Molecular Insights into the MAPK Cascade during Viral Infection: Potential Crosstalk between HCQ and HCQ Analogues

Figure 2

Summary of the possible antiviral properties of CQ, HCQ, and analogues on the SARS-CoV-2 replication cycle. The broad antiviral spectrum of CQ, HCQ, and analogues may depend on their ability to interfere with (1) the early phases of viral infection, mediated by ACE2 and TMPRSS2, affecting the viral particles binding to their receptors—this occurs interfering with the biosynthesis of sialic acid [33] and with the glycosylation of either the spike protein itself [35] or the cell surface receptor ACE2 [36]; (2) the pH-dependent endocytosis of viral particles, by increasing the endosomal pH; (3) the low pH-dependent endosome-mediated viral entry of viruses and the lysosomal-dependent disruption of the viral particles; (4) the viral particle uncoating and release of nucleic acid and enzymes necessary for its replication; (5) the posttranslational modification of viral proteins, by blocking the low pH-dependent action of proteases and glycosyltransferases on viral envelope glycoproteins, within the trans-Golgi network vesicles; (6) the viral budding preventing the release of viral particles.