Journal
VIROLOGY JOURNAL
Volume 14, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s12985-017-0724-6
Keywords
Benzo-heterocyclic amine derivative; IMPDH; Influenza A virus
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Funding
- National Natural Science Foundation of China [81273439]
- CAMS Initiative for Innovative Medicine [CAMS-I2M-1-010]
- Central Public-interest Scientific Institution Basal Research Fund [IMBF201410]
- National Science and Technology Major Project of the Ministry of Science and Technology of China [2012ZX10004501-004-001]
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Backgroud: Influenza virus is still a huge threat to the world-wide public health. Host inosine-5'-monophosphate dehydrogenase (IMPDH) involved in the synthesis of guanine nucleotides, is known to be a potential target to inhibit the replication of viruses. Herein, we evaluated antiviral activity of a benzo-heterocyclic amine derivative N30, which was designed to inhibit IMPDH. Results: The results demonstrated that N30 inhibited the replication of H1N1, H3N2, influenza B viruses, including oseltamivir and amantadine resistant strains in vitro. Mechanistically, neuraminidase inhibition assay and hemagglutination inhibition assay suggested that N30 did not directly target the two envelope glycoproteins required for viral adsorption or release. Instead, the compound could depress the activity of IMPDH type II. Based on these findings, we further confirmed that N30 provided a strong inhibition on the replication of respiratory syncytial virus, coronavirus, enterovirus 71 and a diverse strains of coxsackie B virus. Conclusions: We identified the small molecule N30, as an inhibitor of IMPDH, might be a potential candidate to inhibit the replication of various viruses.
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