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Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load
Despite extensive efforts, COVID-19 pandemic caused by the SARS-CoV-2 virus is still at large. Vaccination is an effective approach to curb virus spread, but several variants (e.g., delta, delta plus, omicron, and IHU) appear to weaken or possibly escape immune protection. Thus, novel and quickly sc...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AAAS
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918953/ https://www.ncbi.nlm.nih.gov/pubmed/35321260 http://dx.doi.org/10.34133/2022/9802969 |
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author | Maimaitiyiming, Yasen Yang, Tao Wang, Qian Qian Feng, Yan Chen, Zhi Björklund, Mikael Wang, Fudi Hu, Chonggao Hsu, Chih-Hung Naranmandura, Hua |
author_facet | Maimaitiyiming, Yasen Yang, Tao Wang, Qian Qian Feng, Yan Chen, Zhi Björklund, Mikael Wang, Fudi Hu, Chonggao Hsu, Chih-Hung Naranmandura, Hua |
author_sort | Maimaitiyiming, Yasen |
collection | PubMed |
description | Despite extensive efforts, COVID-19 pandemic caused by the SARS-CoV-2 virus is still at large. Vaccination is an effective approach to curb virus spread, but several variants (e.g., delta, delta plus, omicron, and IHU) appear to weaken or possibly escape immune protection. Thus, novel and quickly scalable approaches to restrain SARS-CoV-2 are urgently needed. Multiple evidences showed thermal sensitivity of SARS-CoV-2 and negative correlation between environmental temperature and COVID-19 transmission with unknown mechanism. Here, we reveal a potential mechanism by which mild heat treatment destabilizes the wild-type RNA-dependent RNA polymerase (also known as nonstructural protein 12 (NSP12)) of SARS-CoV-2 as well as the P323L mutant commonly found in SARS-CoV-2 variants, including omicron and IHU. Mechanistically, heat treatment promotes E3 ubiquitin ligase ZNF598-dependent NSP12 ubiquitination leading to proteasomal degradation and significantly decreases SARS-CoV-2 RNA copy number and viral titer. A mild daily heat treatment maintains low levels of both wild-type and P323L mutant of NSP12, suggesting clinical potential. Collectively, this novel mechanism, heat-induced NSP12 degradation, suggests a prospective heat-based intervention against SARS-CoV-2. |
format | Online Article Text |
id | pubmed-8918953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | AAAS |
record_format | MEDLINE/PubMed |
spelling | pubmed-89189532022-03-22 Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load Maimaitiyiming, Yasen Yang, Tao Wang, Qian Qian Feng, Yan Chen, Zhi Björklund, Mikael Wang, Fudi Hu, Chonggao Hsu, Chih-Hung Naranmandura, Hua Research (Wash D C) Perspective Despite extensive efforts, COVID-19 pandemic caused by the SARS-CoV-2 virus is still at large. Vaccination is an effective approach to curb virus spread, but several variants (e.g., delta, delta plus, omicron, and IHU) appear to weaken or possibly escape immune protection. Thus, novel and quickly scalable approaches to restrain SARS-CoV-2 are urgently needed. Multiple evidences showed thermal sensitivity of SARS-CoV-2 and negative correlation between environmental temperature and COVID-19 transmission with unknown mechanism. Here, we reveal a potential mechanism by which mild heat treatment destabilizes the wild-type RNA-dependent RNA polymerase (also known as nonstructural protein 12 (NSP12)) of SARS-CoV-2 as well as the P323L mutant commonly found in SARS-CoV-2 variants, including omicron and IHU. Mechanistically, heat treatment promotes E3 ubiquitin ligase ZNF598-dependent NSP12 ubiquitination leading to proteasomal degradation and significantly decreases SARS-CoV-2 RNA copy number and viral titer. A mild daily heat treatment maintains low levels of both wild-type and P323L mutant of NSP12, suggesting clinical potential. Collectively, this novel mechanism, heat-induced NSP12 degradation, suggests a prospective heat-based intervention against SARS-CoV-2. AAAS 2022-02-23 /pmc/articles/PMC8918953/ /pubmed/35321260 http://dx.doi.org/10.34133/2022/9802969 Text en Copyright © 2022 Yasen Maimaitiyiming et al. https://creativecommons.org/licenses/by/4.0/Exclusive Licensee Science and Technology Review Publishing House. Distributed under a Creative Commons Attribution License (CC BY 4.0). |
spellingShingle | Perspective Maimaitiyiming, Yasen Yang, Tao Wang, Qian Qian Feng, Yan Chen, Zhi Björklund, Mikael Wang, Fudi Hu, Chonggao Hsu, Chih-Hung Naranmandura, Hua Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load |
title | Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load |
title_full | Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load |
title_fullStr | Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load |
title_full_unstemmed | Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load |
title_short | Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load |
title_sort | heat treatment promotes ubiquitin-mediated proteolysis of sars-cov-2 rna polymerase and decreases viral load |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918953/ https://www.ncbi.nlm.nih.gov/pubmed/35321260 http://dx.doi.org/10.34133/2022/9802969 |
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