4-Aminoquinoline compounds from the Spanish flu to COVID-19

Bazotte, Roberto Barbosa; Hirabara, Sandro Massao; Serdan, Tamires Afonso Duarte; Gritte, Raquel Bragante; Souza-Siqueira, Talita; Gorjao, Renata; Masi, Laureane Nunes; Antunes, Marina Masetto; Cruzat, Vinicius; Pithon-Curi, Tania Cristina; Curi, Rui

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.