Effect of remdesivir post-exposure prophylaxis and treatment on pathogenesis of measles in rhesus macaques

Measles is a systemic disease initiated in the respiratory tract with widespread measles virus (MeV) infection of lymphoid tissue. Mortality can be substantial, but no licensed antiviral therapy is available. We evaluated both post-exposure prophylaxis and treatment with remdesivir, a broad-spectrum...

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Main Author: Peart Akindele N.A.
Other Authors: Mahidol University
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Published: 2023
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/82100
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spelling th-mahidol.821002023-05-19T14:50:47Z Effect of remdesivir post-exposure prophylaxis and treatment on pathogenesis of measles in rhesus macaques Peart Akindele N.A. Mahidol University Multidisciplinary Measles is a systemic disease initiated in the respiratory tract with widespread measles virus (MeV) infection of lymphoid tissue. Mortality can be substantial, but no licensed antiviral therapy is available. We evaluated both post-exposure prophylaxis and treatment with remdesivir, a broad-spectrum antiviral, using a well-characterized rhesus macaque model of measles. Animals were treated with intravenous remdesivir for 12 days beginning either 3 days after intratracheal infection (post-exposure prophylaxis, PEP) or 11 days after infection at the onset of disease (late treatment, LT). As PEP, remdesivir lowered levels of viral RNA in peripheral blood mononuclear cells, but RNA rebounded at the end of the treatment period and infectious virus was continuously recoverable. MeV RNA was cleared more rapidly from lymphoid tissue, was variably detected in the respiratory tract, and not detected in urine. PEP did not improve clinical disease nor lymphopenia and reduced the antibody response to infection. In contrast, LT had little effect on levels of viral RNA or the antibody response but also did not decrease clinical disease. Therefore, remdesivir transiently suppressed expression of viral RNA and limited dissemination when provided as PEP, but virus was not cleared and resumed replication without improvement in the clinical disease parameters evaluated. 2023-05-19T07:50:47Z 2023-05-19T07:50:47Z 2023-12-01 Article Scientific Reports Vol.13 No.1 (2023) 10.1038/s41598-023-33572-7 20452322 37081035 2-s2.0-85153438837 https://repository.li.mahidol.ac.th/handle/123456789/82100 SCOPUS
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Multidisciplinary
spellingShingle Multidisciplinary
Peart Akindele N.A.
Effect of remdesivir post-exposure prophylaxis and treatment on pathogenesis of measles in rhesus macaques
description Measles is a systemic disease initiated in the respiratory tract with widespread measles virus (MeV) infection of lymphoid tissue. Mortality can be substantial, but no licensed antiviral therapy is available. We evaluated both post-exposure prophylaxis and treatment with remdesivir, a broad-spectrum antiviral, using a well-characterized rhesus macaque model of measles. Animals were treated with intravenous remdesivir for 12 days beginning either 3 days after intratracheal infection (post-exposure prophylaxis, PEP) or 11 days after infection at the onset of disease (late treatment, LT). As PEP, remdesivir lowered levels of viral RNA in peripheral blood mononuclear cells, but RNA rebounded at the end of the treatment period and infectious virus was continuously recoverable. MeV RNA was cleared more rapidly from lymphoid tissue, was variably detected in the respiratory tract, and not detected in urine. PEP did not improve clinical disease nor lymphopenia and reduced the antibody response to infection. In contrast, LT had little effect on levels of viral RNA or the antibody response but also did not decrease clinical disease. Therefore, remdesivir transiently suppressed expression of viral RNA and limited dissemination when provided as PEP, but virus was not cleared and resumed replication without improvement in the clinical disease parameters evaluated.
author2 Mahidol University
author_facet Mahidol University
Peart Akindele N.A.
format Article
author Peart Akindele N.A.
author_sort Peart Akindele N.A.
title Effect of remdesivir post-exposure prophylaxis and treatment on pathogenesis of measles in rhesus macaques
title_short Effect of remdesivir post-exposure prophylaxis and treatment on pathogenesis of measles in rhesus macaques
title_full Effect of remdesivir post-exposure prophylaxis and treatment on pathogenesis of measles in rhesus macaques
title_fullStr Effect of remdesivir post-exposure prophylaxis and treatment on pathogenesis of measles in rhesus macaques
title_full_unstemmed Effect of remdesivir post-exposure prophylaxis and treatment on pathogenesis of measles in rhesus macaques
title_sort effect of remdesivir post-exposure prophylaxis and treatment on pathogenesis of measles in rhesus macaques
publishDate 2023
url https://repository.li.mahidol.ac.th/handle/123456789/82100
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