Mechanisms of action of 4-aminoquinoline compounds on viral infection.
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4-Aminoquinolines show in vitro antiviral effects against Sars-CoV-2.
Chiral switch of CQ/HCQ by simple enantiomers can improve their antiviral effects.
Cardiac disorders associated with CQ/HCQ can also be reduced using chiral switch.
Potential use of CQ/HCQ with other antiviral drugs might be considered.
Antiviral effects by 4-aminoquinolines mainly occurs in the early stages.
In 1918, quinine was used as one of the unscientifically based treatments against the H1N1 virus during the Spanish flu pandemic. Originally, quinine was extracted from the bark of Chinchona trees by South American natives of the Amazon forest, and it has been used to treat fever since the seventeenth century. The recent COVID-19 pandemic caused by Sars-Cov-2 infection has forced researchers to search for ways to prevent and treat this disease. Based on the antiviral potential of two 4-aminoquinoline compounds derived from quinine, known as chloroquine (CQ) and hydroxychloroquine (HCQ), clinical investigations for treating COVID-19 are being conducted worldwide. However, there are some discrepancies among the clinical trial outcomes.Thus, even after one hundred years of quinine use during the Spanish flu pandemic, the antiviral properties promoted by 4-aminoquinoline compounds remain unclear. The underlying molecular mechanisms by which CQ and HCQ inhibit viral replication open up the possibility of developing novel analogs of these drugs to combat COVID-19 and other viruses.Le texte complet de cet article est disponible en PDF.
Keywords : Sars-CoV-2, Antiviral drugs, Chloroquine, Hydroxychloroquine, Endosomal escape, Lysosomotropic drugs