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1.
Rev Med Virol ; 31(6): e2221, 2021 11.
Article in English | MEDLINE | ID: covidwho-1575100

ABSTRACT

The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ systems. Damage induced by the virus is related to dysfunctional activity of the immune system, but the activity of molecules such as C-reactive protein (CRP) as a factor capable of inducing an inflammatory status that may be involved in the severe evolution of the disease, has not been extensively evaluated. A systematic review was performed using the NCBI-PubMed database to find articles related to Covid-19 immunity, inflammatory response, and CRP published from December 2019 to December 2020. High levels of CRP were found in patients with severe evolution of Covid-19 in which several organ systems were affected and in patients who died. CRP activates complement, induces the production of pro-inflammatory cytokines and induces apoptosis which, together with the inflammatory status during the disease, can lead to a severe outcome. Several drugs can decrease the level or block the effect of CRP and might be useful in the treatment of Covid-19. From this review it is reasonable to conclude that CRP is a factor that can contribute to severe evolution of Covid-19 and that the use of drugs able to lower CRP levels or block its activity should be evaluated in randomized controlled clinical trials.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , C-Reactive Protein/antagonists & inhibitors , COVID-19/drug therapy , Complement System Proteins/immunology , Cytokine Release Syndrome/drug therapy , SARS-CoV-2/pathogenicity , ADAM17 Protein/antagonists & inhibitors , ADAM17 Protein/genetics , ADAM17 Protein/immunology , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Biomarkers/blood , C-Reactive Protein/genetics , C-Reactive Protein/immunology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Celecoxib/therapeutic use , Complement System Proteins/genetics , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Cytokines/antagonists & inhibitors , Cytokines/genetics , Cytokines/immunology , Disease Progression , Doxycycline/therapeutic use , Gene Expression Regulation , Humans , Randomized Controlled Trials as Topic , Severity of Illness Index , Survival Analysis
2.
Biomolecules ; 11(7)2021 07 16.
Article in English | MEDLINE | ID: covidwho-1323103

ABSTRACT

Cyclooxygenase-2 (COX-2) is an important enzyme involved in prostaglandins biosynthesis from arachidonic acid. COX-2 is frequently overexpressed in human cancers and plays a major tumor promoting function. Accordingly, many efforts have been devoted to efficiently target the catalytic site of this enzyme in cancer cells, by using COX-2 specific inhibitors such as celecoxib. However, despite their potent anti-tumor properties, the myriad of detrimental effects associated to the chronic inhibition of COX-2 in healthy tissues, has considerably limited their use in clinic. In addition, increasing evidence indicate that these anti-cancerous properties are not strictly dependent on the inhibition of the catalytic site. These findings have led to the development of non-active COX-2 inhibitors analogues aiming at preserving the antitumor effects of COX-2 inhibitors without their side effects. Among them, two celecoxib derivatives, 2,5-Dimethyl-Celecoxib and OSU-03012, have been developed and suggested for the treatment of viral (e.g., recently SARS-CoV-2), inflammatory, metabolic diseases and cancers. These molecules display stronger anti-tumor properties than celecoxib and thus may represent promising anti-cancer molecules. In this review, we discuss the impact of these two analogues on cancerous processes but also their potential for cancer treatment alone or in combination with existing approaches.


Subject(s)
Antineoplastic Agents/therapeutic use , Celecoxib/therapeutic use , Cyclooxygenase 2 Inhibitors/therapeutic use , Neoplasms/drug therapy , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Celecoxib/adverse effects , Celecoxib/analogs & derivatives , Celecoxib/pharmacology , Cell Cycle/drug effects , Cyclooxygenase 2 Inhibitors/adverse effects , Cyclooxygenase 2 Inhibitors/chemistry , Cyclooxygenase 2 Inhibitors/pharmacology , Humans , Pyrazoles/adverse effects , Pyrazoles/chemistry , Pyrazoles/pharmacology , Sulfonamides/adverse effects , Sulfonamides/chemistry , Sulfonamides/pharmacology
3.
Clin Appl Thromb Hemost ; 27: 10760296211003983, 2021.
Article in English | MEDLINE | ID: covidwho-1159169

ABSTRACT

COVID-19 (Coronavirus Disease 2019) is a highly contagious infection and associated with high mortality rates, primarily in elderly; patients with heart failure; high blood pressure; diabetes mellitus; and those who are smokers. These conditions are associated to increase in the level of the pulmonary epithelium expression of angiotensin-converting enzyme 2 (ACE-2), which is a recognized receptor of the S protein of the causative agent SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Severe cases are manifested by parenchymal lung involvement with a significant inflammatory response and the development of microvascular thrombosis. Several factors have been involved in developing this prothrombotic state, including the inflammatory reaction itself with the participation of proinflammatory cytokines, endothelial dysfunction/endotheliitis, the presence of antiphospholipid antibodies, and possibly the tissue factor (TF) overexpression. ARS-Cov-19 ACE-2 down-regulation has been associated with an increase in angiotensin 2 (AT2). The action of proinflammatory cytokines, the increase in AT2 and the presence of antiphospholipid antibodies are known factors for TF activation and overexpression. It is very likely that the overexpression of TF in COVID-19 may be related to the pathogenesis of the disease, hence the importance of knowing the aspects related to this protein and the therapeutic strategies that can be derived. Different therapeutic strategies are being built to curb the expression of TF as a therapeutic target for various prothrombotic events; therefore, analyzing this treatment strategy for COVID-19-associated coagulopathy is rational. Medications such as celecoxib, cyclosporine or colchicine can impact on COVID-19, in addition to its anti-inflammatory effect, through inhibition of TF.


Subject(s)
COVID-19/drug therapy , COVID-19/metabolism , Celecoxib/therapeutic use , Colchicine/therapeutic use , Cyclosporine/therapeutic use , SARS-CoV-2/metabolism , Thromboplastin/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/epidemiology , Cytokines/metabolism , Humans
4.
Int J Infect Dis ; 101: 29-32, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-807590

ABSTRACT

Coronavirus-triggered pulmonary and systemic disease, i.e. systemic inflammatory response to virally triggered lung injury, named COVID-19, and ongoing discussions on refining immunomodulation in COVID-19 without COX2 inhibition prompted us to search the related literature to show a potential target (COX2) and a weapon (celecoxib). The concept of selectively targeting COX2 and closely related cascades might be worth trying in the treatment of COVID-19 given the substantial amount of data showing that COX2, p38 MAPK, IL-1b, IL-6 and TGF-ß play pivotal roles in coronavirus-related cell death, cytokine storm and pulmonary interstitial fibrosis. Considering the lack of definitive treatment and importance of immunomodulation in COVID-19, COX2 inhibition might be a valuable adjunct to still-evolving treatment strategies. Celecoxib has properties that should be evaluated in randomized controlled studies and is also available for off-label use.


Subject(s)
COVID-19/drug therapy , Celecoxib/therapeutic use , Cyclooxygenase 2 Inhibitors/therapeutic use , Drug Repositioning , SARS-CoV-2 , Coronavirus Infections/drug therapy , Humans
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