ARTICLE | doi:10.20944/preprints202003.0308.v1
Online: 20 March 2020 (07:01:44 CET)
Novel coronavirus (COVID-19) can lead to multiple organ injuries such as acute respiratory distress syndrome (ARDS), acute renal injury (AKI) and so on. ACE2 is an important part of the renin-angiotensin system (RAS) and a key protein needed for COVID-19 to invade cells. First of all, we searched the HPA, GTEx and FANTOM5 Databases and found that the expression of ACE2 in kidney tissue was significantly higher than that in lung tissue. Then, by searching the Nephroseq Database, it is further verified that ACE2 is highly expressed in renal tissue and plays a protective role in renal tissue. However, current studies have found that the incidence of AKI caused by COVID-19 is much lower than that of ARDS. Because of this, we further searched the proteins interacting with ACE2 protein through the STING Database and analyzed the expression of tissue protein mRNA in the HPA Database. It was noted that AGTR2 mRNA was highly expressed in lung tissue, but low in kidney tissue, and hard tissue specificity in lung tissue. Through further research, it is found that AGTR2 plays a major role in the development of pulmonary fibrosis. Therefore, AGTR2 may be a key protein in COVID-19 pneumonia, and AGTR2 may be a potential new therapeutic target for the treatment of COVID-19 patients.
ARTICLE | doi:10.20944/preprints202002.0194.v1
Online: 14 February 2020 (10:52:21 CET)
Recently, it was confirmed that ACE2 is the receptor of 2019-nCoV, the pathogen causing the recent outbreak of severe pneumonia in China. 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. It remains unclear why it is the lung but not other tissues among which ACE2 highly expressed is mainly infected. We hypothesized that there could be some other genes playing key roles in the entry of 2019-nCoV 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 2019-nCov than ACE2 (energy score: -15.7 vs. -6.9 [kcal/mol]). Given these observations, we suggest that AGTR2 could be a putative novel gene for the the entry of 2019-nCoV into human cells but need further confirmation by biological experiments. Finally, a number of compounds, biologics and traditional Chinese medicine that could decrease the expression level of AGTR2 were predicted.
REVIEW | doi:10.20944/preprints202006.0120.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: SARS-CoV-2; COVID-19; pathogenesis; children; neonates; immune response; secondary hemophagocytic lymphohistiocytosis; renin-angiotensin system; genetic polymorphisms; ACE2; AGTR2; AGTR1; NOS; lung injury
Online: 9 June 2020 (08:07:40 CEST)
The spread of the infection caused by the new coronavirus SARS-CoV-2 (COVID-19) became pandemic on March 11, 2020. From the time of the first cases (in November 2019, Wuhan, China), to date, a large number of COVID-19 observations have been accumulated in different age groups of patients both in China and abroad. Published scientific data allows us to conclude that children suffer from COVID-19 much less often than adults and tolerate the disease in a milder form, often appear to be asymptomatic. There is currently no final answer why children are less susceptible to this virus; however, scientists are increasingly inclined to consider a complex effect of the immune response and components of the renin-angiotensin system (RAS), which according to recent studies affects not only the cardiovascular system, but is also responsible for the activation of inflammatory reactions. A hypothesis of genetic predisposition to the development of severe forms of COVID-19 has recently been made. We conducted a search for publications in the databases and showed current scientific ideas about COVID-19 pathogenesis and factors influencing the disease development in childhood. Childhood immunity may have several protective features against SARS-CoV-2: immaturity of particular elements of the innate immune response, constitutional lymphocytosis with a shift towards anti-inflammatory Th2-response, as well as "trained" immunity. The influence of renin-angiotensin system reactions in this review is shown from two perspectives: expression of ACE2 receptors and polymorphisms of certain genes of this system. It was established that ACE2 transmembrane protein is not only the entry point for the virus but also plays a regulatory role, turning the pro-inflammatory vasoconstrictor angiotensin II into anti-inflammatory angiotensin (1-7), which has vasodilating properties. Higher ACE2 content in children compared with adults helps maintain balance in the renin-angiotensin system and prevents the development of complications. It was also shown that the presence of certain genetic polymorphisms (AGTR1, AGTR2, ACE2, ACE) could determine the imbalance inside the RAS, leading to more pronounced reactions of alveolocytes, vascular endothelium and smooth muscle fibers in response to SARS-CoV-2 infection due to a shift towards vasoconstrictor, proliferative and profibrotic mechanisms.