PMC:7352545 / 72762-74228
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7352545","sourcedb":"PMC","sourceid":"7352545","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7352545","text":"CLQ and CLQ-OH are under investigation worldwide to treat COVID-19 (Figure 10). CLQ and its derivative CLQ-OH block CoV replication, amplification and spread in in vitro culture via inhibition of ACE2 receptor glycosylation. In HCoVs, interaction of the S glycoprotein with gangliosides initially occur as the first entry step during the replication cycle of the virus. CLQ and CLQ-OH have been alternative drugs for RA and several autoimmune diseases for 70 years, although they are anti-malaria prophylaxis drugs. CLQ-OH is an aminoquinoline with less toxicity than CLQ. CLQ-OH bears an N-hydroxyethyl side chain, which increases its solubility compared to CLQ [141]. CLQ-OH modulates activated immune cells via downregulation of TLR signaling and IL-6 production [142]. Clinical trials are also under consideration for the efficacy and safety of these drugs. Regarding the action mechanism(s), CLQ and CLQ-OH-mediated inhibition of ACE2 terminal glycosylation was considered. In in vitro Vero E6 cells, CLQ significantly inhibits SARS-CoV spread by interfering with ACE2 function, acting at the entry and post-entry steps of SARS-CoV-2 replication and infection. The binding affinity of ACE2 to S glycoprotein is simulated to be lowered by treatment with CLQ-OH or CLQ. CLQ may modify the binding affinity between ACE2 and S glycoprotein by alterations in ACE2 glycosylation or modification. CLQ-OH (EC50 0.72 μM) and CLQ (EC50, 5.47 μM) inhibit SARS-CoV-2 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