Network-based Drug Repurposing for Human Coronavirus

Yadi Zhou; Yuan Hou; Jiayu Shen; Yin Huang; William Martin; Feixiong Cheng

Anti-inflammatory agents. Inflammatory pathways play essential roles in viral infections [53, 54] . As a biogenic amine, melatonin (N-acetyl-5-methoxytryptamine) (Z = -1.72 and GSEA score = 2) plays a key role in various biological processes, and offers a potential strategy in the management of viral infections [55, 56] . Viral infections are often associated with immune-inflammatory injury, in which the level of oxidative stress increases significantly and leaves negative effects on multiple organ functions [57] . The antioxidant effect of melatonin makes it a putative candidate drug to relieve patients' clinical symptoms in antiviral treatment, even though melatonin cannot eradicate or even curb the viral replication or transcription [58, 59] . In addition, the application of melatonin may prolong patients' survival time, which may provide a chance for patients' immune systems to recover and eventually eradicate the virus. As shown in Figure 5E , melatonin indirectly targets several HCoV cellular targets, including ACE2, BCL2L1, JUN, and IKBKB. Eplerenone (Z = -1.59), an aldosterone receptor antagonist, is reported to have a similar anti-inflammatory effect as melatonin. By inhibiting mast-cellderived proteinases and suppressing fibrosis, eplerenone can improve survival of mice infected with encephalomyocarditis virus [60] .