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• W2076911722 startingPage "8017" @default.
• W2076911722 abstract "ABSTRACT Severe acute respiratory syndrome (SARS) is an infectious and highly contagious disease that is caused by SARS coronavirus (SARS-CoV) and for which there are currently no approved treatments. We report the discovery and characterization of small-molecule inhibitors of SARS-CoV replication that block viral entry by three different mechanisms. The compounds were discovered by screening a chemical library of compounds for blocking of entry of HIV-1 pseudotyped with SARS-CoV surface glycoprotein S (SARS-S) but not that of HIV-1 pseudotyped with vesicular stomatitis virus surface glycoprotein G (VSV-G). Studies on their mechanisms of action revealed that the compounds act by three distinct mechanisms: (i) SSAA09E2 { N -[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1,2-oxazole-5-carboxamide} acts through a novel mechanism of action, by blocking early interactions of SARS-S with the receptor for SARS-CoV, angiotensin converting enzyme 2 (ACE2); (ii) SSAA09E1 {[( Z )-1-thiophen-2-ylethylideneamino]thiourea} acts later, by blocking cathepsin L, a host protease required for processing of SARS-S during viral entry; and (iii) SSAA09E3 [ N -(9,10-dioxo-9,10-dihydroanthracen-2-yl)benzamide] also acts later and does not affect interactions of SARS-S with ACE2 or the enzymatic functions of cathepsin L but prevents fusion of the viral membrane with the host cellular membrane. Our work demonstrates that there are at least three independent strategies for blocking SARS-CoV entry, validates these mechanisms of inhibition, and introduces promising leads for the development of SARS therapeutics." @default.
• W2076911722 created "2016-06-24" @default.
• W2076911722 creator A5015640501 @default.
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• W2076911722 creator A5049782797 @default.
• W2076911722 creator A5078734256 @default.
• W2076911722 creator A5087515662 @default.
• W2076911722 date "2013-07-15" @default.
• W2076911722 modified "2023-10-14" @default.
• W2076911722 title "Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus Entry That Act by Three Distinct Mechanisms" @default.
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• W2076911722 doi "https://doi.org/10.1128/jvi.00998-13" @default.
• W2076911722 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3700180" @default.
• W2076911722 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23678171" @default.
• W2076911722 hasPublicationYear "2013" @default.
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