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

Background and aim: 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. Methods: 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. Results and conclusion: 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 (K-d) = 0.468 mu M, 1.712 mu M, 6.650 mu M, 2.86 mu M, 3.761 mu M and 4.27 mu M, 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 mu M; dioscin and celastrol showed IC50 =1.5625 mu M and 0.9866 mu M, respectively. These natural products may bind to the viral spike protein, preventing SARS-CoV-2 from entering cells. Section: 1: Natural Products. Taxonomy (classification by evise): SARS-CoV-2, Structure-Based Virtual Screening, Isothermal Titration Calorimetry and Lentivirus Particles Pseudotyped (Vpp) Infection Assay, in silico and in vitro study. (C) 2021 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.

Automated summary

This study identified 39 natural products from the Taiwan Database of Extracts and Compounds that can potentially prevent the binding of viral spike proteins with human ACE2 proteins, thus blocking the entry of SARS-CoV-2 into cells. In silico and in vitro experiments demonstrated the binding affinities of these natural products and their inhibitory effects on viral infection.