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Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the Sout...

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Autores principales: Ryu, Dong-Kyun, Song, Rina, Kim, Minsoo, Kim, Young-Il, Kim, Cheolmin, Kim, Jong-In, Kwon, Ki-Sung, Tijsma, Aloys SL., Nuijten, Patricia M., van Baalen, Carel A., Hermanus, Tandile, Kgagudi, Prudence, Moyo-Gwete, Thandeka, Moore, Penny L., Choi, Young Ki, Lee, Soo-Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180667/
https://www.ncbi.nlm.nih.gov/pubmed/34119826
http://dx.doi.org/10.1016/j.bbrc.2021.06.016
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author Ryu, Dong-Kyun
Song, Rina
Kim, Minsoo
Kim, Young-Il
Kim, Cheolmin
Kim, Jong-In
Kwon, Ki-Sung
Tijsma, Aloys SL.
Nuijten, Patricia M.
van Baalen, Carel A.
Hermanus, Tandile
Kgagudi, Prudence
Moyo-Gwete, Thandeka
Moore, Penny L.
Choi, Young Ki
Lee, Soo-Young
author_facet Ryu, Dong-Kyun
Song, Rina
Kim, Minsoo
Kim, Young-Il
Kim, Cheolmin
Kim, Jong-In
Kwon, Ki-Sung
Tijsma, Aloys SL.
Nuijten, Patricia M.
van Baalen, Carel A.
Hermanus, Tandile
Kgagudi, Prudence
Moyo-Gwete, Thandeka
Moore, Penny L.
Choi, Young Ki
Lee, Soo-Young
author_sort Ryu, Dong-Kyun
collection PubMed
description The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant.
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spelling pubmed-81806672021-06-07 Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant Ryu, Dong-Kyun Song, Rina Kim, Minsoo Kim, Young-Il Kim, Cheolmin Kim, Jong-In Kwon, Ki-Sung Tijsma, Aloys SL. Nuijten, Patricia M. van Baalen, Carel A. Hermanus, Tandile Kgagudi, Prudence Moyo-Gwete, Thandeka Moore, Penny L. Choi, Young Ki Lee, Soo-Young Biochem Biophys Res Commun Article The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant. Elsevier Inc. 2021-08-20 2021-06-07 /pmc/articles/PMC8180667/ /pubmed/34119826 http://dx.doi.org/10.1016/j.bbrc.2021.06.016 Text en © 2021 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Ryu, Dong-Kyun
Song, Rina
Kim, Minsoo
Kim, Young-Il
Kim, Cheolmin
Kim, Jong-In
Kwon, Ki-Sung
Tijsma, Aloys SL.
Nuijten, Patricia M.
van Baalen, Carel A.
Hermanus, Tandile
Kgagudi, Prudence
Moyo-Gwete, Thandeka
Moore, Penny L.
Choi, Young Ki
Lee, Soo-Young
Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant
title Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant
title_full Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant
title_fullStr Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant
title_full_unstemmed Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant
title_short Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant
title_sort therapeutic effect of ct-p59 against sars-cov-2 south african variant
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180667/
https://www.ncbi.nlm.nih.gov/pubmed/34119826
http://dx.doi.org/10.1016/j.bbrc.2021.06.016
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