Repositioning PARP inhibitors for SARS-CoV-2 infection(COVID-19); a new multi-pronged therapy for acute respiratory distress syndrome?

被引：53

作者：

Curtin, Nicola ^{[1
]}

Banyai, Krisztian ^{[2
]}

Thaventhiran, James ^{[3
]}

Le Quesne, John ^{[3
,4
,5
]}

Helyes, Zsuzsanna ^{[6
,7
,8
]}

Bai, Peter ^{[9
,10
,11
]}

机构：

[1] Newcastle Univ, Ctr Canc, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, Tyne & Wear, England

[2] Ctr Agr Res, Inst Vet Med Res, Budapest, Hungary

[3] Univ Cambridge, MRC Toxicol Unit, Leicester, Leics, England

[4] Univ Leicester, Leicester Canc Res Ctr, Leicester Royal Infirm, Leicester, Leics, England

[5] Univ Hosp Leicester NHS Trust, Glenfield Hosp, Leicester, Leics, England

[6] Univ Pecs, Med Sch, Dept Pharmacol & Pharmacotherapy, Pecs, Hungary

[7] Univ Pecs, Ctr Neurosci, Pecs, Hungary

[8] Univ Pecs, Janos Szentagothai Res Ctr, Pecs, Hungary

[9] Univ Debrecen, Dept Med Chem, Fac Med, Egyet Ter 1, H-4032 Debrecen, Hungary

[10] MTA DE Lendulet Lab Cellular Metab, Debrecen, Hungary

[11] Univ Debrecen, Res Ctr Mol Med, Fac Med, Debrecen, Hungary

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 2020年 / 177卷 / 16期

基金：

匈牙利科学研究基金会; 英国医学研究理事会;

关键词：

ADP-RIBOSE POLYMERASE; ACUTE LUNG INJURY; CORONAVIRUS NUCLEOCAPSID PROTEIN; GRADE OVARIAN-CARCINOMA; IN-VITRO EXPOSURE; POLY(ADP-RIBOSE) POLYMERASE; MAINTENANCE THERAPY; POTENT INHIBITOR; CYTOKINE STORM; DOUBLE-BLIND;

D O I：

10.1111/bph.15137

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Clinically approved PARP inhibitors (PARPi) have a mild adverse effect profile and are well tolerated as continuous daily oral therapy. We review the evidence that justifies the repurposing of PARPi to block the proliferation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and combat the life-threatening sequelae of coronavirus disease 2019 (COVID-19) by several mechanisms. PARPi can effectively decrease IL-6, IL-1 and TNF-alpha levels (key interleukins in SARS-CoV-2-induced cytokine storm) and can alleviate subsequent lung fibrosis, as demonstrated in murine experiments and clinical trials. PARPi can tune macrophages towards a tolerogenic phenotype. PARPi may also counteract SARS-CoV-2-induced and inflammation-induced cell death and support cell survival. PARPi is effective in animal models of acute respiratory distress syndrome (ARDS), asthma and ventilator-induced lung injury. PARPi may potentiate the effectiveness of tocilizumab, anakinra, sarilumab, adalimumab, canakinumab or siltuximab therapy. The evidence suggests that PARPi would benefit COVID-19 patients and trials should be undertaken.

引用

页码：3635 / 3645

页数：11

共 105 条

[81] Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients [J].