Figure 1.

Highlights of SARRS-CoV-2 lifecycle and proposed mechanisms of CQ/HCQ interruption of virulence: 1) modulation of endosome or lysosome function by elevation of pH, thereby interrupting virus entry, as acidic pH is required for glycosyltransferases to modify envelope glycoprotein. CQ/HCQ impairs viral spike proteins binding with ACE2 receptors, thereby blocking virus-host cell fusion; Note that solid black arrows indicate the critical phases by which CQ/HCQ may disrupt the lifecycle of coronavirus (A). 2) Modulation of cytokine production (TNFα, etc.) and antigen presentation. The typical innate response to SARS-CoV-2 is marked by type I interferon. The anti-inflammatory property is proved effective for rheumatoid arthritis and lupus (B); 3) Intervention of intracellular calcium gradients, impairing RNA replication, spike glycoprotein production, and innate inflammatory response. Alternatively, attenuation of Ca²⁺ influx through viroporin (Green arrow) to mediate proinflammation (B). ER. Endoplasmic reticulum; hACE2, human angiotensin-converting enzyme 2; TNFα, tumor necrosis factor α.