Figure 1.

Coronavirus (SARS-CoV-2) structure, replication mechanism and possible actions of CQ/HCQ. SARS-CoV-2 is a positive-sense single-stranded RNA virus. The nuclear material is encapsulated by proteins in the form of a helical nucleocapsid, which is surrounded by a lipid envelope. (A) The virus contains different structural proteins, such as open reading frame polyproteins, spike glycoprotein (S; 1273 amino acids [aa]), an envelope protein (E; 75 aa), membrane protein (M; 222 aa), and nucleocapsid protein (N; 419 aa) [7]. G, glycosylation site. (B) SARS-CoV-2 entry and infection of the lungs. (C) SARS-CoV-2 enters the host cells (preferably lung epithelial) via ACE2 receptors. After fusion with the cell and lysosomal membrane, and following uncoating of the viral nucleocapsid in the cytoplasm, replication of the virus begins. Subsequently, the single-stranded RNA is replicated into complete virions by using the host cell nuclear, ER, and Golgi machinery. Virus release is mediated by exocytosis. Chloroquine inhibits autophagy by increasing the lysosomal pH. By creating a basic pH in the lysosomes, chloroquine inhibits the enzymatic activity of lysosomal enzymes and prevents the fusion of viral-lysosomal membranes. ACE2, angiotensin I converting enzyme 2; CQ, chloroquine; HCQ, hydroxychloroquine; ER, endoplasmic reticulum; HE, hemagglutinin-esterase; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TMPRSS2, transmembrane serine protease 2