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Lung tissue distribution of drugs as a key factor for COVID-19 treatment
  • Yan WANGOrcid,
  • Lei Chen
Yan WANG
Orcid
Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences
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Lei Chen
Rutgers The State University of New Jersey
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Peer review status:ACCEPTED

08 Apr 2020Submitted to British Journal of Pharmacology
14 Apr 2020Submission Checks Completed
14 Apr 2020Assigned to Editor
14 Apr 2020Reviewer(s) Assigned
21 Apr 2020Editorial Decision: Revise Minor
24 Apr 20201st Revision Received
27 Apr 2020Submission Checks Completed
27 Apr 2020Assigned to Editor
29 Apr 2020Reviewer(s) Assigned
30 Apr 2020Editorial Decision: Accept

Abstract

Lopinavir combined with ritonavir were reported to benefit the patients with SARS by reducing the viral loads. However, in the latest clinical trials, no benefit was observed with lopinavir-ritonavir treatment beyond standard care in patients with COVID-19. We comment here that this disappointed result of clinical trial might result from the low volume of the lung distribution of lopinavir. The major reasons were listed below: 1) The binding affinity of ACE2 with SARS-CoV-2 spike protein is ~10- to 20-fold higher than the binding affinity of ACE2 with SARS-CoV spike protein, indicating that SARS-CoV-2 can enter AT2 cells in lung much easier than SARS-CoV. Therefore, the viral loads of SARS-CoV-2 might be much higher than viral loads of SARS-CoV in the lung tissue. 2) The concentration of lopinavir in the lung tissue was 1.18 μg equiv/ml in rats. The low volume of the lung distribution of lopinavir might not be enough to inhibit the coronavirus replication due to the high viral loads in the lung tissue. 3) In contrast, the concentration of chloroquine in the lung tissue was much higher (30.76 ± 0.85 μg equiv/ml) in rats, which might lead to its clinical and virologic benefits in the treatment of COVID-19 patients. Together, we proposed here that anti-SARS-CoV-2 drug repurposing studies should pay more attentions to the lung tissue distribution of antiviral drugs. The efficacy of antiviral drugs might depend on their lung tissue distributions