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 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 IC 50 > 100 μM; dioscin and celastrol showed IC 50 = 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. 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 .
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into the cells through its spike proteins binding to human angiotensin-converting enzyme 2 (ACE2) protein and causes virus infection in host cells. Until now, there are no available antiviral drugs have been reported that can effectively block virus infection.The study aimed to discover the potential compounds to prevent viral spike proteins to bind to the human ACE2 proteins from Taiwan Database of Extracts and Compounds (TDEC) by structure-based virtual screening. In this study, to rapidly discover potential inhibitors against SARS-CoV-2 spike proteins, the molecular docking calculation was performed by AutoDock Vina program. Herein, we found that 39 potential compounds may have good binding affinities and can respectively bind to the viral receptor-binding domain (RBD) of spike protein in the prefusion conformation and spike-ACE2 complex protein in silico. Among those compounds, especially natural products thioflexibilolide A and candidine that were respectively isolated from the soft corals Sinularia flexibilis and Phaius mishmensis may have better binding affinity than others. This study provided the predictions that these compounds may have the potential to prevent SARS-CoV-2 spike protein from entry into cells.
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