The SARS-CoV-2 cytopathic effect is blocked with autophagy modulators.
Identifieur interne : 001467 ( Main/Corpus ); précédent : 001466; suivant : 001468The SARS-CoV-2 cytopathic effect is blocked with autophagy modulators.
Auteurs : Kirill Gorshkov ; Catherine Z. Chen ; Robert Bostwick ; Lynn Rasmussen ; Miao Xu ; Manisha Pradhan ; Bruce Nguyen Tran ; Wei Zhu ; Khalida Shamim ; Wenwei Huang ; Xin Hu ; Min Shen ; Carleen Klumpp-Thomas ; Zina Itkin ; Paul Shinn ; Anton Simeonov ; Sam Michael ; Matthew D. Hall ; Donald C. Lo ; Wei ZhengSource :
- bioRxiv : the preprint server for biology ; 2020.
Abstract
SARS-CoV-02 is a new type of coronavirus capable of rapid transmission and causing severe clinical symptoms; much of which has unknown biological etiology. It has prompted researchers to rapidly mobilize their efforts towards identifying and developing anti-viral therapeutics and vaccines. Discovering and understanding the virus' pathways of infection, host-protein interactions, and cytopathic effects will greatly aid in the design of new therapeutics to treat COVID-19. While it is known that chloroquine and hydroxychloroquine, extensively explored as clinical agents for COVID-19, have multiple cellular effects including inhibiting autophagy, there are also dose-limiting toxicities in patients that make clearly establishing their potential mechanisms-of-action problematic. Therefore, we evaluated a range of other autophagy modulators to identify an alternative autophagy-based drug repurposing opportunity. In this work, we found that 6 of these compounds blocked the cytopathic effect of SARS-CoV-2 in Vero-E6 cells with EC50 values ranging from 2.0 to 13 μM and selectivity indices ranging from 1.5 to >10-fold. Immunofluorescence staining for LC3B and LysoTracker dye staining assays in several cell lines indicated their potency and efficacy for inhibiting autophagy correlated with the measurements in the SARS-CoV-2 cytopathic effect assay. Our data suggest that autophagy pathways could be targeted to combat SARS-CoV-2 infections and become an important component of drug combination therapies to improve the treatment outcomes for COVID-19.
DOI: 10.1101/2020.05.16.091520
PubMed: 32511355
PubMed Central: PMC7259466
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Chen</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Bostwick, Robert" sort="Bostwick, Robert" uniqKey="Bostwick R" first="Robert" last="Bostwick">Robert Bostwick</name><affiliation><nlm:affiliation>Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama, 35205.</nlm:affiliation></affiliation></author><author><name sortKey="Rasmussen, Lynn" sort="Rasmussen, Lynn" uniqKey="Rasmussen L" first="Lynn" last="Rasmussen">Lynn Rasmussen</name><affiliation><nlm:affiliation>Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama, 35205.</nlm:affiliation></affiliation></author><author><name sortKey="Xu, Miao" sort="Xu, Miao" uniqKey="Xu M" first="Miao" last="Xu">Miao Xu</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Pradhan, Manisha" sort="Pradhan, Manisha" uniqKey="Pradhan M" first="Manisha" last="Pradhan">Manisha Pradhan</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Tran, Bruce Nguyen" sort="Tran, Bruce Nguyen" uniqKey="Tran B" first="Bruce Nguyen" last="Tran">Bruce Nguyen Tran</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Zhu, Wei" sort="Zhu, Wei" uniqKey="Zhu W" first="Wei" last="Zhu">Wei Zhu</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Shamim, Khalida" sort="Shamim, Khalida" uniqKey="Shamim K" first="Khalida" last="Shamim">Khalida Shamim</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Huang, Wenwei" sort="Huang, Wenwei" uniqKey="Huang W" first="Wenwei" last="Huang">Wenwei Huang</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Hu, Xin" sort="Hu, Xin" uniqKey="Hu X" first="Xin" last="Hu">Xin Hu</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Shen, Min" sort="Shen, Min" uniqKey="Shen M" first="Min" last="Shen">Min Shen</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Klumpp Thomas, Carleen" sort="Klumpp Thomas, Carleen" uniqKey="Klumpp Thomas C" first="Carleen" last="Klumpp-Thomas">Carleen Klumpp-Thomas</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Itkin, Zina" sort="Itkin, Zina" uniqKey="Itkin Z" first="Zina" last="Itkin">Zina Itkin</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Shinn, Paul" sort="Shinn, Paul" uniqKey="Shinn P" first="Paul" last="Shinn">Paul Shinn</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Simeonov, Anton" sort="Simeonov, Anton" uniqKey="Simeonov A" first="Anton" last="Simeonov">Anton Simeonov</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Michael, Sam" sort="Michael, Sam" uniqKey="Michael S" first="Sam" last="Michael">Sam Michael</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Hall, Matthew D" sort="Hall, Matthew D" uniqKey="Hall M" first="Matthew D" last="Hall">Matthew D. Hall</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Lo, Donald C" sort="Lo, Donald C" uniqKey="Lo D" first="Donald C" last="Lo">Donald C. Lo</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Zheng, Wei" sort="Zheng, Wei" uniqKey="Zheng W" first="Wei" last="Zheng">Wei Zheng</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32511355</idno><idno type="pmid">32511355</idno><idno type="doi">10.1101/2020.05.16.091520</idno><idno type="pmc">PMC7259466</idno><idno type="wicri:Area/Main/Corpus">001467</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001467</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The SARS-CoV-2 cytopathic effect is blocked with autophagy modulators.</title><author><name sortKey="Gorshkov, Kirill" sort="Gorshkov, Kirill" uniqKey="Gorshkov K" first="Kirill" last="Gorshkov">Kirill Gorshkov</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Chen, Catherine Z" sort="Chen, Catherine Z" uniqKey="Chen C" first="Catherine Z" last="Chen">Catherine Z. Chen</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Bostwick, Robert" sort="Bostwick, Robert" uniqKey="Bostwick R" first="Robert" last="Bostwick">Robert Bostwick</name><affiliation><nlm:affiliation>Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama, 35205.</nlm:affiliation></affiliation></author><author><name sortKey="Rasmussen, Lynn" sort="Rasmussen, Lynn" uniqKey="Rasmussen L" first="Lynn" last="Rasmussen">Lynn Rasmussen</name><affiliation><nlm:affiliation>Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama, 35205.</nlm:affiliation></affiliation></author><author><name sortKey="Xu, Miao" sort="Xu, Miao" uniqKey="Xu M" first="Miao" last="Xu">Miao Xu</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Pradhan, Manisha" sort="Pradhan, Manisha" uniqKey="Pradhan M" first="Manisha" last="Pradhan">Manisha Pradhan</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Tran, Bruce Nguyen" sort="Tran, Bruce Nguyen" uniqKey="Tran B" first="Bruce Nguyen" last="Tran">Bruce Nguyen Tran</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Zhu, Wei" sort="Zhu, Wei" uniqKey="Zhu W" first="Wei" last="Zhu">Wei Zhu</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Shamim, Khalida" sort="Shamim, Khalida" uniqKey="Shamim K" first="Khalida" last="Shamim">Khalida Shamim</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Huang, Wenwei" sort="Huang, Wenwei" uniqKey="Huang W" first="Wenwei" last="Huang">Wenwei Huang</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Hu, Xin" sort="Hu, Xin" uniqKey="Hu X" first="Xin" last="Hu">Xin Hu</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Shen, Min" sort="Shen, Min" uniqKey="Shen M" first="Min" last="Shen">Min Shen</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Klumpp Thomas, Carleen" sort="Klumpp Thomas, Carleen" uniqKey="Klumpp Thomas C" first="Carleen" last="Klumpp-Thomas">Carleen Klumpp-Thomas</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Itkin, Zina" sort="Itkin, Zina" uniqKey="Itkin Z" first="Zina" last="Itkin">Zina Itkin</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Shinn, Paul" sort="Shinn, Paul" uniqKey="Shinn P" first="Paul" last="Shinn">Paul Shinn</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Simeonov, Anton" sort="Simeonov, Anton" uniqKey="Simeonov A" first="Anton" last="Simeonov">Anton Simeonov</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Michael, Sam" sort="Michael, Sam" uniqKey="Michael S" first="Sam" last="Michael">Sam Michael</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Hall, Matthew D" sort="Hall, Matthew D" uniqKey="Hall M" first="Matthew D" last="Hall">Matthew D. Hall</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Lo, Donald C" sort="Lo, Donald C" uniqKey="Lo D" first="Donald C" last="Lo">Donald C. Lo</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author><author><name sortKey="Zheng, Wei" sort="Zheng, Wei" uniqKey="Zheng W" first="Wei" last="Zheng">Wei Zheng</name><affiliation><nlm:affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</nlm:affiliation></affiliation></author></analytic><series><title level="j">bioRxiv : the preprint server for biology</title><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">SARS-CoV-02 is a new type of coronavirus capable of rapid transmission and causing severe clinical symptoms; much of which has unknown biological etiology. It has prompted researchers to rapidly mobilize their efforts towards identifying and developing anti-viral therapeutics and vaccines. Discovering and understanding the virus' pathways of infection, host-protein interactions, and cytopathic effects will greatly aid in the design of new therapeutics to treat COVID-19. While it is known that chloroquine and hydroxychloroquine, extensively explored as clinical agents for COVID-19, have multiple cellular effects including inhibiting autophagy, there are also dose-limiting toxicities in patients that make clearly establishing their potential mechanisms-of-action problematic. Therefore, we evaluated a range of other autophagy modulators to identify an alternative autophagy-based drug repurposing opportunity. In this work, we found that 6 of these compounds blocked the cytopathic effect of SARS-CoV-2 in Vero-E6 cells with EC<sub>50</sub> values ranging from 2.0 to 13 μM and selectivity indices ranging from 1.5 to >10-fold. Immunofluorescence staining for LC3B and LysoTracker dye staining assays in several cell lines indicated their potency and efficacy for inhibiting autophagy correlated with the measurements in the SARS-CoV-2 cytopathic effect assay. Our data suggest that autophagy pathways could be targeted to combat SARS-CoV-2 infections and become an important component of drug combination therapies to improve the treatment outcomes for COVID-19.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">32511355</PMID><DateRevised><Year>2021</Year><Month>01</Month><Day>10</Day></DateRevised><Article PubModel="Electronic"><Journal><JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year><Month>May</Month><Day>28</Day></PubDate></JournalIssue><Title>bioRxiv : the preprint server for biology</Title><ISOAbbreviation>bioRxiv</ISOAbbreviation></Journal><ArticleTitle>The SARS-CoV-2 cytopathic effect is blocked with autophagy modulators.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">2020.05.16.091520</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1101/2020.05.16.091520</ELocationID><Abstract><AbstractText>SARS-CoV-02 is a new type of coronavirus capable of rapid transmission and causing severe clinical symptoms; much of which has unknown biological etiology. It has prompted researchers to rapidly mobilize their efforts towards identifying and developing anti-viral therapeutics and vaccines. Discovering and understanding the virus' pathways of infection, host-protein interactions, and cytopathic effects will greatly aid in the design of new therapeutics to treat COVID-19. While it is known that chloroquine and hydroxychloroquine, extensively explored as clinical agents for COVID-19, have multiple cellular effects including inhibiting autophagy, there are also dose-limiting toxicities in patients that make clearly establishing their potential mechanisms-of-action problematic. Therefore, we evaluated a range of other autophagy modulators to identify an alternative autophagy-based drug repurposing opportunity. In this work, we found that 6 of these compounds blocked the cytopathic effect of SARS-CoV-2 in Vero-E6 cells with EC<sub>50</sub> values ranging from 2.0 to 13 μM and selectivity indices ranging from 1.5 to >10-fold. Immunofluorescence staining for LC3B and LysoTracker dye staining assays in several cell lines indicated their potency and efficacy for inhibiting autophagy correlated with the measurements in the SARS-CoV-2 cytopathic effect assay. Our data suggest that autophagy pathways could be targeted to combat SARS-CoV-2 infections and become an important component of drug combination therapies to improve the treatment outcomes for COVID-19.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gorshkov</LastName><ForeName>Kirill</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Catherine Z</ForeName><Initials>CZ</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bostwick</LastName><ForeName>Robert</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama, 35205.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rasmussen</LastName><ForeName>Lynn</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama, 35205.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Miao</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pradhan</LastName><ForeName>Manisha</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tran</LastName><ForeName>Bruce Nguyen</ForeName><Initials>BN</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Wei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shamim</LastName><ForeName>Khalida</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Wenwei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hu</LastName><ForeName>Xin</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shen</LastName><ForeName>Min</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Klumpp-Thomas</LastName><ForeName>Carleen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Itkin</LastName><ForeName>Zina</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shinn</LastName><ForeName>Paul</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Simeonov</LastName><ForeName>Anton</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Michael</LastName><ForeName>Sam</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hall</LastName><ForeName>Matthew D</ForeName><Initials>MD</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lo</LastName><ForeName>Donald C</ForeName><Initials>DC</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Wei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>National Center for Advancing Translational Sciences, 9800 Medical Center Drive, Rockville, MD, 20850.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D000076942">Preprint</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>05</Month><Day>28</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>bioRxiv</MedlineTA><NlmUniqueID>101680187</NlmUniqueID></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="UpdateIn"><RefSource>ACS Infect Dis. 2020 Dec 21;:</RefSource><PMID Version="1">33346633</PMID></CommentsCorrections></CommentsCorrectionsList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">SARS-CoV-2</Keyword><Keyword MajorTopicYN="N">autophagy</Keyword><Keyword MajorTopicYN="N">coronavirus</Keyword><Keyword MajorTopicYN="N">cytopathic effect</Keyword><Keyword MajorTopicYN="N">small molecule inhibitors</Keyword></KeywordList><CoiStatement>Declaration of interests: The authors report no conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>6</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>6</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>6</Month><Day>9</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32511355</ArticleId><ArticleId IdType="doi">10.1101/2020.05.16.091520</ArticleId><ArticleId IdType="pmc">PMC7259466</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Clin Pharmacokinet. 1996 Oct;31(4):257-74</Citation><ArticleIdList><ArticleId IdType="pubmed">8896943</ArticleId></ArticleIdList></Reference><Reference><Citation>Int J Antimicrob Agents. 2020 May;55(5):105938</Citation><ArticleIdList><ArticleId IdType="pubmed">32171740</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 2003 Nov 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