Screening S protein – ACE2 blockers from natural products: Strategies and advances in the discovery of potential inhibitors of COVID-19

Abstract The Coronavirus disease, 2019 (COVID-19) is caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which poses a major threat to human life and health. Given its continued development, limiting the spread of COVID-19 in the population remains a challenging task. Currently, multiple therapies are being tried around the world to deal with SARS-CoV-2 infection, and a variety of studies have shown that natural products have a significant effect on COVID-19 patients. The combination of SARS-CoV-2 S protein with Angiotensin converting enzyme II(ACE2) of host cell to promote membrane fusion is an initial critical step for SARS-CoV-2 infection. Therefore, screening natural products that inhibit the binding of SARS-CoV-2 S protein and ACE2 also provides a feasible strategy for the treatment of COVID-19. Establishment of high throughput screening model is an important basis and key technology for screening S protein-ACE2 blockers. Based on this, the molecular structures of SARS-CoV-2 and ACE2 and their processes in the life cycle of SARS-CoV-2 and host cell infection were firstly reviewed in this paper, with emphasis on the methods and techniques of screening S protein-ACE2 blockers, including Virtual Screening (VS), Surface Plasmon Resonance (SPR), Biochromatography, Biotin-avidin with Enzyme-linked Immunosorbent assay and Gene Chip Technology. Furthermore, the technical principle, advantages and disadvantages and application scope were further elaborated. Combined with the application of the above screening technologies in S protein-ACE2 blockers, a variety of natural products, such as flavonoids, terpenoids, phenols, alkaloids, were summarized, which could be used as S protein-ACE2 blockers, in order to provide ideas for the efficient discovery of S protein-ACE2 blockers from natural sources and contribute to the development of broad-spectrum anti coronavirus drugs.