# Bayesian Model Infers Drug Repurposing Candidates for Treatment of COVID-19
## 4 Discussion
Interestingly, the expression of ACE2 is found in multiple organs including lungs, kidneys and heart, and is associated with incidence and severity of complications such as acute respiratory distress syndrome (ARDS), acute cardiac injuries and kidney injuries [24; 25; 26; 27]. In addition, the viral titer was also predicted as possibly inhibiting carboxopeptidase (CPD), that belongs to a class of enzymes that includes ACE and ACE2, supporting the robustness of the network model. Analysis of the ensemble network to identify enriched drug signatures ranked mTOR as a potential target with the ability to influence the viral titer. This is consistent with clinical reports suggesting Azithromycin, an mTOR inhibitor, as a therapeutic for SARS-CoV-2 infections [28]. In fact, the use of mTOR inhibitors to manage viral infections has been extensively investigated as well as their influence on immune systems, forming the basis for a potential use in SARS-CoV-2 infections [29; 30]. Additionally, enriched drug signature(s) also indicated an association of COVID-19 and the renin-angiotensin system e.g., cyclopenthiazid, a thiazide diuretic that inhibits angiotensin converting enzyme (ACE). Further, a direct linkage of ACE2 to COX6A1 (a member of the mitochondrial Cytochrome C Oxidase complex associated with electron transport and critically engaged with oxidative phosphorylation) and SLC26A3 (electroneutral Cl\({}^{-}\)/HCO\({}_{3}\)+ anti-porter) were identified. Changes in expression of SCL26A3 in the colon has been associated with incidence of infectious diarrhea [31]. Interestingly, in Caco-2 cells (model used in this study), the SLC26A3 transporter activity is regulated by the cystic fibrosis transmembrane conductance regulatory (CFTR) [32]. Given the importance of CFTR and Cl\({}^{-}\)/HCO\({}_{3}\)+ balance in lung physiology [33], the data from the proteomic network provides the basis for a potential lung-regulated acid-base imbalance in SARS-CoV-2 pulmonary manifestations. The viral titer was also inferred as associated with MAOB and CHEK1. The role of MAO as virus receptors has been explored since the 1980's and further supported by literature, demonstrating a relationship between MAO and viral infections [34]. Increases in MAO activity in the brain models of simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) have been reported to be associated with central nervous system disorders [35]. An increase in MAOB mRNA was observed in macaques with severe SIV-associated lesion in the brain and correlated with viral loads [35]. Deprenyl, a MAOB inhibitor, improved verbal memory tests in subjects with mild HIV-associated cognitive impairment compared to patients not taking deprenyl [36]. In addition, given the wide-spread use of MAOB inhibitors (e.g., selegiline, rasagiline, safinamide) in clinical management of Parkinson's Disease (PD) [37], determination of the prevalence of COVID-19 in cohort of PD patients could provide a rapid validation of a role of MOAB in the time-course of COVID-19. Furthermore, such validation would support the use of MOAB inhibitors as supportive therapy in patients with active SARS-CoV-2 infections to improve management and outcomes. Orthogonal support of the potential role of MAO-B in the regulation of SARS-CoV-2 viral titer is the enrichment of these linkages identified within the serntraline drug signatures. Sertaline, a class of Selective Serotonin Reuptake Inhibitors (SSRIs), is used in the treatment of major depressive disorder (MDD), including patients with Parkinson's Disease diagnosed with depression as comorbidity. Although increase in expression of MAO-A in the brain in MDD has been established, the status of MAO-B is unclear. However, inhibitors of MAO enzyme can have the ability to inhibit activity of both enzymes and have known drug interactions with SSRIs, including Sertaline. CHEK1, a highly evolutionary conserved serine/threonine-specific protein kinase, preserves the genome integrity by regulating DNA damage and cell cycle checkpoint responses.