7YSX

Crystal structure of PDE4D complexed with licoisoflavone A

Summary for 7YSX

• Entry DOI: 10.2210/pdb7ysx/pdb
• Descriptor: cAMP-specific 3',5'-cyclic phosphodiesterase 4D, ZINC ION, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: pde4d, complex, licoisoflavone a, inhibitor, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 81391.18

Authors

Liu, J.Y.,Li, M.J.,Xu, Y.C. (deposition date: 2022-08-13, release date: 2023-07-12, Last modification date: 2023-11-29)

Primary citation

Xu, H.,Li, S.,Liu, J.,Cheng, J.,Kang, L.,Li, W.,Zhong, Y.,Wei, C.,Fu, L.,Qi, J.,Zhang, Y.,You, M.,Zhou, Z.,Zhang, C.,Su, H.,Yao, S.,Zhou, Z.,Shi, Y.,Deng, R.,Lv, Q.,Li, F.,Qi, F.,Chen, J.,Zhang, S.,Ma, X.,Xu, Z.,Li, S.,Xu, Y.,Peng, K.,Shi, Y.,Jiang, H.,Gao, G.F.,Huang, L.
Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19.
Proc.Natl.Acad.Sci.USA, 120:e2301775120-e2301775120, 2023

PubMed Abstract: The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main protease (M), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54 Å and 1.65 Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.

PubMed: 37094153
DOI: 10.1073/pnas.2301775120

Experimental method

X-RAY DIFFRACTION (1.65 Å)