Chloroquine is effective against influenza A virus in vitro but not in vivo

Abstract

Background: Chloroquine is an inexpensive and widely available 9-aminoquinolone used in the management of malaria. Recently, in vitro assays suggest that chloroquine may have utility in the treatment of several viral infections including influenza.

Objectives: We sought to test whether chloroquine is effective against influenza in vivo in relevant animal models.

Methods: The effectiveness of chloroquine at preventing or ameliorating influenza following viral challenge was assessed in established mouse and ferret disease models.

Results: Although active against influenza viruses in vitro, chloroquine did not prevent the weight loss associated with influenza virus infection in mice after challenge with viruses expressing an H1 or H3 hemagglutinin protein. Similarly, clinical signs and viral replication in the nose of ferrets were not altered by treatment.

Conclusions: Although in vitro results were promising, chloroquine was not effective as preventive therapy in vivo in standard mouse and ferret models of influenza virus infection. This dampens enthusiasm for the potential utility of the drug for humans with influenza.

Figure 1

Effect of chloroquine (CQ) on influenza virus infection in mice. (A) Groups of nine mice were infected with influenza viruses PR8 (H1N1) or HK68 (H3N2), dosed with 12.5 mg/kg/day of chloroquine starting 24 hours prior to infection, and followed for weight loss (mean ± SD) compared to mock‐treated animals. (B) Groups of five mice were infected with HK68, dosed with either 25 or 37.5 mg/kg/day of chloroquine starting 24 hours prior to infection, and followed for weight loss compared to mock‐treated animals. An asterisk (*) indicates a significant difference in weight loss compared to the other groups at that time point (P < 0.05 by anova).

Figure 2

Effect of chloroquine (CQ) on influenza virus infection in ferrets. Groups of four ferrets were infected with Syd97 (H3N2), dosed with 10 mg/kg/day of chloroquine starting 24 hours prior to infection, and compared to untreated animals. (A) Rectal temperatures were monitored daily. Ferrets anesthetized with ketamine had 2 ml of sterile saline introduced into their noses to induce sneezing and the effluent captured in order to assay (B) protein content by the Bradford assay and (C) viral titer on MDCK cells. Values are presented as the mean ± SD. An asterisk (*) indicates a significant difference in viral titer compared to the other group at that time point (P < 0.05 by anova).