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

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

Research output: Contribution to journalReview articlepeer-review

8 Citations (Scopus)


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.

Original languageEnglish
Article number111138
JournalBiomedicine and Pharmacotherapy
Publication statusPublished - Mar 2021


  • Antiviral drugs
  • Chloroquine
  • Endosomal escape
  • Hydroxychloroquine
  • Lysosomotropic drugs
  • Sars-CoV-2


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