Design and Synthesis of Oleanolic Acid Trimers to Enhance Inhibition of Influenza Virus Entry

Author(s):  
Liang Shao ◽  
Fan Yang ◽  
Yangqing Su ◽  
Weijia Li ◽  
Jihong Zhang ◽  
...  
2020 ◽  
Vol 17 (9) ◽  
pp. 1084-1101
Author(s):  
Tingjuan Wu ◽  
Xu Yao ◽  
Guan Wang ◽  
Xiaohe Liu ◽  
Hongfei Chen ◽  
...  

Background: Oleanolic Acid (OA) is a ubiquitous product of triterpenoid compounds. Due to its inexpensive availability, unique bioactivities, pharmacological effects and non-toxic properties, OA has attracted tremendous interest in the field of drug design and synthesis. Furthermore, many OA derivatives have been developed for ameliorating the poor water solubility and bioavailability. Objective: Over the past few decades, various modifications of the OA framework structure have led to the observation of enhancement in bioactivity. Herein, we focused on the synthesis and medicinal performance of OA derivatives modified on A-ring. Moreover, we clarified the relationship between structures and activities of OA derivatives with different functional groups in A-ring. The future application of OA in the field of drug design and development also was discussed and inferred. Conclusion: This review concluded the novel achievements that could add paramount information to the further study of OA-based drugs.


2021 ◽  
Vol 14 (6) ◽  
pp. 587
Author(s):  
Zhaoyu Chen ◽  
Qinghua Cui ◽  
Michael Caffrey ◽  
Lijun Rong ◽  
Ruikun Du

Hemagglutinin (HA) plays a critical role during influenza virus receptor binding and subsequent membrane fusion process, thus HA has become a promising drug target. For the past several decades, we and other researchers have discovered a series of HA inhibitors mainly targeting its fusion machinery. In this review, we summarize the advances in HA-targeted development of small molecule inhibitors. Moreover, we discuss the structural basis and mode of action of these inhibitors, and speculate upon future directions toward more potent inhibitors of membrane fusion and potential anti-influenza drugs.


Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 895
Author(s):  
Mei Luo ◽  
Ximin Wu ◽  
Yiming Li ◽  
Fujiang Guo

Influenza outbreaks pose a serious threat to human health. Hemagglutinin (HA) is an important target for influenza virus entry inhibitors. In this study, we synthesized four pentacyclic triterpene conjugates with a sialylglycopeptide scaffold through the Cu(I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC) and prepared affinity assays of these conjugates with two HAs, namely H1N1 (A/WSN/1933) and H5N1 (A/Hong Kong/483/97), respectively. With a dissociation constant (KD) of 6.89 μM, SCT-Asn-betulinic acid exhibited the strongest affinity with the H1N1 protein. Furthermore, with a KD value of 9.10 μM, SCT-Asn-oleanolic acid exhibited the strongest affinity with the H5N1 protein. The conjugates considerably enhanced antiviral activity, which indicates that pentacyclic triterpenes can be used as a ligand to improve the anti-influenza ability of the sialylglycopeptide molecule by acting on the HA protein.


MedChemComm ◽  
2016 ◽  
Vol 7 (10) ◽  
pp. 1932-1945 ◽  
Author(s):  
Xu Han ◽  
Yongying Shi ◽  
Longlong Si ◽  
Zibo Fan ◽  
Han Wang ◽  
...  

A total of 24 novel sialic acid–pentacyclic triterpene conjugates were synthesized and evaluated as anti-influenza virus entry inhibitors.


PLoS ONE ◽  
2020 ◽  
Vol 15 (2) ◽  
pp. e0228735 ◽  
Author(s):  
Kelly Drews ◽  
Michael P. Calgi ◽  
William Casey Harrison ◽  
Camille M. Drews ◽  
Pedro Costa-Pinheiro ◽  
...  

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jihye Lee ◽  
Jinhee Kim ◽  
Kidong Son ◽  
Anne-Laure Pham Humg d’Alexandry d’Orengiani ◽  
Ji-Young Min

2007 ◽  
Vol 13 (4) ◽  
pp. 405-414 ◽  
Author(s):  
Hiroshi Kido ◽  
Yuushi Okumura ◽  
Hiroshi Yamada ◽  
Trong Quang Le ◽  
Mihiro Yano

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