Structural analysis of SARS-CoV-2 genome and predictions of the human interactome
Vandelli, Andrea (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Monti, Michele (Universitat Pompeu Fabra)
Milanetti, Edoardo (Sapienza Università di Roma)
Armaos, Alexandros (Universitat Pompeu Fabra)
Rupert, Jakob (Istituto Italiano di Tecnologia)
Zacco, Elsa (Istituto Italiano di Tecnologia)
Bechara, Elias (Universitat Pompeu Fabra)
Delli Ponti, Riccardo (Nanyang Technological University)
Tartaglia, Gian Gaetano (Universitat Pompeu Fabra)

Data:	2020
Resum:	Specific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of >2000 coronaviruses and computed >100 000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genomic regions display different degrees of conservation. SARS-CoV-2 domain encompassing nucleotides 22 500-23 000 is conserved both at the sequence and structural level. The regions upstream and downstream, however, vary significantly. This part of the viral sequence codes for the Spike S protein that interacts with the human receptor angiotensin-converting enzyme 2 (ACE2). Thus, variability of Spike S is connected to different levels of viral entry in human cells within the population. Our predictions indicate that the 5' end of SARS-CoV-2 is highly structured and interacts with several human proteins. The binding proteins are involved in viral RNA processing, include double-stranded RNA specific editases and ATP-dependent RNA-helicases and have strong propensity to form stress granules and phase-separated assemblies. We propose that these proteins, also implicated in viral infections such as HIV, are selectively recruited by SARS-CoV-2 genome to alter transcriptional and post-transcriptional regulation of host cells and to promote viral replication.
Ajuts:	European Commission 309545 European Commission 855923 European Commission 727658 European Commission 825070 Agencia Estatal de Investigación BFU2017-86970-P
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Nucleic acids research, Vol. 48, Issue 20 (November 2020) , p. 11270-11283, ISSN 1362-4962

DOI: 10.1093/nar/gkaa864
PMID: 33068416

14 p, 2.4 MB

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