Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets

COVID-19 is the name of the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that occurred in 2019. The virus–host-specific interactions, molecular targets on host cell deaths, and the involved signaling are crucial issues, which become potential targets f...

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Main Authors: Rittibet Yapasert, Patompong Khaw-on, Ratana Banjerdpongchai
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/24/7459
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author Rittibet Yapasert
Patompong Khaw-on
Ratana Banjerdpongchai
author_facet Rittibet Yapasert
Patompong Khaw-on
Ratana Banjerdpongchai
author_sort Rittibet Yapasert
collection DOAJ
description COVID-19 is the name of the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that occurred in 2019. The virus–host-specific interactions, molecular targets on host cell deaths, and the involved signaling are crucial issues, which become potential targets for treatment. Spike protein, angiotensin-converting enzyme 2 (ACE2), cathepsin L-cysteine peptidase, transmembrane protease serine 2 (TMPRSS2), nonstructural protein 1 (Nsp1), open reading frame 7a (ORF7a), viral main protease (3C-like protease (3CLpro) or Mpro), RNA dependent RNA polymerase (RdRp) (Nsp12), non-structural protein 13 (Nsp13) helicase, and papain-like proteinase (PLpro) are molecules associated with SARS-CoV infection and propagation. SARS-CoV-2 can induce host cell death via five kinds of regulated cell death, i.e., apoptosis, necroptosis, pyroptosis, autophagy, and PANoptosis. The mechanisms of these cell deaths are well established and can be disrupted by synthetic small molecules or natural products. There are a variety of compounds proven to play roles in the cell death inhibition, such as pan-caspase inhibitor (z-VAD-fmk) for apoptosis, necrostatin-1 for necroptosis, MCC950, a potent and specific inhibitor of the NLRP3 inflammasome in pyroptosis, and chloroquine/hydroxychloroquine, which can mitigate the corresponding cell death pathways. However, NF-κB signaling is another critical anti-apoptotic or survival route mediated by SARS-CoV-2. Such signaling promotes viral survival, proliferation, and inflammation by inducing the expression of apoptosis inhibitors such as Bcl-2 and XIAP, as well as cytokines, e.g., TNF. As a result, tiny natural compounds functioning as proteasome inhibitors such as celastrol and curcumin can be used to modify NF-κB signaling, providing a responsible method for treating SARS-CoV-2-infected patients. The natural constituents that aid in inhibiting viral infection, progression, and amplification of coronaviruses are also emphasized, which are in the groups of alkaloids, flavonoids, terpenoids, diarylheptanoids, and anthraquinones. Natural constituents derived from medicinal herbs have anti-inflammatory and antiviral properties, as well as inhibitory effects, on the viral life cycle, including viral entry, replication, assembly, and release of COVID-19 virions. The phytochemicals contain a high potential for COVID-19 treatment. As a result, SARS-CoV-2-infected cell death processes and signaling might be of high efficacy for therapeutic targeting effects and yielding encouraging outcomes.
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spelling doaj.art-b31fb91fd34f4ca084a37e0dd1af619c2023-11-23T09:44:21ZengMDPI AGMolecules1420-30492021-12-012624745910.3390/molecules26247459Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic TargetsRittibet Yapasert0Patompong Khaw-on1Ratana Banjerdpongchai2Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandFaculty of Nursing, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandCOVID-19 is the name of the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that occurred in 2019. The virus–host-specific interactions, molecular targets on host cell deaths, and the involved signaling are crucial issues, which become potential targets for treatment. Spike protein, angiotensin-converting enzyme 2 (ACE2), cathepsin L-cysteine peptidase, transmembrane protease serine 2 (TMPRSS2), nonstructural protein 1 (Nsp1), open reading frame 7a (ORF7a), viral main protease (3C-like protease (3CLpro) or Mpro), RNA dependent RNA polymerase (RdRp) (Nsp12), non-structural protein 13 (Nsp13) helicase, and papain-like proteinase (PLpro) are molecules associated with SARS-CoV infection and propagation. SARS-CoV-2 can induce host cell death via five kinds of regulated cell death, i.e., apoptosis, necroptosis, pyroptosis, autophagy, and PANoptosis. The mechanisms of these cell deaths are well established and can be disrupted by synthetic small molecules or natural products. There are a variety of compounds proven to play roles in the cell death inhibition, such as pan-caspase inhibitor (z-VAD-fmk) for apoptosis, necrostatin-1 for necroptosis, MCC950, a potent and specific inhibitor of the NLRP3 inflammasome in pyroptosis, and chloroquine/hydroxychloroquine, which can mitigate the corresponding cell death pathways. However, NF-κB signaling is another critical anti-apoptotic or survival route mediated by SARS-CoV-2. Such signaling promotes viral survival, proliferation, and inflammation by inducing the expression of apoptosis inhibitors such as Bcl-2 and XIAP, as well as cytokines, e.g., TNF. As a result, tiny natural compounds functioning as proteasome inhibitors such as celastrol and curcumin can be used to modify NF-κB signaling, providing a responsible method for treating SARS-CoV-2-infected patients. The natural constituents that aid in inhibiting viral infection, progression, and amplification of coronaviruses are also emphasized, which are in the groups of alkaloids, flavonoids, terpenoids, diarylheptanoids, and anthraquinones. Natural constituents derived from medicinal herbs have anti-inflammatory and antiviral properties, as well as inhibitory effects, on the viral life cycle, including viral entry, replication, assembly, and release of COVID-19 virions. The phytochemicals contain a high potential for COVID-19 treatment. As a result, SARS-CoV-2-infected cell death processes and signaling might be of high efficacy for therapeutic targeting effects and yielding encouraging outcomes.https://www.mdpi.com/1420-3049/26/24/7459coronavirusSARS-CoV-2COVID-19cell deathtargeted therapynatural compounds
spellingShingle Rittibet Yapasert
Patompong Khaw-on
Ratana Banjerdpongchai
Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets
Molecules
coronavirus
SARS-CoV-2
COVID-19
cell death
targeted therapy
natural compounds
title Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets
title_full Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets
title_fullStr Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets
title_full_unstemmed Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets
title_short Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets
title_sort coronavirus infection associated cell death signaling and potential therapeutic targets
topic coronavirus
SARS-CoV-2
COVID-19
cell death
targeted therapy
natural compounds
url https://www.mdpi.com/1420-3049/26/24/7459
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AT patompongkhawon coronavirusinfectionassociatedcelldeathsignalingandpotentialtherapeutictargets
AT ratanabanjerdpongchai coronavirusinfectionassociatedcelldeathsignalingandpotentialtherapeutictargets