ACE2: THE DOORWAY TO SARS-CoV-2

Medina-Enríquez, Miriam Marlene; Carlos-Escalante, José Alberto; Aponte-Torres, Zuleika; Cuapio, Angélica; López-Léon, Sandra; Wegman-Ostrosky, Talía

doi:10.31226/osf.io/bhpx8

Cited by 5 publications

(5 citation statements)

References 99 publications

(121 reference statements)

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“…1). The S1 fragment includes an N-terminal domain (NTD) and a receptor-binding domain (RBD), the latter mediating virus interaction with the cell surface receptor angiotensin-converting enzyme 2 (ACE2) (31). The S2 fragment is responsible for S-protein trimerization and contains fusion domains that are essential for virus entry.…”

Section: Introductionmentioning

confidence: 99%

Rotavirus as an Expression Platform of the SARS-CoV-2 Spike Protein

Philip

Patton

2021

Preprint

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Rotavirus, a segmented double-stranded RNA virus, is a major cause of acute gastroenteritis in young children. The introduction of live oral rotavirus vaccines has reduced the incidence of rotavirus disease in many countries. To explore the possibility of establishing a combined rotavirus-SARS-CoV-2 vaccine, we generated recombinant (r)SA11 rotaviruses with modified segment 7 RNAs that contained coding sequences for NSP3 and FLAG-tagged portions of the SARS-CoV-2 spike (S) protein. A 2A translational element was used to drive separate expression of NSP3 and the S product. rSA11 viruses were recovered that encoded the S-protein S1 fragment, N-terminal domain (NTD), receptor-binding domain (RBD), extended receptor-binding domain (ExRBD), and S2 core (CR) domain (rSA11/NSP3-fS1, -fNTD, -fRBD, -fExRBD, and -fCR, respectively). Generation of rSA11/fS1 required a foreign-sequence insertion of 2.2-kbp, the largest such insertion yet made into the rotavirus genome. Based on isopycnic centrifugation, rSA11 containing S sequences were denser than wildtype virus, confirming the capacity of the rotavirus to accommodate larger genomes. Immunoblotting showed that rSA11/-fNTD, -fRBD, -fExRBD, and -fCR viruses expressed S products of expected size, with fExRBD expressed at highest levels. These rSA11 viruses were genetically stable during serial passage. In contrast, rSA11/NSP3-fS1 failed to express its expected 80-kDa fS1 product, for unexplained reasons. Moreover, rSA11/NSP3-fS1 was genetically unstable, with variants lacking the S1 insertion appearing during serial passage. Nonetheless, these results emphasize the potential usefulness of rotavirus vaccines as expression vectors of portions of the SARS-CoV-2 S protein (e.g., NTD, RBD, ExRBD, and CR) with sizes smaller than the S1 fragment.

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Section: Introductionmentioning

confidence: 99%

Rotavirus as an Expression Platform of the SARS-CoV-2 Spike Protein

Philip

Patton

2021

Preprint

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“…Due to DNA damage was accumulated during aging, our findings provide an explanation of age associated severity and outcome of COVID-19, although other characteristics and alterations of aging could not be excluded. Apart from aging, other factors involved in COVID-19 progression, such as smoking and obesity, were associated with ACE2 expression [34][35][36] . Moreover, both smoking and obesity could cause, or at least associate with the level of DNA damage 37,38 , which suggest a potential role of DNA damage in smoking and obesity related risk of COVID-19.…”

Section: E and F Fig S4 E And F) Amentioning

confidence: 99%

DNA damage contributes to age-associated differences in SARS-CoV-2 infection

Jin

Niu

et al. 2021

Preprint

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Coronavirus disease 2019 (COVID-19), caused by coronavirus SARS-CoV-2, is known to disproportionately affect older individuals. Age is the most important determinant of disease severity and mortality. How aging processes affect the disease progression remains largely unknown. Here we found that DNA damage, a common denominator and major cause of aging, promoted susceptibility to SARS-CoV-2 infection in cells and intestinal organoids. SARS-CoV-2 entry was facilitated by DNA damage caused by either telomere attrition or extrinsic genotoxic stress and hampered by inhibition of DNA damage response. Mechanistic analysis revealed that the DNA damage response increased expression of ACE2, the receptor of SARS-CoV-2, by activation of transcription factor c-Jun in vitro and in vivo. Knockdown of c-Jun significantly reduced cell susceptibility to SARS-CoV-2. To explore the clinical clues of contribution of DNA damage in SARS-CoV-2 infection, we analyzed the expression of ACE2, γH2Ax and p-c-Jun in old and young human and mouse tissues. Expression of ACE2 was elevated in older human and mouse tissues and positively correlated with γH2Ax and p-c-Jun. Finally, targeting DNA damage by increasing the DNA repair capacity, alleviated cell susceptibility to SARS-CoV-2. Our data provide insight into the age-associated differences in SARS-CoV-2 infection and a novel target for anti-viral intervention.

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“…ACE2 is an important component of Renin-Angiotensin System (RAS). The circulatory RAS is composed of certain enzymes and active-inactive peptides and plays crucial roles in human body including the regulation of blood pressure, fluid volumes and electrolyte homeostasis [22][23][24][25][26][27]. These regulations are controlled through the digestion of Angiotensinogen by Renin to generate Angiotensin I and transformation of Angiotensin I to the active form Angiotensin II by angiotensinconverting enzyme (ACE).…”

Section: Ace2 and Tmprss2 Expression Profiles In Ocular Tissuesmentioning

confidence: 99%

Potency of SARS-CoV-2 on Ocular Tissues

Durak¹,

Sutova²,

Yetisgin³

et al. 2021

Infectious Eye Diseases - Recent Advances in Diagnosis and Treatment

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The current COVID-19 pandemic has affected more than 100 million people and resulted in morbidity and mortality around the world. Even though the disease caused by SARS-CoV-2 is characterized by respiratory tract involvement, previous and recent data also indicates ocular manifestation. Not surprisingly, cell entry point of the virus, ACE2 receptor, is widely expressed in ocular tissues ranging from conjunctiva to retina. Despite the sensibility of ocular tissues, the sophisticated defense mechanism of the eye might eliminate viral transmission. Nevertheless, the potential of systemic transmission through the nasolacrimal duct may not be eliminated. In the case of ocular involvement, the disease outcomes might be as treatable as conjunctivitis or as serious as retinal degeneration and the treatment regimen vary accordingly. Within these contingencies, our aim with this chapter is to shed light on molecular bases of SARS-CoV-2 infection, systemic invasiveness following ocular transmission, manifestation and permanent effects on ocular tissues.

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ACE2: THE DOORWAY TO SARS-CoV-2

Cited by 5 publications

References 99 publications

Rotavirus as an Expression Platform of the SARS-CoV-2 Spike Protein

Rotavirus as an Expression Platform of the SARS-CoV-2 Spike Protein

DNA damage contributes to age-associated differences in SARS-CoV-2 infection

Potency of SARS-CoV-2 on Ocular Tissues

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