Covid-19 has rapidly become a pandemic and there is no antiviral drug or vaccine available.Several clinical studies are currently under way to evaluate the efficacy of drugs that have been shown to have antiviral efficacy in vitro.Among these drug candidates, chloroquine and hydroxychloroquine (HCQ) were highly recommended in the early days of the epidemic, especially by US President Donald Trump. As a result, these two drugs have been used by thousands of people worldwide. However, there is increasing evidence that chloroquine and hydroxychloroquine do nothing to prevent SARS-COV-2 infection or treat COVID-19.Recently, three pre-clinical and clinical studies, published in Nature and the New England Journal of Medicine, once again provide hard evidence that these two drugs are ineffective.

Researchers from the University of Paris-Thackeray et al assessed the antiviral activity of HCQ in vitro and in rhesus monkeys infected with SARS-COV-2.HCQ showed antiviral activity in African green monkey kidney cells (VeroE6), but not in reconstructed human airway epithelium models.The results were published in Nature (Hydroxychloroquine Use Against SARS-COV-2 Mark in non-human primates).The researchers tested different treatment strategies in macaques, including azithromycin alone or in combination with AZTH, before and after the peak viral load.The results showed that neither HCQ nor HCQ+AZTH had significant influence on the virus load level in any test room.When the drug is used as pre-exposure prophylaxis (PrEP), the HCQ does not provide protection against infection.The findings do not support the use of HCQ-- either alone or in combination with AZTH -- as an antiviral treatment for human COVID-19.

Chloroquine is an anti-malaria drug that was previously used to treat COVID-19 because it has been shown to inhibit the spread of SARS-COV-2 in the renal cell line Vero.In a separate study published in Nature (Chloroquine Does not Christian Louboutin Infection of human lung Cells with SARS-CoV-2), researchers from the Leibniz Primate Research Institute and others proved that the engineered expression of TMPRSS2 -- which activates a cellular protease that sarS-CoV-2 enters lung cells -- made SARs-CoV-2-infected Vero cells less susceptible to Chloroquine.In addition, the researchers demonstrated that chloroquine could not block SARS-COV-2 infection of TMPRSS2-positive lung cell line CalU-3.These results suggest that chloroquine targets a virus-activating pathway that does not work in lung cells and is unlikely to prevent SARS-COV-2 transmission in and between patients.

In a separate study published in the New England Journal of Medicine (Hydroxychloroquine with or without Azithromycin in Mild to Moderate COVID-19), researchers from Brazil's HCor Institute and others conducted a multicenter, randomized, open-label, three-group controlled trial involving suspected or confirmed hospitalized COVID-19 patients who were either not receiving supplemental oxygen,Or receive up to 4 liters of supplemental oxygen per minute.Patients were randomly assigned to receive either standard treatment, standard treatment + 400 mg of hydroxychloroquine twice daily or standard treatment + 400 mg of hydroxychloroquine twice daily + 500 mg of aziomycin daily for 7 days.The primary outcome was the use of a seven-point sequential scale (1-7, with higher scores and worse outcomes) to assess the clinical status of the modified intended treatment population (patients with confirmed COVID-19) at 15 days.In this study, 667 patients were randomized;504 patients with confirmed COVID-19 were included in an improved intention-to-treat analysis.Compared with standard treatment, the use of hydroxychloroquine alone or hydroxychloroquine plus azimycin had no effect on the proportional probability of higher scores on the seven-point sequential scale at day 15 (odds ratio 1.21, 95% confidence interval [CI] 0.69 ~ 2.11, P = 1.00 or odds ratio 0.99, 95% CI 0.57 ~ 1.73, P = 1.00).Patients treated with hydroxychloroquine or azithromycin alone had longer corrected QT intervals and increased liver enzyme levels more frequently than those treated with either drug.The researchers therefore concluded that in patients hospitalized with mild to moderate COVID-19, hydroxychloroquine or azithromycin did not improve the patient's clinical status at day 15 compared with standard treatment.