BJP: PARP inhibitors are expected to be potential therapeutic drugs for covid-19?

From: Medical Mission Hills < br / > currently, the global research and development of drugs and vaccines for covid-19 is ongoingRecent studies have shown that IL-6 receptor inhibitors, PARP inhibitors, RNAi therapy, polyclonal Hyperimmunoglobulin (h-ig) and other therapies with different mechanisms may be helpful for the treatment of covid-19Recently, a new study provides new evidence for PARP inhibitors to prevent the proliferation of new coronavirus (sars-cov-2)The article points out that PARP inhibitors can fight against the sequelae of covid-19 through several different mechanisms< br / > this article is published in the British Journal of Pharmacology (BJP)It is pointed out that PARP inhibitors can effectively reduce the levels of IL-6, IL-1 and TNF - α, and reduce the subsequent pulmonary fibrosis, which is consistent with the results of early animal experiments and clinical studiesThe study also showed that PARP inhibitor can also counteract the cell death induced by sars-cov-2 and inflammationIn the animal model, it can improve the lung injury induced by ARDS, asthma and ventilator< br / > we know that patients with sars-cov-2 infection often have over activation of the immune systemImmune cells continue to over express a large number of proinflammatory cytokines, including IFN, IL, chemokines and TNF, which lead to the failure of tissues and organs in patients and eventually lead to deathThe findings provide novel coronavirus pneumonia inhibitors for PARP patients to reduce the risk of cytokine storm< br / > according to previous studies, after the viral pneumonia patients are cured, the lung tissue will appear the change of pulmonary fibrosis during the repair process after the inflammatory reactionAccording to the clinicopathological analysis of critical patients with covid-19, a large number of pulmonary fibrosis can be observed in critical patients with covid-19, which may lead to severe respiratory failure in critical patientsThe effect of PARP inhibitors proposed in this paper is consistent with a previous study published in the Journal of drug discovery todayThis article about "PARP" ing fibrosis points out the role of poly ADP ribose polymerase (PARP) in fibrosis of main organs such as lung, heart, liver, kidney, etcthe author thinks that PARP inhibitors have certain therapeutic potential in anti fibrosis of organs< br / > in view of the fact that the inhibition of PARP can reduce the expression of human IL-6, the authors of this study suggest that PARP inhibitors can also enhance the therapeutic effect of Anti-IL-6 antibody (sicilizumab, siluximab) or Anti-IL-6 receptor antibody (sarilumab)In addition, the researchers cited a lot of evidence that PARP inhibitors may enhance the efficacy of anakinra, adalimumab and canakinumabIt is pointed out that PARP inhibitors may benefit patients with covid-19, and it is necessary to carry out clinical trials of these drugs (combined therapy)< br / > in fact, previous studies have suggested that PARP inhibitors can be used to treat covid-19< br / > in March this year, Zeng Jianyang research group of Tsinghua University and Zhu Fengcai research group of Jiangsu CDC published research papers on biorxivResearchers developed a data-driven drug repositioning framework, using the past SARS CoV and mers cov data for retrospective research, and found a potential anti SARS cov-2 drug cvl218< br / > according to the public information, cvl218 is a poly ADP ribose polymerase 1 (PARP1) inhibitor developed by Shanghai Institute of medicine, Chinese Academy of SciencesAccording to the public information of Shanghai Institute of pharmaceutical research, Chinese Academy of Sciences, the researchers used natural like structure to design drugs and carried out a series of structural optimization, and finally obtained this new PARP inhibitor mefuparib hydrochlorideAt present, the study of cvl218 for tumor treatment has been in the clinical 1 / 2 phase trial stage< br / > since the outbreak of the new crown epidemic, researchers have also carried out a series of research on the drug related to sars-cov-2The results showed that cvl218 could inhibit the replication of sars-cov-2 effectively, and had no obvious cytopathic effectIn addition, cvl218 can inhibit the production of IL-6 induced by CpG in peripheral blood monocytes, which indicates that cvl218 may have anti-inflammatory effect highly related to the prevention of immunopathology caused by sars-cov-2 infection< br / > further pharmacokinetic and toxicokinetic evaluation in rats and monkeys showed that the concentration of cvl218 in the lung was very high and there was no evidence of toxicityThis suggests that the candidate drug has certain potential in the treatment of sars-cov-2-induced pneumoniaThe results of molecular docking simulation suggest that cvl218 may bind to the N-terminal domain of the Nucleocapsid (n) protein of sars-cov-2, which may explain the antiviral mechanism of the candidate drug to some extent< br / > based on the data in this study and the evidence reported in previous literature, the researchers proposed several possible mechanisms to explain the antiviral activity of PARP1 inhibitor to sars-cov-2Cvl218, an inhibitor of PARP1 discovered by the data-driven drug repositioning framework, is expected to be a potential drug for the treatment of covid-19 < br / > it is reported that cvl218 is being developed globally by convalife Fukang health technology is a new drug R & D company in the clinical stage, which is committed to developing innovative drugs in the field of anti-tumor and anti-aging diseases for the whole world It is reported that the company plans to carry out clinical research on the drug in the United States, which will be used to treat solid tumor patients infected with covid-19 At present, the company has received a positive written response from the FDA on the pre ind meeting < br / > it is worth noting that an article published online at the end of may in the international medical journal Lancet analyzed the clinical effect of covid-19 on cancer patients The article points out that the 30 day all-cause mortality rate of patients with cancer is very high, and there is a significant positive correlation with the specific risk factors of cancer patients At present, there are no clinical drugs for such special patients in the world < br / > the main indications of several PARP inhibitors approved for marketing in the world are breast cancer, ovarian cancer, pancreatic cancer, etc At the same time, PARP inhibitors are expected to expand to other cancer species If PARP inhibitors can benefit patients with covid-19, it will be a greater blessing for patients with cancer < br / > with the deepening of the research on new coronavirus and covid-19, more researches are being carried out around the world, hoping to provide help for the prevention and treatment of covid-19 We look forward to the smooth development of this research of Fukang health technology, and also look forward to the joint efforts of the scientific research community, the biomedical community and other parties to develop an effective covid-19 treatment drug as soon as possible and defeat sars-cov-2 as soon as possible ▽