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