Allopregnanolone targets nucleoprotein as a novel influenza virus inhibitor

Meiyue Dong; Yanyan Wang; Ping Li; Zinuo Chen; Varada Anirudhan; Qinghua Cui; Lijun Rong; Ruikun Du

doi:10.1016/j.virs.2023.09.003

December 2023

Citation: Meiyue Dong, Yanyan Wang, Ping Li, Zinuo Chen, Varada Anirudhan, Qinghua Cui, Lijun Rong, Ruikun Du. Allopregnanolone targets nucleoprotein as a novel influenza virus inhibitor .VIROLOGICA SINICA, 2023, 38(6) : 931-939. http://dx.doi.org/10.1016/j.virs.2023.09.003

Allopregnanolone targets nucleoprotein as a novel influenza virus inhibitor

Meiyue Dong ^a ,
Yanyan Wang ^b ,
Ping Li ^b ,
Zinuo Chen ^a ,
Varada Anirudhan ^c ,
Qinghua Cui ^{a,d
,,} ,
Lijun Rong ^{c
,,} ,
Ruikun Du ^{a,d
,,}

a. Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China;
b. College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China;
c. Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, 60612, USA;
d. Qingdao Academy of Chinese Medical Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, 266122, China

Corresponding author: Qinghua Cui, cuiqinghua@sdutcm.edu.cn
Lijun Rong, lijun@uic.edu
Ruikun Du, ruikun@sdutcm.edu.cn
Received Date: 11 June 2023
Accepted Date: 19 September 2023
Available online: 22 September 2023

Abstract

Influenza A virus (IAV) poses a global public health concern and remains an imminent threat to human health. Emerging antiviral resistance to the currently approved influenza drugs emphasizes the urgent need for new therapeutic entities against IAV. Allopregnanolone (ALLO) is a natural product that has been approved as an antidepressant drug. In the present study, we repurposed ALLO as a novel inhibitor against IAVs. Mechanistic studies demonstrated that ALLO inhibited virus replication by interfering with the nucleus translocation of viral nucleoprotein (NP). In addition, ALLO showed significant synergistic activity with compound 16, a hemagglutinin inhibitor of IAVs. In summary, we have identified ALLO as a novel influenza virus inhibitor targeting NP, providing a promising candidate that deserves further investigation as a useful anti-influenza strategy in the future.
- Allopregnanolone (ALLO)
- , Antiviral
- , Influenza A virus (IAV)
- , Nucleoprotein
- , Nucleus translocation

Electronic Supplementary Material

10.1016j.virs.2023.09.003-ESM.docx
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