2. Academic Validation
  3. Nine-valent oleanolic acid conjugates as potent inhibitors blocking the entry of influenza A virus

Nine-valent oleanolic acid conjugates as potent inhibitors blocking the entry of influenza A virus

  • Eur J Med Chem. 2023 Oct 5:258:115562. doi: 10.1016/j.ejmech.2023.115562.
Liang Shao 1,  Yangqing Su 1,  Yuan Zhang 1,  Fan Yang 1,  Jihong Zhang 1,  Tao Tang 2,  Fei Yu 3
Affiliations

Affiliations

  • 1 Medical School of Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
  • 2 Medical School of Kunming University of Science and Technology, Kunming, Yunnan, 650500, China. Electronic address: [email protected].
  • 3 Medical School of Kunming University of Science and Technology, Kunming, Yunnan, 650500, China; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. Electronic address: [email protected].
PMID: 37354741 DOI: 10.1016/j.ejmech.2023.115562
Abstract

The influenza pandemic remains a major public health challenge that endangers the lives of many vulnerable and immune-compromised individuals worldwide. The high infectivity and genetic variability of Influenza Virus make it particularly challenging to design effective drugs to inhibit the virus. In previous studies, we determined that oleanolic acid (OA) and its derivatives block interactions between influenza and host cells, thus endowing OA with anti-viral efficacy. Inspired by the role of cluster glycosides in the interactions between hemagglutinins (HA) and sialic acid receptors (SA), we designed and synthesized a series of OA nonamers via the CuAAC reaction, and evaluated their anti-viral activities in vitro. We determined that among these nonamers, compound 15 displayed the highest potency (IC50 = 5.23 μM), equivalent to the Antiviral drug oseltamivir which is routinely prescribed for influenza A virus strain A/WSN/33 (H1N1). In addition, these compounds also displayed Antiviral activity against influenza B. Mechanistic experiments indicated that OA nonamers can effectively target the influenza HA protein. This study collectively demonstrates that multivalent structure-activity binding strategy is an effective method for designing Influenza Virus inhibitors.

Keywords

Entry inhibitor; Hemagglutinin; Influenza A virus; Nonamer; Oleanolic acid.

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