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Simultaneous Treatment of Human Bronchial Epithelial Cells with Serine and Cysteine Protease Inhibitors Prevents Severe Acute Respiratory Syndrome Coronavirus Entry

Identifieur interne : 000035 ( PascalFrancis/Checkpoint ); précédent : 000034; suivant : 000036

Simultaneous Treatment of Human Bronchial Epithelial Cells with Serine and Cysteine Protease Inhibitors Prevents Severe Acute Respiratory Syndrome Coronavirus Entry

Auteurs : Miyuki Kawase [Japon] ; Kazuya Shirato [Japon] ; Lia Van Der Hoek [Pays-Bas] ; Fumihiro Taguchi [Japon] ; Shutoku Matsuyama [Japon]

Source :

RBID : Pascal:12-0269207

Descripteurs français

English descriptors

Abstract

The type II transmembrane protease TMPRSS2 activates the spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) on the cell surface following receptor binding during viral entry into cells. In the absence of TMPRSS2, SARS-CoV achieves cell entry via an endosomal pathway in which cathepsin L may play an important role, i.e., the activation of spike protein fusogenicity. This study shows that a commercial serine protease inhibitor (camostat) partially blocked infection by SARS-CoV and human coronavirus NL63 (HCoV-NL63) in HeLa cells expressing the receptor angiotensin-converting enzyme 2 (ACE2) and TMPRSS2. Simultaneous treatment of the cells with camostat and EST [(23,25)trans-epoarysuccinyl-L-leurylamindo-3-methylbutane ethyl ester], a cathepsin inhibitor, efficiently prevented both cell entry and the multistep growth of SARS-CoV in human Calu-3 airway epithelial cells. This efficient inhibition could be attributed to the dual blockade of entry from the cell surface and through the endosomal pathway. These observations suggest camostat as a candidate antiviral drug to prevent or depress TMPRSS2-dependent infection by SARS-CoV.


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Pascal:12-0269207

Le document en format XML

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<div type="abstract" xml:lang="en">The type II transmembrane protease TMPRSS2 activates the spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) on the cell surface following receptor binding during viral entry into cells. In the absence of TMPRSS2, SARS-CoV achieves cell entry via an endosomal pathway in which cathepsin L may play an important role, i.e., the activation of spike protein fusogenicity. This study shows that a commercial serine protease inhibitor (camostat) partially blocked infection by SARS-CoV and human coronavirus NL63 (HCoV-NL63) in HeLa cells expressing the receptor angiotensin-converting enzyme 2 (ACE2) and TMPRSS2. Simultaneous treatment of the cells with camostat and EST [(23,25)trans-epoarysuccinyl-L-leurylamindo-3-methylbutane ethyl ester], a cathepsin inhibitor, efficiently prevented both cell entry and the multistep growth of SARS-CoV in human Calu-3 airway epithelial cells. This efficient inhibition could be attributed to the dual blockade of entry from the cell surface and through the endosomal pathway. These observations suggest camostat as a candidate antiviral drug to prevent or depress TMPRSS2-dependent infection by SARS-CoV.</div>
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<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="SPA">
<s0>Enzima</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="07" i2="X" l="FRE">
<s0>Virose</s0>
</fC07>
<fC07 i1="07" i2="X" l="ENG">
<s0>Viral disease</s0>
</fC07>
<fC07 i1="07" i2="X" l="SPA">
<s0>Virosis</s0>
</fC07>
<fC07 i1="08" i2="X" l="FRE">
<s0>Infection</s0>
</fC07>
<fC07 i1="08" i2="X" l="ENG">
<s0>Infection</s0>
</fC07>
<fC07 i1="08" i2="X" l="SPA">
<s0>Infección</s0>
</fC07>
<fC07 i1="09" i2="X" l="FRE">
<s0>Pathologie de l'appareil respiratoire</s0>
<s5>13</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG">
<s0>Respiratory disease</s0>
<s5>13</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA">
<s0>Aparato respiratorio patología</s0>
<s5>13</s5>
</fC07>
<fC07 i1="10" i2="X" l="FRE">
<s0>Pathologie des poumons</s0>
<s5>16</s5>
</fC07>
<fC07 i1="10" i2="X" l="ENG">
<s0>Lung disease</s0>
<s5>16</s5>
</fC07>
<fC07 i1="10" i2="X" l="SPA">
<s0>Pulmón patología</s0>
<s5>16</s5>
</fC07>
<fN21>
<s1>205</s1>
</fN21>
<fN44 i1="01">
<s1>OTO</s1>
</fN44>
<fN82>
<s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
<affiliations>
<list>
<country>
<li>Japon</li>
<li>Pays-Bas</li>
</country>
<region>
<li>Hollande-Septentrionale</li>
<li>Région de Kantō</li>
</region>
<settlement>
<li>Amsterdam</li>
<li>Tokyo</li>
</settlement>
<orgName>
<li>Université d'Amsterdam</li>
</orgName>
</list>
<tree>
<country name="Japon">
<region name="Région de Kantō">
<name sortKey="Kawase, Miyuki" sort="Kawase, Miyuki" uniqKey="Kawase M" first="Miyuki" last="Kawase">Miyuki Kawase</name>
</region>
<name sortKey="Matsuyama, Shutoku" sort="Matsuyama, Shutoku" uniqKey="Matsuyama S" first="Shutoku" last="Matsuyama">Shutoku Matsuyama</name>
<name sortKey="Shirato, Kazuya" sort="Shirato, Kazuya" uniqKey="Shirato K" first="Kazuya" last="Shirato">Kazuya Shirato</name>
<name sortKey="Taguchi, Fumihiro" sort="Taguchi, Fumihiro" uniqKey="Taguchi F" first="Fumihiro" last="Taguchi">Fumihiro Taguchi</name>
</country>
<country name="Pays-Bas">
<region name="Hollande-Septentrionale">
<name sortKey="Der Hoek, Lia Van" sort="Der Hoek, Lia Van" uniqKey="Der Hoek L" first="Lia Van" last="Der Hoek">Lia Van Der Hoek</name>
</region>
</country>
</tree>
</affiliations>
</record>

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