Chemically Modified Human Serum Albumin Potently Blocks Entry of Ebola Pseudoviruses and Viruslike Particles

Li, Hao-Yang; Yu, Fei; Xia, Shuai; Yu, Yufeng; Wang, Qian; Liao, Ming; Wang, Yan; Jiang, Shibo; Lu, Lu

doi:10.1128/aac.02168-16

Cited by 20 publications

(19 citation statements)

References 54 publications

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“…Research on albumin has provided new insights such as the characterization of the pleiotropic effects of albumin (58). Conformational change to albumin can affect binding of viruses (59). The exact binding sites and therefore the interactions between protein FFA are unknown however the basic mechanism of competitive and non-competitive binding sites have been described.…”

Section: Human Serum Albuminmentioning

confidence: 99%

SARS-CoV-2 Bound Human Serum Albumin and Systemic Septic Shock

Johnson

Fatemi

Winlow

2020

Front. Cardiovasc. Med.

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The emergence of the COVID-19 virus and the subsequent pandemic have driven a great deal of research activity. The effects of COVID-19 are caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is the underlying actions of SARs-CoV-2 virions on the endothelial glycocalyx that we consider here. One of the key factors in COVID-19 infection is its almost unique age-related profile, with a doubling in mortality every 10 years after the age of 50. The endothelial glycocalyx layer is essential in maintaining normal fluid homeostasis, but is fragile and prone to pathophysiological damage. It is physiologically significant in capillary microcirculation and in fluid distribution to the tissues. Human serum albumin (HSA), the most abundant protein in plasma, is created in the liver which also maintains its concentration, but this reduces by 10-15% after 50 years of age. HSA transports hormones, free fatty acids and maintains oncotic pressure, but SARS-CoV-2 virions bind competitively to HSA diminishing its normal transport function. Furthermore, hypoalbuminemia is frequently observed in patients with such conditions as diabetes, hypertension, and chronic heart failure, i.e., those most vulnerable to SARS-CoV-2 infection. Hypoalbuminemia, coagulopathy, and vascular disease have been linked in COVID-19 and have been shown to predict outcome independent of age and morbidity. Hypoalbuminemia is also known factor in sepsis and Acute respiratory distress syndrome (ARDS) occurs when fluids build-up in the alveoli and it is associated with sepsis, whose mechanism is systemic, being associated with the fluid and logistic mechanisms of the circulation. Glycocalyx damage is associated with changes plasma protein concentration, particularly HSA and blockage of albumin transport can produce the systemic symptoms seen in SARS-CoV-2 infection and sepsis. We therefore conclude that albumin binding to SARS-CoV-2 virions may inhibit the formation of the endothelial glycocalyx by inhibition of albumin transport binding sites. We postulate that albumin therapy to replace bound albumin might alleviate some of the symptoms leading to sepsis and that clinical trials to test this postulation should be initiated as a matter of urgency.

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Section: Human Serum Albuminmentioning

confidence: 99%

SARS-CoV-2 Bound Human Serum Albumin and Systemic Septic Shock

Johnson

Fatemi

Winlow

2020

Front. Cardiovasc. Med.

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“…After incubation for 48 h, the culture medium was replaced by 100 μL of fresh cell medium with 4 μL of the solution from CCK-8. After incubation for an additional 2 h at 37 °C, the absorbance at 450 nm (A 450 ) was detected as the readout of cell viability [ 54 ].…”

Section: Methodsmentioning

confidence: 99%

Peptide-Based Membrane Fusion Inhibitors Targeting HCoV-229E Spike Protein HR1 and HR2 Domains

Xia

Wang

et al. 2018

IJMS

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Human coronavirus 229E (HCoV-229E) infection in infants, elderly people, and immunocompromised patients can cause severe disease, thus calling for the development of effective and safe therapeutics to treat it. Here we reported the design, synthesis and characterization of two peptide-based membrane fusion inhibitors targeting HCoV-229E spike protein heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains, 229E-HR1P and 229E-HR2P, respectively. We found that 229E-HR1P and 229E-HR2P could interact to form a stable six-helix bundle and inhibit HCoV-229E spike protein-mediated cell-cell fusion with IC50 of 5.7 and 0.3 µM, respectively. 229E-HR2P effectively inhibited pseudotyped and live HCoV-229E infection with IC50 of 0.5 and 1.7 µM, respectively. In a mouse model, 229E-HR2P administered intranasally could widely distribute in the upper and lower respiratory tracts and maintain its fusion-inhibitory activity. Therefore, 229E-HR2P is a promising candidate for further development as an antiviral agent for the treatment and prevention of HCoV-229E infection.

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“…Thus, this drug should be examined in clinical trials to be approved for the treatment of EVD ( 167 ). Chemically modified human serum albumin with 3-hydroxyphthalic anhydride (HP-HSA) has been demonstrated with the potential of a therapeutic candidate in resisting the EBOV infection ( 168 ).…”

Section: Advances In Developing Drugs and Therapies Against Ebovmentioning

confidence: 99%

Advances in Designing and Developing Vaccines, Drugs, and Therapies to Counter Ebola Virus

et al. 2018

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Ebola virus (EBOV), a member of the family Filoviridae, is responsible for causing Ebola virus disease (EVD) (formerly named Ebola hemorrhagic fever). This is a severe, often fatal illness with mortality rates varying from 50 to 90% in humans. Although the virus and associated disease has been recognized since 1976, it was only when the recent outbreak of EBOV in 2014–2016 highlighted the danger and global impact of this virus, necessitating the need for coming up with the effective vaccines and drugs to counter its pandemic threat. Albeit no commercial vaccine is available so far against EBOV, a few vaccine candidates are under evaluation and clinical trials to assess their prophylactic efficacy. These include recombinant viral vector (recombinant vesicular stomatitis virus vector, chimpanzee adenovirus type 3-vector, and modified vaccinia Ankara virus), Ebola virus-like particles, virus-like replicon particles, DNA, and plant-based vaccines. Due to improvement in the field of genomics and proteomics, epitope-targeted vaccines have gained top priority. Correspondingly, several therapies have also been developed, including immunoglobulins against specific viral structures small cell-penetrating antibody fragments that target intracellular EBOV proteins. Small interfering RNAs and oligomer-mediated inhibition have also been verified for EVD treatment. Other treatment options include viral entry inhibitors, transfusion of convalescent blood/serum, neutralizing antibodies, and gene expression inhibitors. Repurposed drugs, which have proven safety profiles, can be adapted after high-throughput screening for efficacy and potency for EVD treatment. Herbal and other natural products are also being explored for EVD treatment. Further studies to better understand the pathogenesis and antigenic structures of the virus can help in developing an effective vaccine and identifying appropriate antiviral targets. This review presents the recent advances in designing and developing vaccines, drugs, and therapies to counter the EBOV threat.

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Chemically Modified Human Serum Albumin Potently Blocks Entry of Ebola Pseudoviruses and Viruslike Particles

Cited by 20 publications

References 54 publications

SARS-CoV-2 Bound Human Serum Albumin and Systemic Septic Shock

SARS-CoV-2 Bound Human Serum Albumin and Systemic Septic Shock

Peptide-Based Membrane Fusion Inhibitors Targeting HCoV-229E Spike Protein HR1 and HR2 Domains

Advances in Designing and Developing Vaccines, Drugs, and Therapies to Counter Ebola Virus

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