Discovery and SAR Research for Antivirus Activity of Novel Butenolide on Influenza A Virus H1N1 In Vitro and In Vivo

Zhenya Wang; Xiaoning Hu; Yuanyuan Li; Xiaodong Mou; Congcong Wang; Xinli Chen; Yayun Tan; Chunli Wu; Hongmin Liu; Haiwei Xu

doi:10.1021/acsomega.9b01421

Discovery and SAR Research for Antivirus Activity of Novel Butenolide on Influenza A Virus H1N1 In Vitro and In Vivo

ACS Omega. 2019 Aug 2;4(8):13265-13269. doi: 10.1021/acsomega.9b01421. eCollection 2019 Aug 20.

Authors

Affiliation

¹ Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education and Key Laboratory of "Runliang" Antiviral Medicines Research and Development, Institute of Drug Discovery & Development, Zhengzhou University, No. 100, KeXueDaDao, Zhengzhou 450001, China.

Abstract

Influenza viruses (IV) cause substantial morbidity and mortality through routine seasonal spread and epidemics. A novel series of butenolides were discovered to be able to inhibit influenza H1N1 activity in vitro, and the SAR for anti-influenza activity was investigated. By optimization of the hit compound, compound 37 was obtained with an EC₅₀ of 6.7 μM against influenza A virus H1N1 as an inhibitor of NA and with low cytotoxicity on MDCK cells. Also, it can inhibit the expression of the influenza A virus gene in the lung of SPF KM mice to show antivirus activity in vivo. These results suggested that compound 37 could inhibit the influenza A virus H1N1 via targeting NA.