, coagulation, pattern recognition receptors, growth factor, lipoproteins, redox, ubiquitination, and apoptosis. This whole proteome cleavage prediction demonstrates the importance of 3CLpro in expected and nontrivial pathways affecting virulence, lead us to propose more than a dozen potential therapeutic targets against coronaviruses, and should therefore be applied to all viral proteases and experimentally verified.
Texto completo:
Disponível
Coleções:
Preprints
Base de dados:
bioRxiv
Assunto principal:
COVID-19
/
Transtornos do Olfato
Idioma:
Inglês
Ano de publicação:
2020
Tipo de documento:
Preprint
Similares
MEDLINE
...
LILACS
LIS