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 PROTEIN) of this virus enables binding to the human receptor
ACE2 HGNC, and hence presents a prime target for vaccines preventing viral entry into host cells1. The
S proteins PROTEIN from
SARS-CoV-1 and SARS-CoV-2 MESHD are similar2, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-CoV-1-specific neutralizing antibodies to inhibit SARS-CoV-23. Here we used comparative pangenomic analysis of all sequenced Betacoronaviruses to reveal that, among all core gene clusters present in these viruses, the
envelope protein E PROTEIN shows a variant shared by SARS and SARS-Cov2 with two completely-conserved key functional features, an ion-channel and a PDZ-binding Motif (PBM). These features trigger a cytokine storm that activates the inflammasome, leading to increased
edema MESHD in lungs causing the
acute respiratory distress syndrome MESHD (
ARDS MESHD)4-6, the leading cause of
death MESHD in
SARS-CoV-1 and SARS-CoV-2 infection7 MESHD SARS-CoV-2 infection MESHD7,8. However, three drugs approved for human use may inhibit SARS-CoV-1 and SARS-CoV-2
Protein E PROTEIN, either acting upon the ion channel (Amantadine and Hexamethylene amiloride9,10) or the PBM (SB2035805), thereby potentially increasing the survival of the host, as already demonstrated for SARS-CoV-1in animal models. Hence, blocking the SARS
protein E PROTEIN inhibits development of ARDS in vivo. Given that our results demonstrate that the
protein E PROTEIN subcluster for the SARS clade is quasi-identical for the key functional regions of SARS-CoV-1 and SARS-CoV-2, we conclude that use of approved drugs shown to act as SARS
E protein PROTEIN inhibitors can help prevent further casualties from COVID-2019 while vaccines and other preventive measures are being developed.