key: cord-1030378-3bfbu872 authors: Parit, R.A.H.U.L.; Jayavel, S.R.I.D.H.A.R. title: Association of ACE inhibitors and Angiotensin type II blockers with ACE2 overexpression in COVID-19 comorbidities: a pathway-based analytical study date: 2021-01-27 journal: Eur J Pharmacol DOI: 10.1016/j.ejphar.2021.173899 sha: 06b8c3fdf8cf1bc8852675a920024543a4cda53f doc_id: 1030378 cord_uid: 3bfbu872 Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) outbreak is a major public health concern, which has accounted for >1.7 million deaths across the world. A surge in the case fatality ratio as compared with the infection ratio has been observed in most of the countries. The novel Coronavirus SARS-CoV-2 shares the most common sequence with SARS-CoV, but it has a higher rate of transmission. The SARS-CoV-2 pathogenesis is initiated by the binding of viral spike protein with the target receptor Angiotensin-Converting Enzyme 2 (ACE2) facilitating virus internalization within host cells. SARS-CoV-2 mainly causes alveolar damage ranging from mild to severe clinical respiratory manifestations. Most of the cases have revealed the association of Coronavirus disease with patients having earlier comorbidities like Hypertension, Diabetes mellitus, and Cerebrovascular diseases. Pharmacological investigation of the SARS-Cov-2 patients has revealed the frequent use of drugs belongs to Angiotensin-converting enzyme inhibitors (ACEi) and/or Angiotensin II type I receptor blockers (ARBs). Interestingly, a significant increase in ACE2 expression was noticed in patients routinely treated with the above group of drugs were also reported. To date, the association of ACEi and/or ARBs with the up-regulation of ACE2 expression has not been defined distinctively. The proposed review will focus on the pathways which are responsible for the upregulation of ACE2 and its impact on gravity of SARS-CoV-2 disease. researchers have suggested their concern on switching towards an alternative 244 pharmacological agent for therapeutic intervention. Thus Angiotensin-Converting Enzyme 2 (ACE2) Is a Key 711 Modulator of the Renin Angiotensin System in Health and Disease Tissue specific up regulation of ACE2 in rabbit model of atherosclerosis by 715 atorvastatin: role of epigenetic histone modifications A 718 human homolog of angiotensin-converting enzyme. Cloning and functional expression as 719 a captopril-insensitive carboxypeptidase Hyperglycemia and insulin resistance: possible mechanisms ACE2 Cell Biology, Regulation, and Physiological Functions. The 725 Protective Arm of the Renin Angiotensin System (RAS) ACE2: from vasopeptidase to SARS 728 virus receptor The NLRP3 inflammasome instigates 732 obesity-induced inflammation and insulin resistance Hydrolysis of biological peptides by human angiotensin-converting enzyme-related 737 carboxypeptidase Receptor recognition by the 740 novel coronavirus from Wuhan: an analysis based on decade-long structural studies of 741 SARS coronavirus Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan Converting Enzyme 2 Metabolizes and Partially Inactivates Pyr-Apelin-13 and Apelin-751 17: Physiological Effects in the Cardiovascular System Preventing a covid-19 pandemic Summary table of SARS cases by country A new coronavirus associated with human 764 respiratory disease in China ACE and ACE2 activity in diabetic mice Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain 771 in spike protein ACEIs/ARBs for the prevention of type2 diabetes in 774 patients with cardiovasculardiseases: a systematic review and meta-analysis Clinical course and 778 outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a 779 single-centered, retrospective, observational study the TGF-beta/Smad signaling pathway in rabbits 2020 b . Clinical characteristics of 140 patients infected with SARS-CoV-2 in 788 Preservation of Glucagon-Like Peptide-1 Level Attenuates 792 Angiotensin II-Induced Tissue Fibrosis by Altering AT1/AT 2 Receptor Expression and 793 Enzyme 2 Activity in Rat Heart 2020 a . Molecular and serological investigation of 2019-797 nCoV infected patients: implication of multiple shedding routes