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SUMMARY

The authors evaluate the cytotoxicity and the antiviral effect of Hydroxychloroquine (HCQ) against SARS-CoV-2 in comparison to Chloroquine (CQ) in vitro. While they show no difference in the cytotoxicity between these two drugs, they found that the anti-SARS-CoV-2 activity of HCQ is less potent compared to CQ. The author also showed that both drugs inhibit the release of the viral genome. This study, together with several other studies, propose the use of HCQ which shows less toxicity in human cells compared to CQ for the treatment of Covid-19.

RESEARCH HIGHLIGHTS

  1. HCQ anti-SARS-CoV-2 activity is less potent than CQ for a range of viral loads tested.
  2. HCQ and CQ both inhibited the release of the viral genome by blocking the transport of the SARS-CoV-2 from the early endosomal (EEs) to the endolysosomes (ELs).
  3. HCQ and CQ might have distinct modes of action, as HCQ reduces the number and the size of the ELs, while CQ disturbs the vesicle structure of ELs. This could be considered as a novelty of this study, however more experiments are needed to confirm the data.

RESEARCH IMPACT

At the moment this study has a very low impact for the treatment of SARS-COV-2 positive individuals, as this is an in vitro study for which monkey kidney cells were used. Moreover, there are already published clinical trials for HCQ. Example: Gautret, P., Lagier, J.C., Parola, P., Meddeb, L., Mailhe, M., Doudier, B., Courjon, J., Giordanengo, V., Vieira, V.E., Dupont, H.T. and Honoré, S., 2020. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents, p.105949, summarised elsewhere in this literature digest.)

METHODOLOGY

In vitro assays only using Vero E6 cells

CCK8 kit (cell viability)

qRT-PCR

Confocal Microscopy

STRENGTHS AND WEAKNESSES OF THE PAPER

Strengths:

  • Use of a readily available drug.
  • Reproducibility should be easy lab to lab.

Weaknesses:

  • Use of SARS-CoV-2 infection to model response instead of Covid-19.
  • Similar data by ( Yao, X., Ye, F., Zhang, M., Cui, C., Huang, B., Niu, P., Liu, X., Zhao, L., Dong, E., Song, C. and Zhan, S., 2020. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical Infectious Diseases.
  • In vitro only.
  • Using monkey kidney cells instead of human cells.
  • Low numbers of replicates
  • IFA of epi images is qualitative not quantitative.