# Comparison of Selected Characteristics of SARS-CoV-2, SARS-CoV, and HCoV-NL63
## 2 Conclusions  
Prior to 2003, only mild forms of coronavirus diseases were reported in humans. They caused inflammation of the upper and, rarely, lower respiratory tract. CoVs were much more common as pathogens of wild animals [15]. After 2003, severe pandemic forms of human CoVs emerged: SARS-CoV, MERS-CoV, and SARS-CoV-2 [65]. Zoonotic transmission was identified in all human CoVs. The primary hosts of CoVs are several genera of bats, transmissible to humans via an intermediate host [63,66]. The issue of SARS-CoV-2 transmission remains open. The disease is primarily transmitted from bat CoV RaTG13 in Chinese bats of the genus _Rhinolophidae_ with a significant match in gene nucleotides, via a probable secondary host, the rare pangolin species, which is has not been definitively confirmed due to differences in the genome in the S region of the binding spike protein [19]. Illnesses from COVID-19, SARS-CoV, and the less pathogenic HCov-NL63 have several characteristics in common. However, the mortality rate for SARS-CoV is much higher than for SARS-CoV-2. [67]. They cause respiratory diseases with a complicated and atypical course of pneumonia. HCov-NL63 is an endemic coronavirus strain [60]. The reduced pathogenicity of HCov-NL63 suggests that ACE2 binding by the virus is not the only factor that determines the severity of viral pathogenicity. The biggest difference between the viruses is that SARS-CoV has caused local outbreaks of severe pneumonia, whereas SARS-CoV-2 has affected the world. These viruses infect alveolar epithelial cells by occupying the ACE2 receptor on the cell surface. In the RBD of the S protein, the amino acid similarity between SARS-CoV-2 and SARS-CoV is only 73% [68,69]. The virion to the invaded cell occurs through the recognition site of the S protein receptor. The RBD of SARS-CoV-2 is at domain S1 at its N-terminal end; that of SARS is also in the S1 domain, but at its C-terminal end. Differences in ACE2 binding may result in more efficient occupation of the host cell receptor. The main difference between SARS-CoV-2 and SARS-CoV is the higher infectivity of the new virus. Previous studies have shown that the RBD of the SARS-CoV-2-S1 subunit has approximately 10- to 20-fold higher affinity to ACE2 than SARS-CoV RBD. SARS-CoV-2 S also has a potential furin cleavage site in the S1/S2 region, which is unique to SARS-like CoV. The CoV infects the target cell by either cytoplasmic or endosomal membrane fusion. Therefore, the fusion capacity of CoV-S is a leading indicator of the infectivity of the corresponding virus [70]. The role of proteases in the penetration of SARS-CoV-2 is essential for activation and recognition to the cell surface and, secondarily, for the penetration of the virus into the cell. The action of the membrane protease TMPRSS2 plays an important role, with fusion of the cell surface membrane and the virus subsequently penetrating the cytoplasm of the host cell. Of interest in therapy for hypertensive patients with COVID-19 is the question of continuing therapy with RAAS inhibitors or omitting ARB drugs. Serological levels of ACE2 are usually low. At present, the effects of RAAS inhibitor (ARB) therapy on ACE2 in humans are currently unknown. ACE inhibitors and ARBs have different effects on angiotensin II, the primary substrate of ACE2. The effects of these substances on ACE2 levels and activity may therefore vary. Despite the considerable structural homology between ACE and ACE2, their enzyme sites are different; therefore, ACE inhibitors do not directly affect ACE2 activity. The use of ACE inhibitors in ARB-type drugs is common worldwide. The effect of RAAS blockers on ACE2 levels suggests that omission of ACE blockers may be detrimental rather than beneficial in patients with lung injury. At this time, there are no data supporting RAAS antagonists worsen the prognosis of patients with COVID-19. Other studies have shown evidence that there is no association between RAAS antagonists and COVID-19.