Anti-inflammatory agents
Inflammatory pathways play essential roles in viral infections56,57. 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 infections58,59. Viral infections are often associated with immune-inflammatory injury, in which the level of oxidative stress increases significantly and leaves negative effects on the function of multiple organs60. 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 transcription61,62. 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 Fig. 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-cell-derived proteinases and suppressing fibrosis, eplerenone can improve survival of mice infected with encephalomyocarditis virus63.
In summary, our network proximity analyses offer multiple candidate repurposable drugs that target diverse cellular pathways for potential prevention and treatment of 2019-nCoV/SARS-CoV-2. However, further preclinical experiments64 and clinical trials are required to verify the clinical benefits of these network-predicted candidates before clinical use.