Functional Pangenome Analysis Shows Key Features of E Protein Are Preserved in SARS and SARS-CoV-2

Intikhab Alam, Allan A. Kamau, Maxat Kulmanov, Łukasz Jaremko, Stefan T. Arold, Arnab Pain, Takashi Gojobori, Carlos M. Duarte
2020 Frontiers in Cellular and Infection Microbiology  
The spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social, and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells. The S proteins from SARS and SARS-CoV-2 are similar, but structural differences in the receptor binding domain (RBD) preclude the use
more » ... of SARS-specific neutralizing antibodies to inhibit SARS-CoV-2. Here we used comparative pangenomic analysis of all sequenced reference Betacoronaviruses, complemented with functional and structural analyses. This analysis reveals that, among all core gene clusters present in these viruses, the envelope protein E shows a variant cluster shared by SARS and SARS-CoV-2 with two completely-conserved key functional features, namely an ion-channel, and a PDZ-binding motif (PBM). These features play a key role in the activation of the inflammasome causing the acute respiratory distress syndrome, the leading cause of death in SARS and SARS-CoV-2 infections. Together with functional pangenomic analysis, mutation tracking, and previous evidence, on E protein as a determinant of pathogenicity in SARS, we suggest E protein as an alternative therapeutic target to be considered for further studies to reduce complications of SARS-CoV-2 infections in COVID-19.
doi:10.3389/fcimb.2020.00405 pmid:32850499 pmcid:PMC7396417 fatcat:seowgiqpxnfkzfia6szqmnewte