Tissue distributions of antiviral drugs affect their capabilities of reducing viral loads in COVID-19 treatment.
Identifieur interne : 000A75 ( Main/Corpus ); précédent : 000A74; suivant : 000A76Tissue distributions of antiviral drugs affect their capabilities of reducing viral loads in COVID-19 treatment.
Auteurs : Yan Wang ; Lei ChenSource :
- European journal of pharmacology [ 1879-0712 ] ; 2020.
English descriptors
- KwdEn :
- Angiotensin-Converting Enzyme 2 (biosynthesis), Antiviral Agents (pharmacokinetics), Antiviral Agents (pharmacology), COVID-19 (drug therapy), Humans (MeSH), Lung (metabolism), Pandemics (MeSH), SARS-CoV-2 (drug effects), Serine Endopeptidases (biosynthesis), Tissue Distribution (MeSH), Viral Load (drug effects).
- MESH :
- chemical , biosynthesis : Angiotensin-Converting Enzyme 2, Serine Endopeptidases.
- chemical , pharmacokinetics : Antiviral Agents.
- chemical , pharmacology : Antiviral Agents.
- drug effects : SARS-CoV-2, Viral Load.
- drug therapy : COVID-19.
- metabolism : Lung.
- Humans, Pandemics, Tissue Distribution.
Abstract
Repurposing of approved antiviral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a promising strategy to treat Coronavirus disease 2019 (COVID-19) patients. Previously we reported our hypothesis that the antiviral drugs with high lung distributions might benefit COVID-19 patients by reducing viral loads. So far, chloroquine, lopinavir, hydroxychloroquine, azithromycin, favipiravir, ribavirin, darunavir, remdesivir, and umifenovir have been tested in COVID-19 clinical trials. Here we validated our hypothesis by comparing the pharmacokinetics profiles of these drugs and their capabilities of reducing viral load in clinical trials. According to bulk RNA and single cell RNA sequencing analysis, we found that high expression of both angiotensin converting enzyme 2 (ACE2) and transmembrane Serine Protease 2 (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 viral replication. Lopinavir/ritonavir might inhibit SARS-CoV-2 in the GI tract according to their distribution profiles. We concluded here that the antiviral drugs should be distributed straight to the lung tissue for reducing viral loads in respiratory tract of COVID-19 patients. Additionally, to better evaluate antiviral effects of drugs that target the intestine, the stool samples should also be collected for viral RNA test in the future.
DOI: 10.1016/j.ejphar.2020.173634
PubMed: 33031797
PubMed Central: PMC7536545
Links to Exploration step
pubmed:33031797Le document en format XML
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Electronic address: lchen@dls.rutgers.edu.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:33031797</idno><idno type="pmid">33031797</idno><idno type="doi">10.1016/j.ejphar.2020.173634</idno><idno type="pmc">PMC7536545</idno><idno type="wicri:Area/Main/Corpus">000A75</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000A75</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Tissue distributions of antiviral drugs affect their capabilities of reducing viral loads in COVID-19 treatment.</title><author><name sortKey="Wang, Yan" sort="Wang, Yan" uniqKey="Wang Y" first="Yan" last="Wang">Yan Wang</name><affiliation><nlm:affiliation>Center for Translation Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China. Electronic address: yan.wang@siat.ac.cn.</nlm:affiliation></affiliation></author><author><name sortKey="Chen, Lei" sort="Chen, Lei" uniqKey="Chen L" first="Lei" last="Chen">Lei Chen</name><affiliation><nlm:affiliation>Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, 08854, USA. Electronic address: lchen@dls.rutgers.edu.</nlm:affiliation></affiliation></author></analytic><series><title level="j">European journal of pharmacology</title><idno type="eISSN">1879-0712</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Angiotensin-Converting Enzyme 2 (biosynthesis)</term><term>Antiviral Agents (pharmacokinetics)</term><term>Antiviral Agents (pharmacology)</term><term>COVID-19 (drug therapy)</term><term>Humans (MeSH)</term><term>Lung (metabolism)</term><term>Pandemics (MeSH)</term><term>SARS-CoV-2 (drug effects)</term><term>Serine Endopeptidases (biosynthesis)</term><term>Tissue Distribution (MeSH)</term><term>Viral Load (drug effects)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Angiotensin-Converting Enzyme 2</term><term>Serine Endopeptidases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS-CoV-2</term><term>Viral Load</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Pandemics</term><term>Tissue Distribution</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Repurposing of approved antiviral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a promising strategy to treat Coronavirus disease 2019 (COVID-19) patients. Previously we reported our hypothesis that the antiviral drugs with high lung distributions might benefit COVID-19 patients by reducing viral loads. So far, chloroquine, lopinavir, hydroxychloroquine, azithromycin, favipiravir, ribavirin, darunavir, remdesivir, and umifenovir have been tested in COVID-19 clinical trials. Here we validated our hypothesis by comparing the pharmacokinetics profiles of these drugs and their capabilities of reducing viral load in clinical trials. According to bulk RNA and single cell RNA sequencing analysis, we found that high expression of both angiotensin converting enzyme 2 (ACE2) and transmembrane Serine Protease 2 (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 viral replication. Lopinavir/ritonavir might inhibit SARS-CoV-2 in the GI tract according to their distribution profiles. We concluded here that the antiviral drugs should be distributed straight to the lung tissue for reducing viral loads in respiratory tract of COVID-19 patients. Additionally, to better evaluate antiviral effects of drugs that target the intestine, the stool samples should also be collected for viral RNA test in the future.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33031797</PMID><DateCompleted><Year>2020</Year><Month>12</Month><Day>21</Day></DateCompleted><DateRevised><Year>2020</Year><Month>12</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1879-0712</ISSN><JournalIssue CitedMedium="Internet"><Volume>889</Volume><PubDate><Year>2020</Year><Month>Dec</Month><Day>15</Day></PubDate></JournalIssue><Title>European journal of pharmacology</Title><ISOAbbreviation>Eur J Pharmacol</ISOAbbreviation></Journal><ArticleTitle>Tissue distributions of antiviral drugs affect their capabilities of reducing viral loads in COVID-19 treatment.</ArticleTitle><Pagination><MedlinePgn>173634</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0014-2999(20)30726-3</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ejphar.2020.173634</ELocationID><Abstract><AbstractText>Repurposing of approved antiviral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a promising strategy to treat Coronavirus disease 2019 (COVID-19) patients. Previously we reported our hypothesis that the antiviral drugs with high lung distributions might benefit COVID-19 patients by reducing viral loads. So far, chloroquine, lopinavir, hydroxychloroquine, azithromycin, favipiravir, ribavirin, darunavir, remdesivir, and umifenovir have been tested in COVID-19 clinical trials. Here we validated our hypothesis by comparing the pharmacokinetics profiles of these drugs and their capabilities of reducing viral load in clinical trials. According to bulk RNA and single cell RNA sequencing analysis, we found that high expression of both angiotensin converting enzyme 2 (ACE2) and transmembrane Serine Protease 2 (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 viral replication. Lopinavir/ritonavir might inhibit SARS-CoV-2 in the GI tract according to their distribution profiles. We concluded here that the antiviral drugs should be distributed straight to the lung tissue for reducing viral loads in respiratory tract of COVID-19 patients. Additionally, to better evaluate antiviral effects of drugs that target the intestine, the stool samples should also be collected for viral RNA test in the future.</AbstractText><CopyrightInformation>Copyright © 2020 Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Center for Translation Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China. Electronic address: yan.wang@siat.ac.cn.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Lei</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, 08854, USA. 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