Immunosuppressant or antineoplastic agents
Previous studies have confirmed the mammalian target of rapamycin complex 1 (mTORC1) as the key factor in regulating various viruses’ replications, including Andes orthohantavirus and coronavirus48,49. Sirolimus (Z = –2.35 and GSEA score = 3), an inhibitor of mammalian target of rapamycin (mTOR), was reported to effectively block viral protein expression and virion release effectively50. Indeed, the latest study revealed the clinical application: sirolimus reduced MERS-CoV infection by over 60%51. Moreover, sirolimus usage in managing patients with severe H1N1 pneumonia and acute respiratory failure can improve those patients’ prognosis significantly50. Mercaptopurine (Z = –2.44 and GSEA score = 1), an antineoplastic agent with immunosuppressant property, has been used to treat cancer since the 1950s and expanded its application to several auto-immune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and Crohn’s disease52. Mercaptopurine has been reported as a selective inhibitor of both SARS-CoV and MERS-CoV by targeting papain-like protease which plays key roles in viral maturation and antagonism to interferon stimulation53,54. Mechanistically, mercaptopurine potentially target several host proteins in HCoVs, such as JUN, PABPC1, NPM1, and NCL40,55 (Fig. 5d).