Introduction
The SARS-CoV-2 virus infects human cells by first binding via its S protein to its receptor: Angiotensin Converting Enzyme 2 (ACE2), a 120 kDa integral membrane glycoprotein on the surface of cells in the lungs, heart, kidneys, and intestine (Wan et al., 2020; Zhang et al., 2020; Zhou et al., 2020a; Hamming et al., 2004). Binding of SARS coronaviruses to ACE2 is followed by fusion of the viral and plasma membranes, endocytosis and cellular infection of the virus (Inoue at al., 2007; He et al., 2020). ACE2 expression in respiratory epithelium is important in the pathobiology of COVID-19 (Xu et al., 2020a). The infection typically begins in epithelia in the upper respiratory tract, before spreading to alveoli in the lungs (Xu et al., 2020a; Zhou et al., 2020a), pathologic events that are more severe in patients with compromised immune response or ability to combat the spread of infection (Rothan & Byrareddy, 2020). COVID-19 typically (in 80% of patients) causes mild symptoms, Wu & McGoogan, 2020) but severe morbidity in a subset of patients, requiring hospitalization, intensive care and in some cases, death. Increased morbidity and mortality occur in patients with comorbidities, especially ones associated with aging, including hypertension, cardiac disease, diabetes, chronic lung disease, and compromised immunity (Zhou et al., 2020a; Wu & McGoogan, 2020). Many strategies, are being pursued in response to the urgent need for effective therapies of COVID-19 (e.g., Stebbing et al., 2020; Gautret et al., 2020).
The SARS-CoV-2 virus shares many characteristics with the SARS-CoV-1 coronavirus, which caused a pandemic in 2002-2003 (He et al., 2020; Wan et al., 2020). Common features include ~80% shared sequence identity in their viral genomes (He et al., 2020), the range of tissues that are infected, mortality from acute respiratory distress syndrome (ARDS) and their cellular receptor: ACE2 (Wan et al., 2020; Zhang et al., 2020; Zhou et al., 2020a; Zhou et al., 2020b). Compared to SAR-COV-1, SARS-CoV-2 has ~4-fold higher affinity for ACE2 (Walls et al., 2020). Due to their similarities, information related to SARS-CoV-1 can aid in development of hypotheses for treatment of SARS-CoV2, including the repurposing of pharmacological agents approved for use in humans.