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1.
Adv Biomed Res ; 11: 16, 2022.
Article in English | MEDLINE | ID: covidwho-1780155

ABSTRACT

The emerging of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is associated with high morbidity and mortality rates globally. One of the most prominent characteristics of coronavirus disease-19 (COVID-19) is lymphopenia, which is in contrast to other viral infections. This controversy might be explained by the evaluation of impaired innate and adaptive immune responses, during the SARS-CoV-2 infection. During the innate immune response, poly-ADP-ribose polymerase hyperactivated due to virus entry and extensive DNA damage sequentially, leading to nicotinamide adenine dinucleotide (NAD)+ depletion, adenosine triphosphate depletion, and finally cell death. In contrast to the immune response against viral infections, cytotoxic T lymphocytes decline sharply in SARS-CoV-2 infection which might be due to infiltration and trapping in the lower respiratory tract. In addition, there are more factors proposed to involve in lymphopenia in COVID-19 infection such as the role of CD38, which functions as NADase and intensifies NAD depletion, which in turn affects NAD+-dependent Sirtuin proteins, as the regulators of cell death and viability. Lung tissue sequestration following cytokine storm supposed to be another reason for lymphopenia in COVID-19 patients. Protein 7a, as one of the virus-encoded proteins, induces apoptosis in various organ-derived cell lines. These mechanisms proposed to induce lymphopenia, although there are still more studies needed to clarify the underlying mechanisms for lymphopenia in COVID-19 patients.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319623

ABSTRACT

The emerging of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is associated with high morbidity and mortality rates globally. One of the most prominent characteristics of coronavirus disease-19 (COVID-19) is lymphopenia which is in contrast to other viral infections. This controversy might be explained by the evaluation of impaired innate and adaptive immune responses during the SARS-CoV-2 infection. During the innate immune response, poly-ADP-ribose polymerase (PARP) hyperactivated due to virus entry and extensive DNA damage sequentially leading to NAD+ depletion, ATP depletion and finally cell death. In contrast to the immune response against viral infections, cytotoxic T lymphocytes decline sharply in SARS-CoV-2 infection which might be due to infiltration and trapping in the lower respiratory tract. In addition, there are more factors proposed to involve in lymphopenia in COVID-19 infection like the role of CD38 which functions as NADase and intensifies NAD depletion which in turn affects NAD+ dependent Sirtuin proteins, as the regulators of cell death and viability. Lung tissue sequestration following cytokine storm supposed to be another reason for lymphopenia in COVID-19 patients. Protein 7a as one of the virus-encoded proteins induces apoptosis in various organ-derived cell lines. These mechanisms proposed to induce lymphopenia, although there are still more studies needed to clarify the underlying mechanisms for lymphopenia in COVID-19 patients.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314474

ABSTRACT

The emerging new Coronaviridae member, nCoV 19, outbreak announced a pandemic by WHO with an increased morbidity and mortality rate worldwide. nCoV 19 known as the third highly pathogen coronavirus in the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), the nCoV 19. The renin-angiotensin (RAS) signaling pathway, oxidative stress and cell death, cytokines storm and endothelial dysfunction are four major pathways involved in the pathogenesis of nCoV 19. Acute respiratory distress syndrome (ARDS) generally develops with a massive oxidative/nitrosative stress following virus entry and RAS activation. The DNA damage subsequent to oxidative burst activates poly-ADP ribose polymerase-1 (PARP-1), viral macrodomain (NSP3) poly (ADP-ribose) glycohydrolase (PARG) and transient receptor potential channel, melastatin 2 (TRPM2) in a sequential manner ultimately leading to apoptosis and necrosis due to NAD and ATP depletion. Regarding the molecular mechanisms involved in nCoV 19 pathogenesis, angiotensin II receptor blockers and/or PARP, PARG and TRPM2 blockers could be engaged as therapeutic candidates for inhibition of RAS and quenching oxidative stress, respectively. In this review, the molecular aspects of nCoV 19 pathogenesis would be studied precisely and possible therapeutic targets would be proposed. It is recommended to evaluate the proposed drugs and supplements via registered clinical trials along with conventional guideline-based multi-drug regimen.

4.
Front Mol Biosci ; 8: 813175, 2021.
Article in English | MEDLINE | ID: covidwho-1686504

ABSTRACT

Previous studies suggested that patients with comorbidities including cancer had a higher risk of mortality or developing more severe forms of COVID-19. The interaction of cancer and COVID-19 is unrecognized and potential long-term effects of COVID-19 on cancer outcome remain to be explored. Furthermore, whether COVID-19 increases the risk of cancer in those without previous history of malignancies, has not yet been studied. Cancer progression, recurrence and metastasis depend on the complex interaction between the tumor and the host inflammatory response. Extreme proinflammatory cytokine release (cytokine storm) and multi-organ failure are hallmarks of severe COVID-19. Besides impaired T-Cell response, elevated levels of cytokines, growth factors and also chemokines in the plasma of patients in the acute phase of COVID-19 as well as tissue damage and chronic low-grade inflammation in "long COVID-19" syndrome may facilitate cancer progression and recurrence. Following a systemic inflammatory response syndrome, some counterbalancing compensatory anti-inflammatory mechanisms will be activated to restore immune homeostasis. On the other hand, there remains the possibility of the integration of SARS- CoV-2 into the host genome, which potentially may cause cancer. These mechanisms have also been shown to be implicated in both tumorigenesis and metastasis. In this review, we are going to focus on potential mechanisms and the molecular interplay, which connect COVID-19, inflammation, and immune-mediated tumor progression that may propose a framework to understand the possible role of COVID-19 infection in tumorgenesis and cancer progression.

5.
Int J Mol Sci ; 22(11)2021 May 21.
Article in English | MEDLINE | ID: covidwho-1244038

ABSTRACT

In late 2019, a new member of the Coronaviridae family, officially designated as "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), emerged and spread rapidly. The Coronavirus Disease-19 (COVID-19) outbreak was accompanied by a high rate of morbidity and mortality worldwide and was declared a pandemic by the World Health Organization in March 2020. Within the Coronaviridae family, SARS-CoV-2 is considered to be the third most highly pathogenic virus that infects humans, following the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Four major mechanisms are thought to be involved in COVID-19 pathogenesis, including the activation of the renin-angiotensin system (RAS) signaling pathway, oxidative stress and cell death, cytokine storm, and endothelial dysfunction. Following virus entry and RAS activation, acute respiratory distress syndrome develops with an oxidative/nitrosative burst. The DNA damage induced by oxidative stress activates poly ADP-ribose polymerase-1 (PARP-1), viral macrodomain of non-structural protein 3, poly (ADP-ribose) glycohydrolase (PARG), and transient receptor potential melastatin type 2 (TRPM2) channel in a sequential manner which results in cell apoptosis or necrosis. In this review, blockers of angiotensin II receptor and/or PARP, PARG, and TRPM2, including vitamin D3, trehalose, tannins, flufenamic and mefenamic acid, and losartan, have been investigated for inhibiting RAS activation and quenching oxidative burst. Moreover, the application of organic and inorganic nanoparticles, including liposomes, dendrimers, quantum dots, and iron oxides, as therapeutic agents for SARS-CoV-2 were fully reviewed. In the present review, the clinical manifestations of COVID-19 are explained by focusing on molecular mechanisms. Potential therapeutic targets, including the RAS signaling pathway, PARP, PARG, and TRPM2, are also discussed in depth.


Subject(s)
COVID-19/drug therapy , COVID-19/therapy , Cytokine Release Syndrome/drug therapy , Nanomedicine/methods , Oxidative Stress/drug effects , Poly (ADP-Ribose) Polymerase-1/metabolism , SARS-CoV-2/drug effects , Apoptosis/drug effects , COVID-19/metabolism , COVID-19/physiopathology , Cholecalciferol/pharmacology , GTPase-Activating Proteins/antagonists & inhibitors , GTPase-Activating Proteins/metabolism , Humans , Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors , Renin-Angiotensin System/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/metabolism , TRPM Cation Channels/antagonists & inhibitors , TRPM Cation Channels/metabolism , Tannins/pharmacology , Trehalose/pharmacology
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