Integrative transcriptome analysis of SARS-CoV-2 human-infected cells combined with deep learning algorithms identifies two potential cellular targets for the treatment of coronavirus disease.

Journal: Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]
Published Date:

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly spread worldwide, leading coronavirus disease 2019 (COVID-19) to hit pandemic level less than 4 months after the first official cases. Hence, the search for drugs and vaccines that could prevent or treat infections by SARS-CoV-2 began, intending to reduce a possible collapse of health systems. After 2 years, efforts to find therapies to treat COVID-19 continue. However, there is still much to be understood about the virus' pathology. Tools such as transcriptomics have been used to understand the impact of SARS-CoV-2 on different cells isolated from various tissues, leaving datasets in the databases that integrate genes and differentially expressed pathways during SARS-CoV-2 infection. After retrieving transcriptome datasets from different human cells infected with SARS-CoV-2 available in the database, we performed an integrative analysis associated with deep learning algorithms to determine differentially expressed targets mainly after infection. The targets found represented a fructose transporter (GLUT5) and a component of proteasome 26s. These targets were then molecularly modeled, followed by molecular docking that identified potential inhibitors for both structures. Once the inhibition of structures that have the expression increased by the virus can represent a strategy for reducing the viral replication by selecting infected cells, associating these bioinformatics tools, therefore, can be helpful in the screening of molecules being tested for new uses, saving financial resources, time, and making a personalized screening for each infectious disease.

Authors

  • Ricardo Lemes Gonçalves
    Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, 35400-000, Brazil.
  • Gabriel Augusto Pires de Souza
    Laboratório de Vacinas, Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700, 37130-001, Alfenas, Brazil.
  • Mateus de Souza Terceti
    Laboratório de Vacinas, Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700, 37130-001, Alfenas, Brazil.
  • Renato Fróes Goulart de Castro
    Laboratório de Vacinas, Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700, 37130-001, Alfenas, Brazil.
  • Breno de Mello Silva
    Núcleo de Pesquisas em Ciências Biológicas, NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, 35400-000, Brazil.
  • Romulo Dias Novaes
    Instituto de Ciências Biomédicas, Departamento de Biologia Estrutural, Universidade Federal de Alfenas, Alfenas, Minas Gerais, Brazil.
  • Luiz Cosme Cotta Malaquias
    Laboratório de Vacinas, Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700, 37130-001, Alfenas, Brazil.
  • Luiz Felipe Leomil Coelho
    Laboratório de Vacinas, Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700, 37130-001, Alfenas, Brazil. luiz.coelho@unifal-mg.edu.br.