SrasV1, PascalFrancis, Checkpoint, bibRecord, 000823

Inhibition of severe acute respiratory syndrome-associated coronavirus (SARSCoV) by calpain inhibitors and β-D-N4-hydroxycytidine

Identifieur interne : 000823 ( PascalFrancis/Checkpoint ); précédent : 000822; suivant : 000824

Inhibition of severe acute respiratory syndrome-associated coronavirus (SARSCoV) by calpain inhibitors and β-D-N4-hydroxycytidine

Auteurs : Dale L. Barnard [États-Unis] ; Valerie D. Hubbard [États-Unis] ; Jared Burton [États-Unis] ; Donald F. Smee [États-Unis] ; John D. Morrey [États-Unis] ; Michael J. Otto [États-Unis] ; Robert W. Sidwell [États-Unis]

Source :

Antiviral chemistry & chemotherapy [ 0956-3202 ] ; 2004.

RBID : Pascal:05-0190006

Descripteurs français

Pascal (Inist)
- Antiviral, In vitro, Coronavirus, Inhibiteur enzyme, Calpain, Cytidine, Guanosine, Adénosine, Analogue nucléoside, Relation structure activité, Recherche développement, Syndrome respiratoire aigu sévère.

English descriptors

KwdEn :
- Adenosine, Antiviral, Calpain, Coronavirus, Cytidine, Enzyme inhibitor, Guanosine, In vitro, Nucleoside analog, Research and development, Severe acute respiratory syndrome, Structure activity relation.

Abstract

We evaluated two types of compounds for efficacy in inhibiting SARSCoV replication in vitro: calpain inhibitors (a class of cellular cysteine proteinases) and a number of nucleoside analogues. Cytopathic effect reduction assays visually determined with spectrophotometric verification by neutral red (NR) uptake assay were used to evaluate cytotoxicity and antiviral potency of the compounds. Significantly inhibitory compounds were then evaluated in virus yield reduction assays. Two calpain inhibitors, Val-Leu-CHO (calpain inhibitor VI) and Z-Val-Phe-Ala-CHO (calpain inhibitor III), were the most potent inhibitors of SARSCoV. By virus yield reduction assay, calpain inhibitor VI had a 90% effective concentration (EC₉₀) of 3 μM and calpain inhibitor III had an EC₉₀ of 15 μM. β-D-N⁴-hydroxycytidine was the most selective nucleoside analogue inhibitor with an EC₉₀ of 6 μM by virus yield reduction assay. These compounds or analogues warrant further evaluation as potential therapies for treating SARS or could be used as lead compounds for discovery of more potent SARSCoV inhibitors.

Affiliations:

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Pascal:05-0190006

Le document en format XML

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<front><div type="abstract" xml:lang="en">We evaluated two types of compounds for efficacy in inhibiting SARSCoV replication in vitro: calpain inhibitors (a class of cellular cysteine proteinases) and a number of nucleoside analogues. Cytopathic effect reduction assays visually determined with spectrophotometric verification by neutral red (NR) uptake assay were used to evaluate cytotoxicity and antiviral potency of the compounds. Significantly inhibitory compounds were then evaluated in virus yield reduction assays. Two calpain inhibitors, Val-Leu-CHO (calpain inhibitor VI) and Z-Val-Phe-Ala-CHO (calpain inhibitor III), were the most potent inhibitors of SARSCoV. By virus yield reduction assay, calpain inhibitor VI had a 90% effective concentration (EC<sub>90</sub>
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 of 15 μM. β-D-N<sup>4</sup>
-hydroxycytidine was the most selective nucleoside analogue inhibitor with an EC<sub>90</sub>
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<fC03 i1="11" i2="X" l="FRE"><s0>Recherche développement</s0>
<s5>19</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>Research and development</s0>
<s5>19</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>Investigación desarrollo</s0>
<s5>19</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE"><s0>Syndrome respiratoire aigu sévère</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG"><s0>Severe acute respiratory syndrome</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC03 i1="12" i2="X" l="SPA"><s0>Síndrome respiratorio agudo severo</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Cysteine endopeptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Cysteine endopeptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Cysteine endopeptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Peptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Peptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Peptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Hydrolases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Hydrolases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Hydrolases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Enzima</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="08" i2="X" l="FRE"><s0>Appareil respiratoire pathologie</s0>
<s5>61</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>Respiratory disease</s0>
<s5>61</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA"><s0>Aparato respiratorio patología</s0>
<s5>61</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE"><s0>Poumon pathologie</s0>
<s5>62</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG"><s0>Lung disease</s0>
<s5>62</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA"><s0>Pulmón patología</s0>
<s5>62</s5>
</fC07>
<fC07 i1="10" i2="X" l="FRE"><s0>Virose</s0>
<s5>63</s5>
</fC07>
<fC07 i1="10" i2="X" l="ENG"><s0>Viral disease</s0>
<s5>63</s5>
</fC07>
<fC07 i1="10" i2="X" l="SPA"><s0>Virosis</s0>
<s5>63</s5>
</fC07>
<fC07 i1="11" i2="X" l="FRE"><s0>Infection</s0>
</fC07>
<fC07 i1="11" i2="X" l="ENG"><s0>Infection</s0>
</fC07>
<fC07 i1="11" i2="X" l="SPA"><s0>Infección</s0>
</fC07>
<fN21><s1>129</s1>
</fN21>
<fN44 i1="01"><s1>PSI</s1>
</fN44>
<fN82><s1>PSI</s1>
</fN82>
</pA>
</standard>
</inist>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Utah</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Utah"><name sortKey="Barnard, Dale L" sort="Barnard, Dale L" uniqKey="Barnard D" first="Dale L." last="Barnard">Dale L. Barnard</name>
</region>
<name sortKey="Burton, Jared" sort="Burton, Jared" uniqKey="Burton J" first="Jared" last="Burton">Jared Burton</name>
<name sortKey="Hubbard, Valerie D" sort="Hubbard, Valerie D" uniqKey="Hubbard V" first="Valerie D." last="Hubbard">Valerie D. Hubbard</name>
<name sortKey="Morrey, John D" sort="Morrey, John D" uniqKey="Morrey J" first="John D." last="Morrey">John D. Morrey</name>
<name sortKey="Otto, Michael J" sort="Otto, Michael J" uniqKey="Otto M" first="Michael J." last="Otto">Michael J. Otto</name>
<name sortKey="Sidwell, Robert W" sort="Sidwell, Robert W" uniqKey="Sidwell R" first="Robert W." last="Sidwell">Robert W. Sidwell</name>
<name sortKey="Smee, Donald F" sort="Smee, Donald F" uniqKey="Smee D" first="Donald F." last="Smee">Donald F. Smee</name>
</country>
</tree>
</affiliations>
</record>

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   |texte=   Inhibition of severe acute respiratory syndrome-associated coronavirus (SARSCoV) by calpain inhibitors and β-D-N4-hydroxycytidine
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Inhibition of severe acute respiratory syndrome-associated coronavirus (SARSCoV) by calpain inhibitors and β-D-N4-hydroxycytidine

Inhibition of severe acute respiratory syndrome-associated coronavirus (SARSCoV) by calpain inhibitors and β-D-N4-hydroxycytidine

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