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HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus

Identifieur interne : 005332 ( Main/Exploration ); précédent : 005331; suivant : 005333

HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus

Auteurs : Norio Yamamoto [Japon] ; Rongge Yang [Japon] ; Yoshiyuki Yoshinaka [Japon] ; Shinji Amari [Japon] ; Tatsuya Nakano [Japon] ; Jindrich Cinatl [Allemagne] ; Holger Rabenau [Allemagne] ; Hans Wilhelm Doerr [Allemagne] ; Gerhard Hunsmann [Allemagne] ; Akira Otaka [Japon] ; Hirokazu Tamamura [Japon] ; Nobutaka Fujii [Japon] ; Naoki Yamamoto [Japon]

Source :

RBID : PMC:7111005

Descripteurs français

English descriptors

Abstract

A novel coronavirus has been identified as an etiological agent of severe acute respiratory syndrome (SARS). To rapidly identify anti-SARS drugs available for clinical use, we screened a set of compounds that included antiviral drugs already in wide use. Here we report that the HIV-1 protease inhibitor, nelfinavir, strongly inhibited replication of the SARS coronavirus (SARS-CoV). Nelfinavir inhibited the cytopathic effect induced by SARS-CoV infection. Expression of viral antigens was much lower in infected cells treated with nelfinavir than in untreated infected cells. Quantitative RT-PCR analysis showed that nelfinavir could decrease the production of virions from Vero cells. Experiments with various timings of drug addition revealed that nelfinavir exerted its effect not at the entry step, but at the post-entry step of SARS-CoV infection. Our results suggest that nelfinavir should be examined clinically for the treatment of SARS and has potential as a good lead compound for designing anti-SARS drugs.


Url:
DOI: 10.1016/j.bbrc.2004.04.083
PubMed: 15144898
PubMed Central: 7111005


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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<profileDesc>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Animals</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Chlorocebus aethiops</term>
<term>Fluorescent Antibody Technique</term>
<term>HIV Protease Inhibitors (pharmacology)</term>
<term>Lethal Dose 50</term>
<term>Nelfinavir (pharmacology)</term>
<term>RNA, Viral (analysis)</term>
<term>Ritonavir (pharmacology)</term>
<term>SARS Virus (drug effects)</term>
<term>SARS Virus (pathogenicity)</term>
<term>SARS Virus (physiology)</term>
<term>Time Factors</term>
<term>Vero Cells</term>
<term>Virus Replication (drug effects)</term>
</keywords>
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<term>ARN viral (analyse)</term>
<term>Animaux</term>
<term>Antiviraux (pharmacologie)</term>
<term>Cellules Vero</term>
<term>Dose létale 50</term>
<term>Facteurs temps</term>
<term>Inhibiteurs de protéase du VIH (pharmacologie)</term>
<term>Nelfinavir (pharmacologie)</term>
<term>Ritonavir (pharmacologie)</term>
<term>Réplication virale ()</term>
<term>Technique d'immunofluorescence</term>
<term>Virus du SRAS ()</term>
<term>Virus du SRAS (pathogénicité)</term>
<term>Virus du SRAS (physiologie)</term>
</keywords>
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<term>RNA, Viral</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Antiviral Agents</term>
<term>HIV Protease Inhibitors</term>
<term>Nelfinavir</term>
<term>Ritonavir</term>
</keywords>
<keywords scheme="MESH" qualifier="analyse" xml:lang="fr">
<term>ARN viral</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>SARS Virus</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en">
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr">
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr">
<term>Antiviraux</term>
<term>Inhibiteurs de protéase du VIH</term>
<term>Nelfinavir</term>
<term>Ritonavir</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr">
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en">
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Chlorocebus aethiops</term>
<term>Fluorescent Antibody Technique</term>
<term>Lethal Dose 50</term>
<term>Time Factors</term>
<term>Vero Cells</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Cellules Vero</term>
<term>Dose létale 50</term>
<term>Facteurs temps</term>
<term>Réplication virale</term>
<term>Technique d'immunofluorescence</term>
<term>Virus du SRAS</term>
</keywords>
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</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>A novel coronavirus has been identified as an etiological agent of severe acute respiratory syndrome (SARS). To rapidly identify anti-SARS drugs available for clinical use, we screened a set of compounds that included antiviral drugs already in wide use. Here we report that the HIV-1 protease inhibitor, nelfinavir, strongly inhibited replication of the SARS coronavirus (SARS-CoV). Nelfinavir inhibited the cytopathic effect induced by SARS-CoV infection. Expression of viral antigens was much lower in infected cells treated with nelfinavir than in untreated infected cells. Quantitative RT-PCR analysis showed that nelfinavir could decrease the production of virions from Vero cells. Experiments with various timings of drug addition revealed that nelfinavir exerted its effect not at the entry step, but at the post-entry step of SARS-CoV infection. Our results suggest that nelfinavir should be examined clinically for the treatment of SARS and has potential as a good lead compound for designing anti-SARS drugs.</p>
</div>
</front>
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<country name="Japon">
<region name="Région de Kantō">
<name sortKey="Yamamoto, Norio" sort="Yamamoto, Norio" uniqKey="Yamamoto N" first="Norio" last="Yamamoto">Norio Yamamoto</name>
</region>
<name sortKey="Amari, Shinji" sort="Amari, Shinji" uniqKey="Amari S" first="Shinji" last="Amari">Shinji Amari</name>
<name sortKey="Fujii, Nobutaka" sort="Fujii, Nobutaka" uniqKey="Fujii N" first="Nobutaka" last="Fujii">Nobutaka Fujii</name>
<name sortKey="Nakano, Tatsuya" sort="Nakano, Tatsuya" uniqKey="Nakano T" first="Tatsuya" last="Nakano">Tatsuya Nakano</name>
<name sortKey="Otaka, Akira" sort="Otaka, Akira" uniqKey="Otaka A" first="Akira" last="Otaka">Akira Otaka</name>
<name sortKey="Tamamura, Hirokazu" sort="Tamamura, Hirokazu" uniqKey="Tamamura H" first="Hirokazu" last="Tamamura">Hirokazu Tamamura</name>
<name sortKey="Yamamoto, Naoki" sort="Yamamoto, Naoki" uniqKey="Yamamoto N" first="Naoki" last="Yamamoto">Naoki Yamamoto</name>
<name sortKey="Yang, Rongge" sort="Yang, Rongge" uniqKey="Yang R" first="Rongge" last="Yang">Rongge Yang</name>
<name sortKey="Yoshinaka, Yoshiyuki" sort="Yoshinaka, Yoshiyuki" uniqKey="Yoshinaka Y" first="Yoshiyuki" last="Yoshinaka">Yoshiyuki Yoshinaka</name>
</country>
<country name="Allemagne">
<region name="Hesse (Land)">
<name sortKey="Cinatl, Jindrich" sort="Cinatl, Jindrich" uniqKey="Cinatl J" first="Jindrich" last="Cinatl">Jindrich Cinatl</name>
</region>
<name sortKey="Doerr, Hans Wilhelm" sort="Doerr, Hans Wilhelm" uniqKey="Doerr H" first="Hans Wilhelm" last="Doerr">Hans Wilhelm Doerr</name>
<name sortKey="Hunsmann, Gerhard" sort="Hunsmann, Gerhard" uniqKey="Hunsmann G" first="Gerhard" last="Hunsmann">Gerhard Hunsmann</name>
<name sortKey="Rabenau, Holger" sort="Rabenau, Holger" uniqKey="Rabenau H" first="Holger" last="Rabenau">Holger Rabenau</name>
</country>
</tree>
</affiliations>
</record>

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