Potential natural products that target the SARS-CoV-2 spike protein identified by structure-based virtual screening, isothermal titration calorimetry and lentivirus particles pseudotyped (Vpp) infection assay

Guan-Yu Chen; Yi-Cheng Pan; Tung-Ying Wu; Tsung-You Yao; Wei-Jan Wang; Wan-Jou Shen; Azaj Ahmed; Shu-Ting Chan; Chih-Hsin Tang; Wei-Chien Huang; Mien-Chie Hung; Juan-Cheng Yang; Yang-Chang Wu

doi:10.1016/j.jtcme.2021.09.002

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Potential natural products that target the SARS-CoV-2 spike protein identified by structure-based virtual screening, isothermal titration calorimetry and lentivirus particles pseudotyped (Vpp) infection assay

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Potential natural products that target the SARS-CoV-2 spike protein identified by structure-based virtual screening, isothermal titration calorimetry and lentivirus particles pseudotyped (Vpp) infection assay

Guan-Yu Chen, Yi-Cheng Pan, Tung-Ying Wu, Tsung-You Yao, Wei-Jan Wang, Wan-Jou Shen, Azaj Ahmed, Shu-Ting Chan, Chih-Hsin Tang, Wei-Chien Huang, …

Journal of traditional and complementary medicine, Vol.12(1), pp.73-89

01/01/2022

DOI: 10.1016/j.jtcme.2021.09.002

PMID: 34549024

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells through the binding of the viral spike protein with human angiotensin-converting enzyme 2 (ACE2), resulting in the development of coronavirus disease 2019 (COVID-19). To date, few antiviral drugs are available that can effectively block viral infection. This study aimed to identify potential natural products from Taiwan Database of Extracts and Compounds (TDEC) that may prevent the binding of viral spike proteins with human ACE2 proteins. The structure-based virtual screening was performed using the AutoDock Vina program within PyRX software, the binding affinities of compounds were verified using isothermal titration calorimetry (ITC), the inhibitions of SARS-CoV-2 viral infection efficacy were examined by lentivirus particles pseudotyped (Vpp) infection assay, and the cell viability was tested by 293T cell in MTT assay. We identified 39 natural products targeting the viral receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in silico. In ITC binding assay, dioscin, celastrol, saikosaponin C, epimedin C, torvoside K, and amentoflavone showed dissociation constant (Kd) = 0.468 μM, 1.712 μM, 6.650 μM, 2.86 μM, 3.761 μM and 4.27 μM, respectively. In Vpp infection assay, the compounds have significantly and consistently inhibition with the 50–90% inhibition of viral infection efficacy. In cell viability, torvoside K, epimedin, amentoflavone, and saikosaponin C showed IC50 > 100 μM; dioscin and celastrol showed IC50 = 1.5625 μM and 0.9866 μM, respectively. These natural products may bind to the viral spike protein, preventing SARS-CoV-2 from entering cells. Natural Products. SARS-CoV-2, Structure-Based Virtual Screening, Isothermal Titration Calorimetry and Lentivirus Particles Pseudotyped (Vpp) Infection Assay, in silico and in vitro study. [Display omitted]

Isothermal titration calorimetry

Lentivirus particles pseudotyped (Vpp) infection assay

SARS-CoV-2

Spike protein

Virtual screening

Details

Title: Subtitle: Potential natural products that target the SARS-CoV-2 spike protein identified by structure-based virtual screening, isothermal titration calorimetry and lentivirus particles pseudotyped (Vpp) infection assay
Creators: Guan-Yu Chen - Chinese Medicine Research and Development Center, Sex Hormone Research Center, Department of Obstetrics and Gynecology, Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
Yi-Cheng Pan - Chinese Medicine Research and Development Center, Sex Hormone Research Center, Department of Obstetrics and Gynecology, Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
Tung-Ying Wu - Meiho University
Tsung-You Yao - Kaohsiung Medical University
Wei-Jan Wang - Department of Biological Science and Technology, Research Center for Cancer Biology, New Drug Development Center, China Medical University, Taichung, Taiwan
Wan-Jou Shen - Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan
Azaj Ahmed - China Medical University
Shu-Ting Chan - TCI (Taiwan)
Chih-Hsin Tang - Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
Wei-Chien Huang - Chinese Medicine Research and Development Center, Sex Hormone Research Center, Department of Obstetrics and Gynecology, Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
Mien-Chie Hung - Chinese Medicine Research and Development Center, Sex Hormone Research Center, Department of Obstetrics and Gynecology, Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
Juan-Cheng Yang - Chinese Medicine Research and Development Center, Sex Hormone Research Center, Department of Obstetrics and Gynecology, Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
Yang-Chang Wu - Chinese Medicine Research and Development Center, Sex Hormone Research Center, Department of Obstetrics and Gynecology, Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
Resource Type: Journal article
Publication Details: Journal of traditional and complementary medicine, Vol.12(1), pp.73-89
DOI: 10.1016/j.jtcme.2021.09.002
PMID: 34549024
ISSN: 2225-4110
eISSN: 2225-4110
Publisher: Elsevier Taiwan LLC
Number of pages: 17
Language: English
Date published: 01/01/2022
Academic Unit: Internal Medicine
Record Identifier: 9985178667602771

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