2. Academic Validation
  3. A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity

A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity

  • Acta Pharmacol Sin. 2024 Jul 10. doi: 10.1038/s41401-024-01331-7.
Yin-Yan Li 1,  Guo-Dong Liang 2,  Zhi-Xuan Chen 1,  Ke Zhang 3,  Jin-Long Liang 1,  Lin-Rui Jiang 1,  Si-Zu Yang 1,  Feng Jiang 1,  Shu-Wen Liu 1,  Jie Yang 4
Affiliations

Affiliations

  • 1 NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 2 Key Laboratory for Candidate Drug Design and Screening Based on Chemical Biology, College of Pharmacy, Inner Mongolia Medical University, Huhhot, 010110, China.
  • 3 Key Laboratory of Microbio and Infectious Disease Prevention & Control in Guizhou Province/Institute of Virology, School of Basic Medicine, Guizhou Medical University, Guiyang, 561113, China.
  • 4 NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. yj528@smu.edu.cn.
PMID: 38987389 DOI: 10.1038/s41401-024-01331-7
Abstract

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available Antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum Antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum Antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited Infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV Infection mainly through specific interactions with the Influenza Virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

Keywords

antiviral activity; entry inhibitor; hemagglutinin; influenza A virus; small molecule compound.

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