BJP Published: PARP inhibitors expected to be a potential treatment for COVID-19?
Last Update: 2020-06-16
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Currently, global research and development of drugs and vaccines for COVID-19 continuesRecent studies have shown that treatments with a variety of different mechanisms of action, such as IL-6 receptor inhibitors, PARP inhibitors, RNAi therapy, and polyclonal superimmune globulin (H-IG), may be helpful in the treatment of COVID-19A recent study has provided new evidence for PARP inhibitors to prevent the proliferation of the new coronavirus (SARS-CoV-2), which suggests that PARP inhibitors can fight THE after-effects of COVID-19 through several different mechanismsThe article was published in the British Journal of Pharmacology (BJP)The paper points out that PARP inhibitors can effectively reduce the levels of interleukin 6 (IL-6), interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) and reduce subsequent pulmonary fibrosis, which is consistent with early animal studies and clinical studiesThe study also showed that PARP inhibitors can also counteract SARS-CoV-2-induced cell death, which in animal models has an improved effect on acute respiratory distress syndrome (ARDS), asthma, and ventilator-induced lung injuryWe know that SARS-CoV-2 infection patients often experience overactivation of the immune system, immune cells continue to express a large number of inflammatory cytokines including IFN, IL, chemochemical factors and TNF, which cause the patient's body organ functional failure, and ultimately lead to deathThe findings of this study provide a basis for PARP inhibitors to be used to reduce the risk of cytokine storms in patients with new coronary pneumoniaAccording to previous studies, after the cure of viral pneumonia, the lung tissue in the post-inflammatory response repair process, there will be changes in pulmonary fibrosisClinical pathology analysis of patients with COVID-19 critical conditions also showed that large amounts of pulmonary fibrosis can be observed in patients with COVID-19 critical condition, which can lead to severe respiratory failure in critically ill patientsThe effects of PARP inhibitors in this paper on reducing pulmonary fibrosis are consistent with a previous study published in the journal Drug Discovery TodayThis article about 'PARP' ing fibrosis points to the role of polyADP ribalycopolymerase (PARP) in fibrosis in major organs such as the lungs, heart, liver, kidneys, and the authors believe that PARP inhibitors have some therapeutic potential in combating organ fibrosisSince PARP inhibition reduces the expression of IL-6 in the body, the study authors suggest that PARP inhibitors can also enhance the therapeutic effectiveness of anti-IL-6 antibodies (tocilizumab, siltuximab) or anti-IL-6 receptor antibodies (sarilumab)In addition, the researchers cite a number of evidence that PARP inhibitors may enhance the efficacy of anakinra, adalimumab, and canakinumabThe article points out that PARP inhibitors have the potential to benefit patients with COVID-19, and that clinical trials of these drugs (combination therapies) are necessaryIn fact, previous studies have suggested that PARP inhibitors could be used to treat COVID-19In March this year, Tsinghua University's Zeng Jianyang and Jiangsu Province CDC Zhu Fengcai's team published a research paper on bioRxiv bioRxiv, a pre-printed bioRxiv, and researchers developed a data-driven drug repositioning framework, using past SARS-CoV and MERS-CoV data for retrospective research, to find a potential anti-SARS-CoV-2 drug CVL218 Public information shows that CVL218 is a polypolymer ADP ribonuclease polymerase 1 (PARP1) inhibitor developed by the Shanghai Institute of Pharmaceutical Research of the Chinese Academy of Sciences According to the information disclosed by the Shanghai Institute of Pharmaceutical Research of the Chinese Academy of Sciences, the researchers used a natural advantage structure to design the drug and perform a series of structural optimization, resulting in the new PARP inhibitor mefuparib hydrochloride At present, CVL218 is currently used in tumor therapy research has been in the clinical phase 1/2 trial stage Since the outbreak of the new crown, researchers have also conducted a series of studies related to the drug, SARS-CoV-2 The in vitro results showed that CVL218 to SARS-CoV-2 replication showed effective inhibition and no obvious cellular lesions In addition, CVL218 inhibits the production of CPG-induced IL-6 peripheral blood mononucleosis, suggesting that it may have an anti-inflammatory effect highly correlated with immunological lying prevention caused by SARS-CoV-2 infection Further pharmacokinetic and toxic metabolic dynamics assessments in rats and monkeys showed high concentrations of CVL218 in the lungs and no significant signs of toxicity This suggests that the candidate has some potential for treating pneumonia caused by SARS-CoV-2 Molecular docking simulation results suggest that CVL218 may be combined with the N-end domain of SARS-CoV-2 nuclear shell (N) protein, which may explain the antiviral mechanism of the candidate drug to a certain extent Based on data from this study and evidence reported in previous literature, the researchers have proposed several possible mechanisms to explain the antiviral activity of PARP1 inhibitors against SARS-CoV-2 It is believed that the PARP1 inhibitor CVL218, discovered in the framework of data-driven drug repositioning, is expected to be a potential drug for the treatment of COVID-19 It is reported that the current CVL218 is being developed globally by Convalife Fukang Health Technology is a clinical lysateure research and development company dedicated to the global development of anti-tumor and anti-aging diseases in the field of innovative drugs It is reported that the company plans to carry out clinical research on the drug in the United States, intended to treat patients infected with COVID-19 solid tumor Currently, the company has received a positive written response from the FDA regarding the Pre-IND meeting Notably, an article published online at the end of May in the international medical journal The Lancet analyzed the clinical effects of COVID-19 on cancer patients The article points out that the 30-day all-cause mortality rate of COVID-19 patients with cancer was high and was positively associated with the risk factors specific to cancer patients Currently, there are no clinical treatments for this particular patient worldwide Among several PARP inhibitors that have been approved for market around the world, the main indications are breast cancer, ovarian cancer, pancreatic cancer and so on At the same time, PARP inhibitors are expected to expand to other cancer species If PARP inhibitors benefit patients with COVID-19, it will be a greater boon for patients with cancer As research into the new coronavirus and COVID-19 becomes more intensive, more research is being carried out around the world in the hope of helping with COVID-19 prevention and treatment We look forward to the smooth development of this research of Fukang Health Technology, and we look forward to the early development of effective COVID-19 therapeutic drugs with the cooperation of the scientific research community, the biomedical community and other parties, and an early victory over SARS-CoV-2.
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