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Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice

Improving clinical care for individuals infected with SARS-CoV-2 variants is a global health priority. Small-molecule antivirals like remdesivir (RDV) and biologics such as human monoclonal antibodies (mAbs) have demonstrated therapeutic efficacy against SARS-CoV-2, the causative agent of coronaviru...

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Autores principales: Martinez, David R., Schäfer, Alexandra, Leist, Sarah R., Li, Dapeng, Gully, Kendra, Yount, Boyd, Feng, Joy Y., Bunyan, Elaine, Porter, Danielle P., Cihlar, Tomas, Montgomery, Stephanie A., Haynes, Barton F., Baric, Ralph S., Nussenzweig, Michel C., Sheahan, Timothy P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270748/
https://www.ncbi.nlm.nih.gov/pubmed/34289384
http://dx.doi.org/10.1016/j.celrep.2021.109450
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author Martinez, David R.
Schäfer, Alexandra
Leist, Sarah R.
Li, Dapeng
Gully, Kendra
Yount, Boyd
Feng, Joy Y.
Bunyan, Elaine
Porter, Danielle P.
Cihlar, Tomas
Montgomery, Stephanie A.
Haynes, Barton F.
Baric, Ralph S.
Nussenzweig, Michel C.
Sheahan, Timothy P.
author_facet Martinez, David R.
Schäfer, Alexandra
Leist, Sarah R.
Li, Dapeng
Gully, Kendra
Yount, Boyd
Feng, Joy Y.
Bunyan, Elaine
Porter, Danielle P.
Cihlar, Tomas
Montgomery, Stephanie A.
Haynes, Barton F.
Baric, Ralph S.
Nussenzweig, Michel C.
Sheahan, Timothy P.
author_sort Martinez, David R.
collection PubMed
description Improving clinical care for individuals infected with SARS-CoV-2 variants is a global health priority. Small-molecule antivirals like remdesivir (RDV) and biologics such as human monoclonal antibodies (mAbs) have demonstrated therapeutic efficacy against SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). It is not known whether combination RDV/mAb will improve outcomes over single-agent therapies or whether antibody therapies will remain efficacious against variants. Here, we show that a combination of two mAbs in clinical trials, C144 and C135, have potent antiviral effects against even when initiated 48 h after infection and have therapeutic efficacy in vivo against the B.1.351 variant of concern (VOC). Combining RDV and antibodies provided a modest improvement in outcomes compared with single agents. These data support the continued use of RDV to treat SARS-CoV-2 infections and the continued clinical development of the C144 and C135 antibody combination to treat patients infected with SARS-CoV-2 variants.
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spelling pubmed-82707482021-07-20 Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice Martinez, David R. Schäfer, Alexandra Leist, Sarah R. Li, Dapeng Gully, Kendra Yount, Boyd Feng, Joy Y. Bunyan, Elaine Porter, Danielle P. Cihlar, Tomas Montgomery, Stephanie A. Haynes, Barton F. Baric, Ralph S. Nussenzweig, Michel C. Sheahan, Timothy P. Cell Rep Article Improving clinical care for individuals infected with SARS-CoV-2 variants is a global health priority. Small-molecule antivirals like remdesivir (RDV) and biologics such as human monoclonal antibodies (mAbs) have demonstrated therapeutic efficacy against SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). It is not known whether combination RDV/mAb will improve outcomes over single-agent therapies or whether antibody therapies will remain efficacious against variants. Here, we show that a combination of two mAbs in clinical trials, C144 and C135, have potent antiviral effects against even when initiated 48 h after infection and have therapeutic efficacy in vivo against the B.1.351 variant of concern (VOC). Combining RDV and antibodies provided a modest improvement in outcomes compared with single agents. These data support the continued use of RDV to treat SARS-CoV-2 infections and the continued clinical development of the C144 and C135 antibody combination to treat patients infected with SARS-CoV-2 variants. The Author(s). 2021-07-27 2021-07-10 /pmc/articles/PMC8270748/ /pubmed/34289384 http://dx.doi.org/10.1016/j.celrep.2021.109450 Text en © 2021 The Author(s) 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
Martinez, David R.
Schäfer, Alexandra
Leist, Sarah R.
Li, Dapeng
Gully, Kendra
Yount, Boyd
Feng, Joy Y.
Bunyan, Elaine
Porter, Danielle P.
Cihlar, Tomas
Montgomery, Stephanie A.
Haynes, Barton F.
Baric, Ralph S.
Nussenzweig, Michel C.
Sheahan, Timothy P.
Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice
title Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice
title_full Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice
title_fullStr Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice
title_full_unstemmed Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice
title_short Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice
title_sort prevention and therapy of sars-cov-2 and the b.1.351 variant in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270748/
https://www.ncbi.nlm.nih.gov/pubmed/34289384
http://dx.doi.org/10.1016/j.celrep.2021.109450
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