Permanent Inhibition of Viral Entry by Covalent Entrapment of HIV gp41 on the Virus Surface

Biochemistry ◽  
2011 ◽  
Vol 50 (32) ◽  
pp. 6966-6972 ◽  
Author(s):  
Hyun Ah Yi ◽  
Barbara Diaz-Aguilar ◽  
Dominique Bridon ◽  
Omar Quraishi ◽  
Amy Jacobs
Keyword(s):  
Viral Entry ◽  
Virus Surface ◽  
Hiv Gp41

scholarly journals Neurological and Neuropsychological Changes Associated with SARS-CoV-2 Infection: New Observations, New Mechanisms

2021 ◽  
pp. 107385842098410
Author(s):  
Muhammad Ali Haidar ◽  
Hussam Jourdi ◽  
Zeinab Haj Hassan ◽  
Ohanes Ashekyan ◽  
Manal Fardoun ◽  
...  
Keyword(s):  
Viral Entry ◽  
Health Workers ◽  
The Elderly ◽  
Circumventricular Organs ◽  
Depression And Anxiety ◽  
Virus Surface ◽  
Angiotensin Converting Enzyme 2 ◽  
Neuropsychological Changes ◽  
High Risk Populations ◽  
The Central Nervous System

SARS-CoV-2 infects cells through angiotensin-converting enzyme 2 (ACE2), a ubiquitous receptor that interacts with the virus’ surface S glycoprotein. Recent reports show that the virus affects the central nervous system (CNS) with symptoms and complications that include dizziness, altered consciousness, encephalitis, and even stroke. These can immerge as indirect immune effects due to increased cytokine production or via direct viral entry into brain tissue. The latter is possible through neuronal access via the olfactory bulb, hematogenous access through immune cells or directly across the blood-brain barrier (BBB), and through the brain’s circumventricular organs characterized by their extensive and highly permeable capillaries. Last, the COVID-19 pandemic increases stress, depression, and anxiety within infected individuals, those in isolation, and high-risk populations like children, the elderly, and health workers. This review surveys the recent updates of CNS manifestations post SARS-CoV-2 infection along with possible mechanisms that lead to them.

scholarly journals Significance of thiol-disulfide balance in SARS-CoV-2 infection

2021 ◽  
Vol 72 (3) ◽  
pp. 30-36
Author(s):  
Tatjana Simić
Keyword(s):  
Cell Surface ◽  
Host Cell ◽  
Protein Interactions ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Alkylating Agents ◽  
Protein S ◽  
Protein Protein Interactions ◽  
Virus Surface ◽  
Host Cell Surface

Studies of the molecular mechanisms regarding interaction of different viruses with receptors on the host cell surface have shown that the viral entry depends on the specific relationship between free thiol (SH) groups and disulfides on the virus surface, as well as the thiol disulfide balance on the host cell surface. The presence of oxidizing compounds or alkylating agents, which disturb the thiol-disulfide balance on the surface of the virus, can also affect its infectious potential. Disturbed thiol-disulfide balance may also influence protein-protein interactions between SARS-CoV-2 protein S and ACE2 receptors of the host cell. This review presents the basic mechanisms of maintaining intracellular and extracellular thiol disulfide balance and previous experimental and clinical evidence in favor of impaired balance in SARS-CoV-2 infection. Besides, the results of the clinical application or experimental analysis of compounds that induce changes in the thiol disulfide balance towards reduction of disulfide bridges in proteins of interest in COVID-19 infection are presented.

scholarly journals Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry

2019 ◽  
Vol 94 (5) ◽  
Author(s):  
Yushun Wan ◽  
Jian Shang ◽  
Shihui Sun ◽  
Wanbo Tai ◽  
Jing Chen ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Cell Surface ◽  
Molecular Mechanism ◽  
Viral Entry ◽  
Fc Receptor ◽  
Spike Protein ◽  
Viral Receptor ◽  
Virus Surface ◽  
Proteolytic Activation ◽  
Antibody Dependent Enhancement

ABSTRACT Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies. IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.

scholarly journals Significant Differences in Cell–Cell Fusion and Viral Entry between Strains Revealed by Scanning Mutagenesis of the C-Heptad Repeat of HIV gp41

Biochemistry ◽  
2013 ◽  
Vol 52 (20) ◽  
pp. 3552-3563 ◽  
Author(s):  
Barbara Diaz-Aguilar ◽  
Karen DeWispelaere ◽  
Hyun Ah Yi ◽  
Amy Jacobs
Keyword(s):  
Cell Fusion ◽  
Viral Entry ◽  
Heptad Repeat ◽  
Cell Cell ◽  
Hiv Gp41

scholarly journals Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus

2015 ◽  
Vol 89 (17) ◽  
pp. 9119-9123 ◽  
Author(s):  
Yang Yang ◽  
Chang Liu ◽  
Lanying Du ◽  
Shibo Jiang ◽  
Zhengli Shi ◽  
...  
Keyword(s):  
Middle East ◽  
Viral Entry ◽  
Human Cells ◽  
Middle East Respiratory Syndrome ◽  
Intermediate Hosts ◽  
Virus Surface ◽  
Bat Coronavirus ◽  
Do So

To understand how Middle East respiratory syndrome coronavirus (MERS-CoV) transmitted from bats to humans, we compared the virus surface spikes of MERS-CoV and a related bat coronavirus, HKU4. Although HKU4 spike cannot mediate viral entry into human cells, two mutations enabled it to do so by allowing it to be activated by human proteases. These mutations are present in MERS-CoV spike, explaining why MERS-CoV infects human cells. These mutations therefore played critical roles in the bat-to-human transmission of MERS-CoV, either directly or through intermediate hosts.

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