Potential therapeutic approaches for the early entry of SARS-CoV-2 by interrupting the interaction between the spike protein on SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2)

Abstract

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly spread around the globe. At present, there is no precise and effective treatment for the patients with COVID-19, so rapid development of drugs is urgently needed in order to contain the highly infectious disease. The virus spike protein (S protein) can recognize the angiotensin-converting enzyme 2 (ACE2) receptor on the host cell membrane and undergo a series of conformational changes, protease cleavage and membrane fusion to complete the virus entry, so S protein is an important target for vaccine and drug development. Here we provide a brief overview of molecular mechanisms of virus entry, as well as some potential antiviral agents that act on S/ACE2 protein-protein interaction. Specifically, we focused on experimentally validated and/or computational prediction identified inhibitors that target SARS-CoV-2 S protein, ACE2 and enzymes associated with viral infection. This review offers valuable information for the discovery and development of potential antiviral agents in combating SARS-CoV-2. In addition, with the deepening understanding of the mechanism of SARS-CoV-2 infection, more targeted prevention and treatment drugs will be explored with the aid of the advanced technology in the future.

Keywords: Angiotensin-converting enzyme 2; COVID-19; Cell entry; Protein–protein interaction (PPI) inhibitors; SARS-CoV-2; Spike protein.