Hydroxychloroquine for the management of COVID-19: Hope or Hype? A Systematic review of the current evidence

Umesh Devappa Suranagi; Harmeet Singh Rehan; Nitesh Goyal

Relatively lesser toxicity profile and fewer drug-drug interactions make HCQ an attractive candidate for testing for the antiviral properties. Various broad spectrum antiviral mechanisms of HCQ are proposed viz. change in the pH at the surface of the cell membrane, inhibition of nucleic acid replication, glycosylation of viral proteins, disruption of virus assembly, interruption of viral transport, inhibition of the viral release etc. 41 Previously during the SARS outbreak, HCQ was shown to exhibit anti-SARS CoV effect in an in-vitro study. 20 In this background, Yao et al, assessed the pharmacological activity of chloroquine and hydroxychloroquine using SARS-CoV-2 infected Vero cells. Further as continued part of the study, they simulated physiologically-based pharmacokinetic models (PBPK) on the in vitro data obtained. The researchers found HCQ to be more potent than chloroquine to inhibit SARS -CoV-2 in vitro. Based on PBPK extrapolation, they recommended a loading dose of 400 mg twice daily of HCQ sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days. 21 In another correspondence report letter of an in-vitro study by Liu et al, the investigators used VeroE6 cells and compared the antiviral activity of Chloroquine versus HCQ against SARS-CoV-2 to determine different multiplicities of infection (MOIs) by quantification of viral RNA copy numbers. They found out that 50% maximal effective concentration (EC50) for HCQ was significantly higher than chloroquine and HCQ can efficiently inhibit SARS-CoV-2 infection in vitro. 22 Previously in 2006, French researchers demonstrated that Chloroquine and HCQ effectively inhibit both human and feline SARS COV in the infected Vero cells. EC50 for HCQ was significantly higher than chloroquine. 20 The in-vitro studies using cell culture models demonstrate considerable anti-corona viral activity of HCQ, particularly against SARS CoV2. (Table 1)