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\begin{document}

\title{Tissue distributions of antiviral drugs impact on their capabilities of
reducing viral loads in COVID-19 treatment}



\author[1]{Yan WANG}%
\author[2]{Lei Chen}%
\affil[1]{Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences}%
\affil[2]{Rutgers University}%


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  \date{May 25, 2024}


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\begin{abstract}
Background and Purpose Previously we reported our hypothesis that the
high distribution of antiviral drugs in the lung is a key factor that
results in reducing viral loads in COVID-19 patients. So far,
chloroquine, lopinavir, hydroxychloroquine, azithromycin, favipiravir,
ribavirin, darunavir, remdesivir, and umifenovir have been tested in
COVID-19 clinical trials. Here we validate our hypothesis by comparing
the pharmacokinetics profiles of these drugs and their capabilities of
reducing viral load in clinical trials. Experimental approach The
RNA-seq data were obtained from public database and re-analyzed and
visualized by Single Cell Portal and Seurat. The tissue/plasma ratio of
antiviral drugs were calculated by AUC or Mean values that were compiled
from publications. Key Results High expression of both ACE2 and TMPRSS2
makes the lung and intestine vulnerable to SARS-CoV-2.
Hydroxychloroquine, chloroquine, and favipiravir, which were highly
distributed to the lung, were reported to reduce viral loads in
respiratory tract of COVID-19 patients. Conversely, drugs with poor lung
distributions, including lopinavir/ritonavir, umifenovir and remdesivir,
were insufficient to inhibit SARS-CoV-2 replication. Lopinavir/ritonavir
might inhibit SARS-CoV-2 in the GI tract according to their distribution
profiles. Conclusion and Implications The antiviral drugs should be
distributed straight to or accumulate in the lung for reducing viral
loads in respiratory tract of COVID-1 9 patients. Additionally, to
better evaluate antiviral drugs that target the intestine, the stool
samples should also be collected for viral RNA test in the future.%
\end{abstract}%



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\textbf{Hosted file}

\verb`BJP+manuscript.docx`  available at \url{https://authorea.com/users/311576/articles/467726-tissue-distributions-of-antiviral-drugs-impact-on-their-capabilities-of-reducing-viral-loads-in-covid-19-treatment}

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