Fig. 1.
The Infectious Cycle of SARS-CoV-2 and Therapeutic Targets to Key Proteins. 1) The spike (S) protein of SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) receptor on the host cell membrane, with TMPRSS2 in close proximity to aid viral fusion. The virus then enters host cells via endocytosis. As of December 2020, two mRNA vaccines targeting the S protein (BNT162b2 and mRNA-1273) have been authorized for emergency use by the U.S. Food and Drug Administration (FDA) for the prevention of COVID-19. 2) Upon cell entry, the viral RNA of SARS-CoV-2 is released into the cytoplasm. 3) Translation of the viral RNA produces polyproteins (pp1a and pp1ab), which are cleaved by the main protease (Mpro) to form non-structural proteins (NSPs). 4) Transcription of the viral RNA results in several mRNAs that are translated into essential viral proteins, including S, M (membrane), E (envelope), and N (nucleocapsid). 5) RNA-dependent RNA polymerase (RdRp) catalyzes viral RNA replication for new viral particle assembly. Remdesivir acts as an RdRp inhibitor and is the first drug approved by the U.S. FDA to treat COVID-19. 6) Newly synthesized viral RNA is packaged into new viral particles with the essential viral proteins. 7) Vesicles carrying new viral particles fuse with the cell membrane, releasing the new virus from host cells.