References supporting angiotensin receptors for CoViD

Drug Dev Res. 2020 Aug;81(5):537-540. doi: 10.1002/ddr.21656. Epub 2020 Mar 4.

Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics

David Gurwitz 1

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PMID: 32129518 PMCID: PMC7228359 DOI: 10.1002/ddr.21656

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At the time of writing this commentary (February 2020), the coronavirus COVID-19 epidemic has already resulted in more fatalities compared with the SARS and MERS coronavirus epidemics combined. Therapeutics that may assist to contain its rapid spread and reduce its high mortality rates are urgently needed. Developing vaccines against the SARS-CoV-2 virus may take many months. Moreover, vaccines based on viral-encoded peptides may not be effective against future coronavirus epidemics, as virus mutations could make them futile. Indeed, new Influenza virus strains emerge every year, requiring new immunizations. A tentative suggestion based on existing therapeutics, which would likely be resistant to new coronavirus mutations, is to use available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the aggressiveness and mortality from SARS-CoV-2 virus infections. This idea is based on observations that the angiotensin-converting enzyme 2 (ACE2) very likely serves as the binding site for SARS-CoV-2, the strain implicated in the current COVID-19 epidemic, similarly to strain SARS-CoV implicated in the 2002-2003 SARS epidemic. This commentary elaborates on the idea of considering AT1R blockers as tentative treatment for SARS-CoV-2 infections, and proposes a research direction based on datamining of clinical patient records for assessing its feasibility.



IEEE/ACM Trans Comput Biol Bioinform. 2020 Jul 14;PP. doi: 10.1109/TCBB.2020.3009099. Online ahead of print.

AGTR2, one possible novel key gene for the entry of SARS-CoV-2 into human cells

Chunmei Cui, Chuanbo Huang, Wanlu Zhou, Xiangwen Ji, Fenghong Zhang, Liang Wang, Yuan Zhou, Qinghua Cui


Recently, it was confirmed that ACE2 is the receptor of SARS-CoV-2, the pathogen causing the recent outbreak of severe pneumonia around the world. It is confused that ACE2 is widely expressed across a variety of organs and is expressed moderately but not highly in lung, which, however, is the major infected organ. Therefore, we hypothesized that there could be some other genes playing key roles in the entry of SARS-CoV-2 into human cells. Here we found that AGTR2 (angiotensin II receptor type 2), a G-protein coupled receptor, has interaction with ACE2 and is highly expressed in lung with a high tissue specificity. More importantly, simulation of 3D structure based protein-protein interaction reveals that AGTR2 shows a higher binding affinity with the Spike protein of SARS-CoV-2 than ACE2 (energy: -8.2 vs. -5.1 [kcal/mol]). A number of compounds, biologics and traditional Chinese medicine that could decrease the expression level of AGTR2 were predicted. Finally, we suggest that AGTR2 could be a putative novel gene for the the entry of SARS-CoV-2 into human cells, which could provide different insight for the research of SARS-COV-2 proteins with their receptors.



Eur J Pharmacol. 2012 May 15;683(1-3):310-5. doi: 10.1016/j.ejphar.2012.02.032. Epub 2012 Feb 24.

Des-aspartate-angiotensin I exerts antiviral effects and attenuates ICAM-1 formation in rhinovirus-infected epithelial cells

Lay-Teng Ang 1, Ling-Yin Tan, Vincent T Chow, Meng-Kwoon Sim

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PMID: 22387854 DOI: 10.1016/j.ejphar.2012.02.032


The high frequency of rhinovirus (RV) infection and the lack of an effective treatment, underline the importance of research on novel anti-rhinoviral agents. The present study investigated the effects of des-aspartate-angiotensin I (DAA-I) on the survival of RV14-infected H1HeLa cells; and the early inflammatory processes in RV14-infected A549 lung epithelial cells. The study rationale was based on earlier findings showing that DAA-I is an effective anti-inflammatory agent, and that symptoms and severity of rhinoviral infection are related to the underling inflammation. RV14 concentration dependently caused the death of H1HeLa cells and DAA-I, at concentrations of 10⁻¹⁰ to 10⁻¹² M, attenuated the lethal action of RV14 indicating that that DAA-I exerts antiviral action. Unlike its action on H1HeLa cells, RV14 did not cause apparent cytopathic effect on A549 cells, and these cells were used to study the antiviral action of DAA-I. RV14 induced overexpression of ICAM-1, E-selectin and overproduction of superoxide in A549 cells, and DAA-I attenuated the three increases to basal level at concentrations of 10⁻¹⁰ to 10⁻¹² M. Losartan, an angiotensin AT₁ receptor antagonist, blocked the inhibitory action of DAA-I on superoxide overproduction indicating that the AT₁ receptor mediates the action of DAA-I. The present data represent a novel demonstration of the antiviral action of an angiotensin peptide, and a possible involvement of the renin angiotensin system in viral infection. Indeed the angiotensin AT₁ receptor has been reported to be obligatory for the development of virus-induced myocardial injury through the proinflammatory action of angiotensin II via the NF-κB/cytokine pathway.