Multivalent ACE2 engineering—A promising pathway for advanced coronavirus nanomedicine development

Obeng, Eugene M.; Fianu, Isaac; Danquah, Michael K.

doi:10.1016/j.nantod.2022.101580

Cited by 8 publications

(11 citation statements)

References 256 publications

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“…For example, Omicron has a significantly enhanced binding affinity for ACE2 compared to the original Wuhan strain virus (Kim et al, 2022c). Therefore, ACE2 exemplifies a 'meet change with constancy' target for COVID-19 drug discovery in that, unlike ever-mutating SARS-CoV-2 (Desai et al, 2021;Obeng et al, 2022), ACE2 in the host is unlikely to mutate. A ngiotensin-converting enzyme 2 is a key component of the renin-angiotensin system (RAS), which relaxes the vascular wall and is expressed in epithelial cells of the lung, colon, kidney, heart, and blood vessels under normal physiological conditions, which is essential for the proper functioning of the cardiovascular system, the inflammatory homeostasis of the body, and tissue health (Gheblawi et al, 2020;Trougakos et al, 2021).…”

Section:  Defence: Evs As a Nanodecoy To Defend Against Sars-cov- C...mentioning

confidence: 99%

“…For example, Omicron has a significantly enhanced binding affinity for ACE2 compared to the original Wuhan strain virus (Kim et al., 2022c). Therefore, ACE2 exemplifies a ‘meet change with constancy’ target for COVID‐19 drug discovery in that, unlike ever‐mutating SARS‐CoV‐2 (Desai et al., 2021; Obeng et al., 2022), ACE2 in the host is unlikely to mutate.…”

Section: Defence: Evs As a Nanodecoy To Defend Against Sars‐cov‐2 Col...mentioning

confidence: 99%

“…Notably, although the strategy mentioned above has shown some positive results, EVs as a ‘weapon’ for virus defence still leave numerous issues to be considered: (1) Comprehensive blocking strategy (Obeng et al., 2022): EV nanodecoy therapy, which is one of the block approaches of entry for SARS‐CoV‐2, is expected to block cells with high ACE2 expression (Wang et al., 2021a). However, certain immune cell types such as macrophages can use endocytosis rather than ACE2‐dependent methods to take up the SARS‐CoV‐2 virus (Wang et al., 2021a).…”

Section: Defence: Evs As a Nanodecoy To Defend Against Sars‐cov‐2 Col...mentioning

confidence: 99%

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Meet changes with constancy: Defence, antagonism, recovery, and immunity roles of extracellular vesicles in confronting SARS‐CoV‐2

Chen

Song

et al. 2022

J of Extracellular Vesicle

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Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has wrought havoc on the world economy and people's daily lives. The inability to comprehensively control COVID‐19 is due to the difficulty of early and timely diagnosis, the lack of effective therapeutic drugs, and the limited effectiveness of vaccines. The body contains billions of extracellular vesicles (EVs), which have shown remarkable potential in disease diagnosis, drug development, and vaccine carriers. Recently, increasing evidence has indicated that EVs may participate or assist the body in defence, antagonism, recovery and acquired immunity against SARS‐CoV‐2. On the one hand, intercepting and decrypting the general intelligence carried in circulating EVs from COVID‐19 patients will provide an important hint for diagnosis and treatment; on the other hand, engineered EVs modified by gene editing in the laboratory will amplify the effectiveness of inhibiting infection, replication and destruction of ever‐mutating SARS‐CoV‐2, facilitating tissue repair and making a better vaccine. To comprehensively understand the interaction between EVs and SARS‐CoV‐2, providing new insights to overcome some difficulties in the diagnosis, prevention and treatment of COVID‐19, we conducted a rounded review in this area. We also explain numerous critical challenges that these tactics face before they enter the clinic, and this work will provide previous ‘meet change with constancy’ lessons for responding to future similar public health disasters. Extracellular vesicles (EVs) provide a ‘meet changes with constancy’ strategy to combat SARS‐CoV‐2 that spans defence, antagonism, recovery, and acquired immunity. Targets for COVID‐19 diagnosis, therapy, and prevention of progression may be found by capture of the message decoding in circulating EVs. Engineered and biomimetic EVs can boost effects of the natural EVs, especially anti‐SARS‐CoV‐2, targeted repair of damaged tissue, and improvement of vaccine efficacy.

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Section:  Defence: Evs As a Nanodecoy To Defend Against Sars-cov- C...mentioning

confidence: 99%

Section: Defence: Evs As a Nanodecoy To Defend Against Sars‐cov‐2 Col...mentioning

confidence: 99%

Section: Defence: Evs As a Nanodecoy To Defend Against Sars‐cov‐2 Col...mentioning

confidence: 99%

See 1 more Smart Citation

Meet changes with constancy: Defence, antagonism, recovery, and immunity roles of extracellular vesicles in confronting SARS‐CoV‐2

Chen

Song

et al. 2022

J of Extracellular Vesicle

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“…An orthogonal approach to antibodies employs soluble forms of the viral receptor, the angiotensin-converting enzyme 2 (ACE2), that can be used to "trap" and neutralize all coronaviruses that use ACE2 as a primary receptor [6][7][8] . To increase avidity, different fusion partners of ACE2 have been employed, including the Fc parts of IgG antibodies or oligomerization motifs 6,[9][10][11][12] . As multi-valent binders seemed most promising, we exploited the potential of the oligomerization motif leading to the highest avidity in the immune system, the Fc segment of IgM 12 .…”

mentioning

confidence: 99%

“…To increase avidity, different fusion partners of ACE2 have been employed, including the Fc parts of IgG antibodies or oligomerization motifs 6,[9][10][11][12] . As multi-valent binders seemed most promising, we exploited the potential of the oligomerization motif leading to the highest avidity in the immune system, the Fc segment of IgM 12 . It has been reported that reformatting virus-specific IgGs into IgM antibodies can lead to an enhancement in neutralization efficiency against SARS-CoV-2 13 .…”

mentioning

confidence: 99%

Multimeric ACE2-IgM fusions as broadly active antivirals that potently neutralize SARS-CoV-2 variants

et al. 2022

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Coronavirus infections are a world-wide threat to human health. A promising strategy to develop a broadly active antiviral is the use of fusion proteins consisting of an antibody IgG Fc region and a human ACE2 domain to which the viral spike proteins bind. Here we create antiviral fusion proteins based on IgM scaffolds. The hexameric ACE2-IgM-Fc fusions can be efficiently produced in mammalian cells and they neutralize the infectious virus with picomolar affinity thus surpassing monomeric ACE2-IgM-Fc by up to 96-fold in potency. In addition, the ACE2-IgM fusion shows increased neutralization efficiency for the highly infectious SARS-CoV-2 omicron variant in comparison to prototypic SARS-CoV-2. Taken together, these multimeric IgM fusions proteins are a powerful weapon to fight coronavirus infections.

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A Review of Extracellular Vesicles in COVID‐19 Diagnosis, Treatment, and Prevention

Xie

et al. 2023

Advanced Science

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The 2019 novel coronavirus disease (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is ongoing, and has necessitated scientific efforts in disease diagnosis, treatment, and prevention. Interestingly, extracellular vesicles (EVs) have been crucial in these developments. EVs are a collection of various nanovesicles which are delimited by a lipid bilayer. They are enriched in proteins, nucleic acids, lipids, and metabolites, and naturally released from different cells. Their natural material transport properties, inherent long‐term recycling ability, excellent biocompatibility, editable targeting, and inheritance of parental cell properties make EVs one of the most promising next‐generation drug delivery nanocarriers and active biologics. During the COVID‐19 pandemic, many efforts have been made to exploit the payload of natural EVs for the treatment of COVID‐19. Furthermore, strategies that use engineered EVs to manufacture vaccines and neutralization traps have produced excellent efficacy in animal experiments and clinical trials. Here, the recent literature on the application of EVs in COVID‐19 diagnosis, treatment, damage repair, and prevention is reviewed. And the therapeutic value, application strategies, safety, and biotoxicity in the production and clinical applications of EV agents for COVID‐19 treatment, as well as inspiration for using EVs to block and eliminate novel viruses are discussed.

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Multivalent ACE2 engineering—A promising pathway for advanced coronavirus nanomedicine development

Cited by 8 publications

References 256 publications

Meet changes with constancy: Defence, antagonism, recovery, and immunity roles of extracellular vesicles in confronting SARS‐CoV‐2

Meet changes with constancy: Defence, antagonism, recovery, and immunity roles of extracellular vesicles in confronting SARS‐CoV‐2

Multimeric ACE2-IgM fusions as broadly active antivirals that potently neutralize SARS-CoV-2 variants

A Review of Extracellular Vesicles in COVID‐19 Diagnosis, Treatment, and Prevention

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