Cargando…
New methylene blue derivatives suggest novel anti-orthopoxviral strategies
Decades after the eradication of smallpox and the discontinuation of routine smallpox vaccination, over half of the world's population is immunologically naïve to variola virus and other orthopoxviruses (OPXVs). Even in those previously vaccinated against smallpox, protective immunity wanes ove...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s). Published by Elsevier B.V.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9629033/ https://www.ncbi.nlm.nih.gov/pubmed/33992710 http://dx.doi.org/10.1016/j.antiviral.2021.105086 |
_version_ | 1784823318812033024 |
---|---|
author | Priyamvada, Lalita Burgado, Jillybeth Baker-Wagner, Marissa Kitaygorodskyy, Anatoliy Olson, Victoria Lingappa, Vishwanath R. Satheshkumar, Panayampalli Subbian |
author_facet | Priyamvada, Lalita Burgado, Jillybeth Baker-Wagner, Marissa Kitaygorodskyy, Anatoliy Olson, Victoria Lingappa, Vishwanath R. Satheshkumar, Panayampalli Subbian |
author_sort | Priyamvada, Lalita |
collection | PubMed |
description | Decades after the eradication of smallpox and the discontinuation of routine smallpox vaccination, over half of the world's population is immunologically naïve to variola virus and other orthopoxviruses (OPXVs). Even in those previously vaccinated against smallpox, protective immunity wanes over time. As such, there is a concomitant increase in the incidence of human OPXV infections worldwide. To identify novel antiviral compounds with potent anti-OPXV potential, we characterized the inhibitory activity of PAV-866 and other methylene blue derivatives against the prototypic poxvirus, vaccinia virus (VACV). These compounds inactivated virions prior to infection and consequently inhibited viral binding, fusion and entry. The compounds exhibited strong virucidal activity at non-cytotoxic concentrations, and inhibited VACV infection when added before, during or after viral adsorption. The compounds were effective against other OPXVs including monkeypox virus, cowpox virus and the newly identified Akhmeta virus. Altogether, these findings reveal a novel mode of inhibition that has not previously been demonstrated for small molecule compounds against VACV. Additional studies are in progress to determine the in vivo efficacy of these compounds against OPXVs and further characterize the anti-viral effects of these derivatives. |
format | Online Article Text |
id | pubmed-9629033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Author(s). Published by Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96290332022-11-03 New methylene blue derivatives suggest novel anti-orthopoxviral strategies Priyamvada, Lalita Burgado, Jillybeth Baker-Wagner, Marissa Kitaygorodskyy, Anatoliy Olson, Victoria Lingappa, Vishwanath R. Satheshkumar, Panayampalli Subbian Antiviral Res Research Paper Decades after the eradication of smallpox and the discontinuation of routine smallpox vaccination, over half of the world's population is immunologically naïve to variola virus and other orthopoxviruses (OPXVs). Even in those previously vaccinated against smallpox, protective immunity wanes over time. As such, there is a concomitant increase in the incidence of human OPXV infections worldwide. To identify novel antiviral compounds with potent anti-OPXV potential, we characterized the inhibitory activity of PAV-866 and other methylene blue derivatives against the prototypic poxvirus, vaccinia virus (VACV). These compounds inactivated virions prior to infection and consequently inhibited viral binding, fusion and entry. The compounds exhibited strong virucidal activity at non-cytotoxic concentrations, and inhibited VACV infection when added before, during or after viral adsorption. The compounds were effective against other OPXVs including monkeypox virus, cowpox virus and the newly identified Akhmeta virus. Altogether, these findings reveal a novel mode of inhibition that has not previously been demonstrated for small molecule compounds against VACV. Additional studies are in progress to determine the in vivo efficacy of these compounds against OPXVs and further characterize the anti-viral effects of these derivatives. The Author(s). Published by Elsevier B.V. 2021-07 2021-05-13 /pmc/articles/PMC9629033/ /pubmed/33992710 http://dx.doi.org/10.1016/j.antiviral.2021.105086 Text en © 2021 The Author(s) Elsevier has created a Monkeypox Information Center (https://www.elsevier.com/connect/monkeypox-information-center) in response to the declared public health emergency of international concern, with free information in English on the monkeypox virus. The Monkeypox Information Center is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its monkeypox related research that is available on the Monkeypox Information Center - including this research content - immediately available in publicly funded repositories, 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 Monkeypox Information Center remains active. |
spellingShingle | Research Paper Priyamvada, Lalita Burgado, Jillybeth Baker-Wagner, Marissa Kitaygorodskyy, Anatoliy Olson, Victoria Lingappa, Vishwanath R. Satheshkumar, Panayampalli Subbian New methylene blue derivatives suggest novel anti-orthopoxviral strategies |
title | New methylene blue derivatives suggest novel anti-orthopoxviral strategies |
title_full | New methylene blue derivatives suggest novel anti-orthopoxviral strategies |
title_fullStr | New methylene blue derivatives suggest novel anti-orthopoxviral strategies |
title_full_unstemmed | New methylene blue derivatives suggest novel anti-orthopoxviral strategies |
title_short | New methylene blue derivatives suggest novel anti-orthopoxviral strategies |
title_sort | new methylene blue derivatives suggest novel anti-orthopoxviral strategies |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9629033/ https://www.ncbi.nlm.nih.gov/pubmed/33992710 http://dx.doi.org/10.1016/j.antiviral.2021.105086 |
work_keys_str_mv | AT priyamvadalalita newmethylenebluederivativessuggestnovelantiorthopoxviralstrategies AT burgadojillybeth newmethylenebluederivativessuggestnovelantiorthopoxviralstrategies AT bakerwagnermarissa newmethylenebluederivativessuggestnovelantiorthopoxviralstrategies AT kitaygorodskyyanatoliy newmethylenebluederivativessuggestnovelantiorthopoxviralstrategies AT olsonvictoria newmethylenebluederivativessuggestnovelantiorthopoxviralstrategies AT lingappavishwanathr newmethylenebluederivativessuggestnovelantiorthopoxviralstrategies AT satheshkumarpanayampallisubbian newmethylenebluederivativessuggestnovelantiorthopoxviralstrategies |