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BMJ Open ; 10(9): e040644, 2020 09 14.
Article in English | MEDLINE | ID: covidwho-767942


OBJECTIVE: To review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate ACE2 and potentially affect COVID-19 disease. DESIGN: Systematic review. DATA SOURCE: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science. STUDY SELECTION: Any design with animal or human models examining a currently prescribed UK drug compared with a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression. DATA EXTRACTION AND SYNTHESIS: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1 April 2020. Methodological quality was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool for animal studies and Cochrane risk-of-bias tool for human studies. RESULTS: We screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and one hundred and two were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were angiotensin receptor blockers (ARBs) (n=55) and ACE inhibitors (ACE-I) (n=22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel blockers (n=3) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2). CONCLUSIONS: There is an abundance of the academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty among patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease.

Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Calcium Channel Blockers/pharmacology , Coronavirus Infections , Estrogens/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , Pandemics , Peptidyl-Dipeptidase A/drug effects , Pneumonia, Viral , Angiotensin-Converting Enzyme 2 , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Betacoronavirus/metabolism , COVID-19 , Down-Regulation , Glucagon-Like Peptide 1/agonists , Humans , Insulin/pharmacology , Mineralocorticoid Receptor Antagonists/pharmacology , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2 , Thiazolidinediones/pharmacology , United Kingdom , Up-Regulation
Viruses ; 12(4)2020 04 05.
Article in English | MEDLINE | ID: covidwho-31709


Porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) have been reported to use aminopeptidase N (APN) as a cellular receptor. Recently, the role of APN as a receptor for PEDV has been questioned. In our study, the role of APN in PEDV and TGEV infections was studied in primary porcine enterocytes. After seven days of cultivation, 89% of enterocytes presented microvilli and showed a two- to five-fold higher susceptibility to PEDV and TGEV. A significant increase of PEDV and TGEV infection was correlated with a higher expression of APN, which was indicative that APN plays an important role in porcine coronavirus infections. However, PEDV and TGEV infected both APN positive and negative enterocytes. PEDV and TGEV Miller showed a higher infectivity in APN positive cells than in APN negative cells. In contrast, TGEV Purdue replicated better in APN negative cells. These results show that an additional receptor exists, different from APN for porcine coronaviruses. Subsequently, treatment of enterocytes with neuraminidase (NA) had no effect on infection efficiency of TGEV, implying that terminal cellular sialic acids (SAs) are no receptor determinants for TGEV. Treatment of TGEV with NA significantly enhanced the infection which shows that TGEV is masked by SAs.

CD13 Antigens/metabolism , Gastroenteritis, Transmissible, of Swine/pathology , Porcine epidemic diarrhea virus/metabolism , Receptors, Virus/metabolism , Sialic Acids/metabolism , Transmissible gastroenteritis virus/metabolism , Animals , Cells, Cultured , Chlorocebus aethiops , Coronavirus Infections/pathology , Coronavirus Infections/veterinary , Enterocytes/virology , Hydrocortisone/pharmacology , Insulin/pharmacology , Respiratory Mucosa/virology , Spermidine/pharmacology , Swine , Vero Cells , Virus Attachment , Virus Replication/drug effects