Coronavirus biology. Notable coronavirus structural proteins include the spike protein (S), which mediates receptor binding and fusion, the viral membrane protein (M), and the nucleocapsid protein (N). After binding of the viral spike protein to the angiotensin converting enzyme-2 (ACE2) receptor, virions enter cells either by receptor-mediated endocytosis or direct fusion with the cell membrane.15 Endocytosis is a potential target of chloroquine, which prevents endosomal acidification that triggers viral membrane fusion. Chloroquine may also modify ACE2 terminal glycosylation and inhibit coronavirus binding. Viral RNA is then transcribed to generate polyproteins pp1a and pp1ab that are cleaved by a protease to generate the viral replication machinery. These polyproteins are cleaved to form replication-transcription protein complexes (RTCs) by a viral protease 3-chymotrypsin-like protease (3CLpro). 3CLpro has been postulated to be a target of human immunodeficiency virus protease inhibitors lopinavir or ritonavir, although in silico studies have questioned this theory.108 Viral RNA is replicated and transcribed in double membraned vesicles (DMV) in replication-transcription protein complexes, which include the RNA-dependent RNA polymerase that is the putative target of remdesivir. Viral mRNA is then translated and virions are assembled in the endoplasmic reticulum and golgi.
