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First Author: Mariana G. Ferrarini & Avantika Lal 

Journal/preprint name: Research Square 

Paper DOI10.21203/rs.3.rs-63136/v1 

Tags: bioinformatics, RNA-seq, pathogenesis, mechanism 

Summary 

Ferrarini et al aimed to characterize the host response triggered specifically by SARS-CoV-2 infection. They addressed this using a publicly available RNA-seq dataset of human lung cells infected with SARS-CoV-2 and other respiratory viruses. Based on identification of SARS-CoV-2 specific geneisoform, and pathway responses, they predicted putative interactions between the viral RNA genome and human RNA-binding proteins (RBP). Four viral sequence variants were identified to potentially play a role in disease severity. The host factors identified could serve as potential novel drug target. 

Research Highlights 

  1.  Analysis of host-pathogen interaction on a cellular level which specifically contribute to SARS-CoV-2 replication and pathogenesis 

  1. Identification of RBP binding sites, which interact with SARS-CoV-2 in a conserved and specific way 

  1. SARS-CoV-2 virus protein translation could be EIF4B-dependent 

  1. Creation of publicly available workflow for mechanistic analysis on emerging pathogens 

Impact for COVID-19 research:  

  • Interaction of SARS-CoV-2 with human cells on a molecular level helps understanding the specific mechanism of pathology, creating novel drug targets/prophylactics 

  • The findings need to be validated in vitro/in vivo as it’s an in silico study 

Methodologies: 

  • Study Typein silico 

  • Important cell lines/viral models used: NHBE, A549, Calu-3, original SARS-CoV-2, influenza A virus, respiratory syncytial virus and human parainfluenza virus 3 (dataset from Blanco-Melo et al., Cell, 2020) 

  • Key Techniques: bioinformatics 

Limitations: 

  • Host interaction analysis based on cell line data not always applicable to in vivo scenarioalso doesn’t differentiate between different severities of COVID-19 

  • As stated in the discussion, there might be a bias regarding collection time of viral genomes in the pandemic