Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Findings coming from autopsies and serum of SARS patients suggest an important immune-inflammatory implication in the evolution to respiratory distress. Conditions such as HIV infection or treatment with immunosuppressors (in cancer or autoimmune diseases) are not among the bad prognosis factors for development of distress. To date, there have been no reported case fatalities in children, probably due to their more immature immune system. Our conclusions follow: (1) The milder form of SARS in children and the apparent protective factor that immunosupression represent rules out a significant viral cytopathic effect (they would be the most affected). (2) The evidence for immune implication in distress strongly supports immunomodulators for therapy: phosphodiesterase inhibitors (due to their down-modulating activity on proinflammatory cytokines); inhaled corticoids (aimed at producing a local immunomodulation); teophylline or nedocromil sodium (which prevents inflammatory cell recruitment into the airway wall). (3) An early immunomodulatory therapy, based on the levels of proinflammatory cytokines and clinical parameters to evaluate the respiratory function such as arterial oxygen saturation, could prevent the occurrence of distress. (4) Vaccine design should consider the immune origin of distress. (5) Physicians should be aware of mildly symptomatic patients (children, immuno-compromised hosts) to avoid transmission to immunocompetent adults.
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PMID:Severe acute respiratory syndrome, a pathological immune response to the new coronavirus--implications for understanding of pathogenesis, therapy, design of vaccines, and epidemiology. 1567 50

Although most patients with coronavirus disease 2019 (COVID-19) have a good prognosis, in some cases, the disease progresses rapidly, and the mortality rate is high. Some evidence suggests that infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produces a 'cytokine storm', which is related to acute respiratory distress syndrome or multi-organ dysfunction leading to physiological deterioration and death. It is important to highlight the state of hypercoagulability that can be triggered, involving microvascular thrombosis and vascular occlusive events, which are relevant to such poor outcomes. At present, no specific antiviral drug or vaccine is available for SARS-CoV-2 infection, and current research is aimed at preventing and mitigating damage to the target organs, mainly the lungs. In seeking therapies for patients with COVID-19, immunomodulators, cytokine antagonists and early anti-coagulation therapies have been tested in attempts to reduce the mortality rate. Pentoxifylline, a non-specific phosphodiesterase inhibitor widely used to improve the rheological properties of blood, has beneficial anti-inflammatory properties and can significantly reduce the serum levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1, tumour necrosis factor-alpha, C-reactive protein and other immunoregulators. It has also been found to exert anti-thrombotic, antioxidant and anti-fibrogenic actions. These properties could help to prevent or mitigate the inflammatory response and hypercoagulability that develop with SARS-CoV-2 infection, decreasing multi-organ dysfunction manifesting primarily as acute lung injury.
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PMID:Potential usefulness of pentoxifylline, a non-specific phosphodiesterase inhibitor with anti-inflammatory, anti-thrombotic, antioxidant, and anti-fibrogenic properties, in the treatment of SARS-CoV-2. 3270 89

We propose a new hypothesis that the established drug pentoxifylline deserves attention as a potential repurposed therapeutic for COVID-19. Pentoxifylline is an immunomodulator with anti-inflammatory properties. It is a nonselective phosphodiesterase inhibitor and through Adenosine A2A Receptor-mediated pathways reduces tumor necrosis factor alpha, interleukin 1, interleukin 6, and interferon gamma and may act to reduce tissue damage during the cytokine storm host response to SARS-CoV-2 infection. This agent has been used clinically for many years and has a favorable profile of safety and tolerability. Pre-clinical data support pentoxifylline as effective in cytokine-driven lung damage. Clinical studies of pentoxifylline in radiation and cytokine-induced lung damage in humans are positive and consistent with anti-inflammatory efficacy. Pentoxifylline is a readily available, off-patent and inexpensive drug, suitable for large-scale use including in resource-limited countries. Current trials of therapeutics are largely focused on the inhibition of viral processes. We advocate urgent randomized trials of pentoxifylline for COVID-19 as a complementary approach to target the host responses.
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PMID:Hypothesis: Pentoxifylline is a potential cytokine modulator therapeutic in COVID-19 patients. 3271 61

In March 2020, the World Health Organization declared the severe acute respiratory syndrome corona virus 2 (SARS-CoV2) infection to be a pandemic disease. SARS-CoV2 was first identified in China and, despite the restrictive measures adopted, the epidemic has spread globally, becoming a pandemic in a very short time. Though there is growing knowledge of the SARS-CoV2 infection and its clinical manifestations, an effective cure to limit its acute symptoms and its severe complications has not yet been found. Given the worldwide health and economic emergency issues accompanying this pandemic, there is an absolute urgency to identify effective treatments and reduce the post infection outcomes. In this context, phosphodiesterases (PDEs), evolutionarily conserved cyclic nucleotide (cAMP/cGMP) hydrolyzing enzymes, could emerge as new potential targets. Given their extended distribution and modulating role in nearly all organs and cellular environments, a large number of drugs (PDE inhibitors) have been developed to control the specific functions of each PDE family. These PDE inhibitors have already been used in the treatment of pathologies that show clinical signs and symptoms completely or partially overlapping with post-COVID-19 conditions (e.g., thrombosis, inflammation, fibrosis), while new PDE-selective or pan-selective inhibitors are currently under study. This review discusses the state of the art of the different pathologies currently treated with phosphodiesterase inhibitors, highlighting the numerous similarities with the disorders linked to SARS-CoV2 infection, to support the hypothesis that PDE inhibitors, alone or in combination with other drugs, could be beneficial for the treatment of COVID-19.
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PMID:Phosphodiesterase Inhibitors: Could They Be Beneficial for the Treatment of COVID-19? 3272 45

Continuous identification of suspected infectious cases is crucial to control the recent pandemic caused by the novel human coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Real-time polymerase chain reaction (real-time PCR) technology cannot be implemented easily and in large scale in some communities due to lack of resources and infrastructures. Here, we report a simple colorimetric strategy derived from linker-based single-component assembly of gold nanoparticle-core spherical nucleic acids (AuNP-core SNAs) for visual detection of PCR products of SARS-CoV-2 ribonucleic acid (RNA) template. A palindromic linker is designed based on SARS-CoV-2 specific E gene to program the identical colloidal SNAs into large assemblies along with a distinct red-to-purple color change. The linker acts as a probe of SARS-CoV-2 RNA in conventional PCR reaction. In the presence of the correct template the palindromic linker, which is complementary to a short region within the target amplicon, is cleaved by 5'-exonuclease activity of deoxyribonucleic acid (DNA) polymerase. Cleavage of the palindromic linker during the amplification process inhibits the single-component assembly formation of SNAs. So, positive and negative viral samples produce simply red and purple colors in the post PCR colorimetric test, respectively. Evaluation of the samples obtained from cases with laboratory-confirmed SARS-CoV-2 infection revealed that our assay can rival with real-time PCR method in sensitivity.
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PMID:Conventional PCR assisted single-component assembly of spherical nucleic acids for simple colorimetric detection of SARS-CoV-2. 3301 89

In December 2019, a new coronavirus, named SARS-CoV-2, has emerged from China causing pneumonia outbreaks first in the Wuhan region and have now spread worldwide but there are still no "specific drug" available. In the difficulty where new synthesized drug cannot be applied immediately to patients, "conventional drug in new use" becomes a feasible solution. Chloroquine, remdesivir, favipiravi, lopinavir, ribavirin or ritonavir have shown efficacy to inhibit coronavirus in vitro. Pentoxifylline, a drug with anti-inflammatory, immunomodulatory and bronchodilatory effects, previously showed efficacy to inhibit various viral infections. Immunological studies have shown that most patients with severe COVID-19 exhibit substantially elevated serum levels of pro-inflammatory cytokines. Pentoxifylline is a phosphodiesterase inhibitor that increases cyclic adenosine monophosphate levels, which in turn activate protein kinase, leading to a reduction in the synthesis of proinflammatory cytokines and immune cell migration. Here we propose pentoxifylline, a drug with low cost and toxicity, as a possible treatment for COVID-19 in basis of its interesting properties.
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PMID:Pentoxifylline, a drug with antiviral, anti-inflammatory and bronchodilatory effects may be a possible drug candidate for SARS-CoV-2. 3304 37