Nucleic Acid-Sensing Pathways During SARS-CoV-2 Infection: Expectations versus Reality

Bushra Mdkhana,1 Narjes Saheb Sharif-Askari,1 Rakhee K Ramakrishnan,1 Swati Goel,1 Qutayba Hamid,1– 3 Rabih Halwani1,2 1Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 2Department of Clinical Sciences, College of Medicine, U...

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Autores principales:	Mdkhana B, Saheb-Sharif Askari N, Ramakrishnan RK, Goel S, Hamid Q, Halwani R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	covid-19 sars-cov-2 innate immune system nucleic acid sensing immune evasion nlrp3 cgas-sting coronavirus Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/1d9b6ee24c174e1d9c3c7a0574a07e11
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spelling	oai:doaj.org-article:1d9b6ee24c174e1d9c3c7a0574a07e112021-12-02T14:08:53ZNucleic Acid-Sensing Pathways During SARS-CoV-2 Infection: Expectations versus Reality1178-7031https://doaj.org/article/1d9b6ee24c174e1d9c3c7a0574a07e112021-01-01T00:00:00Zhttps://www.dovepress.com/nucleic-acid-sensing-pathways-during-sars-cov-2-infection-expectations-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Bushra Mdkhana,1 Narjes Saheb Sharif-Askari,1 Rakhee K Ramakrishnan,1 Swati Goel,1 Qutayba Hamid,1– 3 Rabih Halwani1,2 1Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 2Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 3Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Montreal, Quebec, CanadaCorrespondence: Rabih HalwaniCollege of Medicine, University of Sharjah, Sharjah, United Arab EmiratesEmail rhalwani@sharjah.ac.aeAbstract: The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people and crippled economies worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for this pandemic has triggered avid research on its pathobiology to better understand the pathophysiology of COVID-19. In the absence of approved antiviral therapeutic strategies or vaccine platforms capable of effectively targeting this global threat, the hunt for effective therapeutics has led to many candidates being actively evaluated for their efficacy in controlling or preventing COVID-19. In this review, we gathered current evidence on the innate nucleic acid-sensing pathways expected to be elicited by SARS-CoV-2 and the immune evasion mechanisms they have developed to promote viral replication and infection. Within the nucleic acid-sensing pathways, SARS-CoV-2 infection and evasion mechanisms trigger the activation of NOD-signaling and NLRP3 pathways leading to the production of inflammatory cytokines, IL-1β and IL-6, while muting or blocking cGAS-STING and interferon type I and III pathways, resulting in decreased production of antiviral interferons and delayed innate response. Therefore, blocking the inflammatory arm and boosting the interferon production arm of nucleic acid-sensing pathways could facilitate early control of viral replication and dissemination, prevent disease progression, and cytokine storm development. We also discuss the rationale behind therapeutic modalities targeting these sensing pathways and their implications in the treatment of COVID-19.Keywords: COVID-19, SARS-CoV-2, innate immune system, nucleic acid sensing, immune evasion, NLRP3, cGAS-STING, coronavirusMdkhana BSaheb-Sharif Askari NRamakrishnan RKGoel SHamid QHalwani RDove Medical Pressarticlecovid-19sars-cov-2innate immune systemnucleic acid sensingimmune evasionnlrp3cgas-stingcoronavirusPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 199-216 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	covid-19 sars-cov-2 innate immune system nucleic acid sensing immune evasion nlrp3 cgas-sting coronavirus Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	covid-19 sars-cov-2 innate immune system nucleic acid sensing immune evasion nlrp3 cgas-sting coronavirus Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Mdkhana B Saheb-Sharif Askari N Ramakrishnan RK Goel S Hamid Q Halwani R Nucleic Acid-Sensing Pathways During SARS-CoV-2 Infection: Expectations versus Reality
description	Bushra Mdkhana,1 Narjes Saheb Sharif-Askari,1 Rakhee K Ramakrishnan,1 Swati Goel,1 Qutayba Hamid,1– 3 Rabih Halwani1,2 1Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 2Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 3Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Montreal, Quebec, CanadaCorrespondence: Rabih HalwaniCollege of Medicine, University of Sharjah, Sharjah, United Arab EmiratesEmail rhalwani@sharjah.ac.aeAbstract: The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people and crippled economies worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for this pandemic has triggered avid research on its pathobiology to better understand the pathophysiology of COVID-19. In the absence of approved antiviral therapeutic strategies or vaccine platforms capable of effectively targeting this global threat, the hunt for effective therapeutics has led to many candidates being actively evaluated for their efficacy in controlling or preventing COVID-19. In this review, we gathered current evidence on the innate nucleic acid-sensing pathways expected to be elicited by SARS-CoV-2 and the immune evasion mechanisms they have developed to promote viral replication and infection. Within the nucleic acid-sensing pathways, SARS-CoV-2 infection and evasion mechanisms trigger the activation of NOD-signaling and NLRP3 pathways leading to the production of inflammatory cytokines, IL-1β and IL-6, while muting or blocking cGAS-STING and interferon type I and III pathways, resulting in decreased production of antiviral interferons and delayed innate response. Therefore, blocking the inflammatory arm and boosting the interferon production arm of nucleic acid-sensing pathways could facilitate early control of viral replication and dissemination, prevent disease progression, and cytokine storm development. We also discuss the rationale behind therapeutic modalities targeting these sensing pathways and their implications in the treatment of COVID-19.Keywords: COVID-19, SARS-CoV-2, innate immune system, nucleic acid sensing, immune evasion, NLRP3, cGAS-STING, coronavirus
format	article
author	Mdkhana B Saheb-Sharif Askari N Ramakrishnan RK Goel S Hamid Q Halwani R
author_facet	Mdkhana B Saheb-Sharif Askari N Ramakrishnan RK Goel S Hamid Q Halwani R
author_sort	Mdkhana B
title	Nucleic Acid-Sensing Pathways During SARS-CoV-2 Infection: Expectations versus Reality
title_short	Nucleic Acid-Sensing Pathways During SARS-CoV-2 Infection: Expectations versus Reality
title_full	Nucleic Acid-Sensing Pathways During SARS-CoV-2 Infection: Expectations versus Reality
title_fullStr	Nucleic Acid-Sensing Pathways During SARS-CoV-2 Infection: Expectations versus Reality
title_full_unstemmed	Nucleic Acid-Sensing Pathways During SARS-CoV-2 Infection: Expectations versus Reality
title_sort	nucleic acid-sensing pathways during sars-cov-2 infection: expectations versus reality
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/1d9b6ee24c174e1d9c3c7a0574a07e11
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Nucleic Acid-Sensing Pathways During SARS-CoV-2 Infection: Expectations versus Reality

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