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Using serpins cysteine protease cross-specificity to possibly trap SARS-CoV-2 Mpro with reactive center loop chimera.
Jairajpuri, Mohamad Aman; Ansari, Shoyab.
  • Jairajpuri MA; Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.
  • Ansari S; Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.
Clin Sci (Lond) ; 134(17): 2235-2241, 2020 09 18.
Artículo en Inglés | MEDLINE | ID: covidwho-738221
ABSTRACT
Human serine protease inhibitors (serpins) are the main inhibitors of serine proteases, but some of them also have the capability to effectively inhibit cysteine proteases. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) main protease (Mpro) is a chymotrypsin-type cysteine protease that is needed to produce functional proteins essential for virus replication and transcription. Serpin traps its target proteases by presenting a reactive center loop (RCL) as protease-specific cleavage site, resulting in protease inactivation. Mpro target sites with its active site serine and other flanking residues can possibly interact with serpins. Alternatively, RCL cleavage site of serpins with known evidence of inhibition of cysteine proteases can be replaced by Mpro target site to make chimeric proteins. Purified chimeric serpin can possibly inhibit Mpro that can be assessed indirectly by observing the decrease in ability of Mpro to cleave its chromogenic substrate. Chimeric serpins with best interaction and active site binding and with ability to form 11 serpin-Mpro complex in human plasma can be assessed by using SDS/PAGE and Western blot analysis with serpin antibody. Trapping SARS-CoV-2 Mpro cysteine protease using cross-class serpin cysteine protease inhibition activity is a novel idea with significant therapeutic potential.
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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Antivirales / Neumonía Viral / Serpinas / Proteínas no Estructurales Virales / Infecciones por Coronavirus / Betacoronavirus Tipo de estudio: Ensayo controlado aleatorizado Límite: Humanos Idioma: Inglés Revista: Clin Sci (Lond) Año: 2020 Tipo del documento: Artículo País de afiliación: CS20200767

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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Antivirales / Neumonía Viral / Serpinas / Proteínas no Estructurales Virales / Infecciones por Coronavirus / Betacoronavirus Tipo de estudio: Ensayo controlado aleatorizado Límite: Humanos Idioma: Inglés Revista: Clin Sci (Lond) Año: 2020 Tipo del documento: Artículo País de afiliación: CS20200767