Viral Envelope Membrane: A Special Entry Pathway and a Promising Drug Target

2021 ◽  
Vol 28 ◽  
Author(s):  
Nastasja Palombi ◽  
Annalaura Brai ◽  
Martina Gerace ◽  
Salvatore Di Maria ◽  
Francesco Orofino ◽  
...  
Keyword(s):  
Drug Target ◽  
Viral Infections ◽  
Viral Envelope ◽  
Envelope Membrane ◽  
Virus Infections ◽  
Enveloped Viruses ◽  
Enveloped Virus ◽  
Entry Pathway ◽  
Current Century ◽  
Spanish Flu

Abstract: Enveloped viruses belong to a large class of pathogens responsible for multiple serious diseases. Their spread into new territories has been the cause of major epidemics throughout human history, including the Spanish flu in 1918 and the latest COVID-19 pandemic. Thanks to their outer membrane, consisting essentially of host lipids, enveloped viruses are more resistant to enzymes, and are also less susceptible to host immune defenses than their naked counterparts. Therefore, the development of effective approaches to combat enveloped virus infections represents a major challenge for antiviral therapy in the current century. This review focuses on the characteristics of enveloped viruses, their importance in the entry phase, drugs targeting envelope membrane-mediated entry, and those specifically designed to target the envelope. The broad-spectrum antiviral activity of these compounds can be attributed to their ability to affect the envelope, an essential structural feature common to several viruses. This makes this class of compounds agents of great interest when no specific drugs or vaccines are available to block viral infections.

scholarly journals Exploring lectin–glycan interactions to combat COVID-19: Lessons acquired from other enveloped viruses

Glycobiology ◽  
2020 ◽  
Author(s):  
Luís Cláudio Nascimento da Silva ◽  
Juliana Silva Pereira Mendonça ◽  
Weslley Felix de Oliveira ◽  
Karla Lílian Rodrigues Batista ◽  
Adrielle Zagmignan ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Whole Blood ◽  
Therapeutic Approach ◽  
Viral Infections ◽  
Viral Envelope ◽  
Structural Studies ◽  
Human Coronavirus ◽  
Enveloped Viruses ◽  
Wide Range ◽  
Great Pressure

Abstract The emergence of a new human coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed great pressure on the health system worldwide. The presence of glycoproteins on the viral envelope opens a wide range of possibilities for the application of lectins to address some urgent problems involved in this pandemic. In this work, we discuss the potential contributions of lectins from nonmammalian sources in the development of several fields associated with viral infections, most notably COVID-19. We review the literature on the use of nonmammalian lectins as a therapeutic approach against members of the Coronaviridae family, including recent advances in strategies of protein engineering to improve their efficacy. The applications of lectins as adjuvants for antiviral vaccines are also discussed. Finally, we present some emerging strategies employing lectins for the development of biosensors, microarrays, immunoassays and tools for purification of viruses from whole blood. Altogether, the data compiled in this review highlight the importance of structural studies aiming to improve our knowledge about the basis of glycan recognition by lectins and its repercussions in several fields, providing potential solutions for complex aspects that are emerging from different health challenges.

scholarly journals Mechanisms of Methods for Hepatitis C Virus Inactivation

2014 ◽  
Vol 81 (5) ◽  
pp. 1616-1621 ◽  
Author(s):  
Stephanie Pfaender ◽  
Janine Brinkmann ◽  
Daniel Todt ◽  
Nina Riebesehl ◽  
Joerg Steinmann ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Infection Control ◽  
Viral Envelope ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virus Inactivation ◽  
Protection Assay ◽  
Uv Treatment ◽  
Enveloped Viruses ◽  
Enveloped Virus

ABSTRACTVirus inactivation by chemical disinfectants is an important instrument for infection control in medical settings, but the mechanisms involved are poorly understood. In this study, we systematically investigated the effects of several antiviral treatments on hepatitis C virus (HCV) particles as model for enveloped viruses. Studies were performed with authentic cell culture-derived viruses, and the influence of chemical disinfectants, heat, and UV treatment on HCV was analyzed by the determination of infectious particles in a limiting-dilution assay, by quantitative reverse transcription-PCR, by core enzyme-linked immunosorbent assay, and by proteolytic protection assay. All different inactivation methods resulted in a loss of HCV infectivity by targeting different parts of the virus particle. Alcohols such as ethanol and 2-propanol did not affect the viral RNA genome integrity but disrupted the viral envelope membrane in a capsid protection assay. Heat and UV treatment of HCV particles resulted in direct damage of the viral genome since transfection of viral particle-associated RNA into permissive cells did not initiate RNA replication. In addition, heat incubation at 80°C disrupted the HCV envelope, rendering the viral capsid susceptible to proteolytic digest. This study demonstrated the molecular processes of viral inactivation of an enveloped virus and should facilitate the development of effective disinfection strategies in infection control not only against HCV but also against other enveloped viruses.

scholarly journals How Do Enveloped Viruses Exploit the Secretory Proprotein Convertases to Regulate Infectivity and Spread?

2021 ◽  
Author(s):  
Nabil G Seidah ◽  
Antonella Pasquato ◽  
Ursula Andreo
Keyword(s):  
Plasma Membranes ◽  
Viral Infections ◽  
Limited Proteolysis ◽  
Viral Envelope ◽  
Host Cells ◽  
Surface Glycoprotein ◽  
Type I ◽  
Proprotein Convertases ◽  
Enveloped Viruses ◽  
Surface Glycoproteins

Inhibition of the binding of enveloped viruses surface glycoproteins to host cell receptor(s) is a major target of vaccines and constitutes an efficient strategy to block viral entry and infection of various host cells and tissues. Cellular entry usually requires fusion of the viral envelope with host plasma membranes. Such entry mechanism is often preceded by “priming” and/or “activation” steps requiring limited proteolysis of the viral surface glycoprotein to expose a fusiogenic domain for efficient membrane juxtapositions. The 9-membered family of Proprotein Convertases related to Subtilisin/Kexin (PCSK) serine proteases (PC1, PC2, Furin, PC4, PC5, PACE4, PC7, SKI-1/S1P and PCSK9) participate in post-translational cleavages and/or regulation of multiple secretory proteins. The type-I membrane-bound Furin and SKI-1/S1P are the major convertases responsible for the processing of surface glycoproteins of enveloped viruses. Stefan Kunz has considerably contributed to define the role of SKI-1/S1P in the activation of arenaviruses causing hemorrhagic fever. Furin was recently implicated in the activation of the spike S-protein of SARS-CoV-2 and Furin-inhibitors are being tested as antivirals in COVID-19. Other members of the PCSK-family are also implicated in some viral infections such as PCSK9 in Dengue. Herein, we summarize the various functions of the PCSKs and present arguments whereby their inhibition could represent a powerful arsenal to limit viral infections causing the present and future pandemics.

scholarly journals Afucosylated immunoglobulin G responses are a hallmark of enveloped virus infections and show an exacerbated phenotype in COVID-19

2020 ◽  
Author(s):  
Mads Delbo Larsen ◽  
Erik L. de Graaf ◽  
Myrthe E. Sonneveld ◽  
H. Rosina Plomp ◽  
Federica Linty ◽  
...  
Keyword(s):  
Spike Protein ◽  
Igg Antibodies ◽  
Virus Infections ◽  
Protein Subunit ◽  
Enveloped Viruses ◽  
Enveloped Virus ◽  
Immune Mediated ◽  
Anti Cancer ◽  
Potential Factor ◽  
Attenuated Viruses

AbstractIgG antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc-tail, essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anti-cancer therapeutic antibodies for their elevated binding and killing activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG which are of minor abundance in humans (∼6% of total IgG) are specifically formed against surface epitopes of enveloped viruses after natural infections or immunization with attenuated viruses, while protein subunit immunization does not elicit this low fucose response. This can give beneficial strong responses, but can also go awry, resulting in a cytokine-storm and immune-mediated pathologies. In the case of COVID-19, the critically ill show aggravated afucosylated-IgG responses against the viral spike protein. In contrast, those clearing the infection unaided show higher fucosylation levels of the anti-spike protein IgG. Our findings indicate antibody glycosylation as a potential factor in inflammation and protection in enveloped virus infections including COVID-19.

scholarly journals How Do Enveloped Viruses Exploit the Secretory Proprotein Convertases to Regulate Infectivity and Spread?

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1229
Author(s):  
Nabil G. Seidah ◽  
Antonella Pasquato ◽  
Ursula Andréo
Keyword(s):  
Plasma Membranes ◽  
Viral Infections ◽  
Limited Proteolysis ◽  
Viral Envelope ◽  
Host Cells ◽  
Surface Glycoprotein ◽  
Type I ◽  
Proprotein Convertases ◽  
Enveloped Viruses ◽  
Surface Glycoproteins

Inhibition of the binding of enveloped viruses surface glycoproteins to host cell receptor(s) is a major target of vaccines and constitutes an efficient strategy to block viral entry and infection of various host cells and tissues. Cellular entry usually requires the fusion of the viral envelope with host plasma membranes. Such entry mechanism is often preceded by “priming” and/or “activation” steps requiring limited proteolysis of the viral surface glycoprotein to expose a fusogenic domain for efficient membrane juxtapositions. The 9-membered family of Proprotein Convertases related to Subtilisin/Kexin (PCSK) serine proteases (PC1, PC2, Furin, PC4, PC5, PACE4, PC7, SKI-1/S1P, and PCSK9) participate in post-translational cleavages and/or regulation of multiple secretory proteins. The type-I membrane-bound Furin and SKI-1/S1P are the major convertases responsible for the processing of surface glycoproteins of enveloped viruses. Stefan Kunz has considerably contributed to define the role of SKI-1/S1P in the activation of arenaviruses causing hemorrhagic fever. Furin was recently implicated in the activation of the spike S-protein of SARS-CoV-2 and Furin-inhibitors are being tested as antivirals in COVID-19. Other members of the PCSK-family are also implicated in some viral infections, such as PCSK9 in Dengue. Herein, we summarize the various functions of the PCSKs and present arguments whereby their inhibition could represent a powerful arsenal to limit viral infections causing the present and future pandemics.

scholarly journals THERAPEUTIC APPLICATIONS OF Spirulina AGAINST HUMAN PATHOGENIC VIRUSES

2021 ◽  
Vol 9 (Spl-1- GCSGD_2020) ◽  
pp. S38-S42
Author(s):  
Sharolynne Xiao Tong Liang ◽  
◽  
Ling Shing Wong ◽  
Anto Cordelia Tanislaus Antony Dhanapal ◽  
Prakash Balu ◽  
...  
Keyword(s):  
Measles Virus ◽  
Therapeutic Agent ◽  
Viral Infections ◽  
Emerging Infectious Diseases ◽  
Antiviral Effect ◽  
Food Supplement ◽  
Host Cells ◽  
Swine Flu ◽  
Virus Infections ◽  
Enveloped Viruses

Viruses can spread worldwide and the early detection of emerging infectious diseases and outbreaks in humans and animals is important for effective surveillance and prevention. Viruses such as human immunodeficiency virus (HIV), swine flu, and influenza virus are some of the viruses that spread diseases worldwide. However, the non-availability of effective antiviral drugs and the drug-resistance among the virus and host have become the major problems in controlling viral infections. The natural products from microalgae can be an alternative therapeutic agent to control viral infections in humans. Spirulina is a well-known cyanobacterium that has been consumed by humans as a food supplement for more than centuries without side-effects. Spirulina possesses high nutritional values and provides numerous health benefits to the consumers. Spirulina can be an alternative natural therapeutic agent for numerous virus infections as it contains several bioactive compounds with proven antiviral effect on enveloped viruses (Herpes simplex virus, measles virus, mumps virus) and non-enveloped viruses (astrovirus, rotavirus) by preventing the spread of the virus in the host cells. Spirulina also serves as a natural supplement that strengthens the immune system. This review focuses on the antiviral properties and immunostimulant effects of Spirulina as a potential therapeutic supplement on human health.

scholarly journals A Broad-Spectrum Antiviral Peptide Blocks Infection of Viruses by Binding to Phosphatidylserine in the Viral Envelope

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1989 ◽  
Author(s):  
Rutger D. Luteijn ◽  
Patrique Praest ◽  
Frank Thiele ◽  
Saravanan Manikam Sadasivam ◽  
Katrin Singethan ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Rift Valley Fever Virus ◽  
Antiviral Drug ◽  
Viral Envelope ◽  
Virus Protein ◽  
Cowpox Virus ◽  
Virus Infections ◽  
Anionic Phospholipid ◽  
Enveloped Viruses ◽  
Antiviral Peptide

The ongoing threat of viral infections and the emergence of antiviral drug resistance warrants a ceaseless search for new antiviral compounds. Broadly-inhibiting compounds that act on elements shared by many viruses are promising antiviral candidates. Here, we identify a peptide derived from the cowpox virus protein CPXV012 as a broad-spectrum antiviral peptide. We found that CPXV012 peptide hampers infection by a multitude of clinically and economically important enveloped viruses, including poxviruses, herpes simplex virus-1, hepatitis B virus, HIV-1, and Rift Valley fever virus. Infections with non-enveloped viruses such as Coxsackie B3 virus and adenovirus are not affected. The results furthermore suggest that viral particles are neutralized by direct interactions with CPXV012 peptide and that this cationic peptide may specifically bind to and disrupt membranes composed of the anionic phospholipid phosphatidylserine, an important component of many viral membranes. The combined results strongly suggest that CPXV012 peptide inhibits virus infections by direct interactions with phosphatidylserine in the viral envelope. These results reiterate the potential of cationic peptides as broadly-acting virus inhibitors.

Therapeutic Exploitation of Viral Interference

2020 ◽  
Vol 20 (4) ◽  
pp. 423-432 ◽  
Author(s):  
Imre Kovesdi ◽  
Tibor Bakacs
Keyword(s):  
Broad Spectrum ◽  
Viral Infections ◽  
Viral Vector ◽  
Antiviral Treatment ◽  
Type I ◽  
Virus Infections ◽  
Emerging Viruses ◽  
Viral Interference ◽  
Pathogenic Virus ◽  
Hepatitis C Rna

: Viral interference, originally, referred to a state of temporary immunity, is a state whereby infection with a virus limits replication or production of a second infecting virus. However, replication of a second virus could also be dominant over the first virus. In fact, dominance can alternate between the two viruses. Expression of type I interferon genes is many times upregulated in infected epithelial cells. Since the interferon system can control most, if not all, virus infections in the absence of adaptive immunity, it was proposed that viral induction of a nonspecific localized temporary state of immunity may provide a strategy to control viral infections. Clinical observations also support such a theory, which gave credence to the development of superinfection therapy (SIT). SIT is an innovative therapeutic approach where a non-pathogenic virus is used to infect patients harboring a pathogenic virus. : For the functional cure of persistent viral infections and for the development of broad- spectrum antivirals against emerging viruses a paradigm shift was recently proposed. Instead of the virus, the therapy should be directed at the host. Such a host-directed-therapy (HDT) strategy could be the activation of endogenous innate immune response via toll-like receptors (TLRs). Superinfection therapy is such a host-directed-therapy, which has been validated in patients infected with two completely different viruses, the hepatitis B (DNA), and hepatitis C (RNA) viruses. SIT exerts post-infection interference via the constant presence of an attenuated non-pathogenic avian double- stranded (ds) RNA viral vector which boosts the endogenous innate (IFN) response. SIT could, therefore, be developed into a biological platform for a new “one drug, multiple bugs” broad-spectrum antiviral treatment approach.

scholarly journals Innate Immunity in Children and the Role of ACE2 Expression in SARS-CoV-2 Infection

2021 ◽  
Vol 13 (3) ◽  
pp. 363-382
Author(s):  
Mario Dioguardi ◽  
Angela Pia Cazzolla ◽  
Claudia Arena ◽  
Diego Sovereto ◽  
Giorgia Apollonia Caloro ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Viral Disease ◽  
Receptor Expression ◽  
Virus Infections ◽  
Search Terms ◽  
Bibliographic Search ◽  
Meta Analyses

COVID-19 (Coronavirus Disease 2019) is an emerging viral disease caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which leads to severe respiratory infections in humans. The first reports came in December 2019 from the city of Wuhan in the province of Hubei in China. It was immediately clear that children developed a milder disease than adults. The reasons for the milder course of the disease were attributed to several factors: innate immunity, difference in ACE2 (angiotensin-converting enzyme II) receptor expression, and previous infections with other common coronaviruses (CovH). This literature review aims to summarize aspects of innate immunity by focusing on the role of ACE2 expression and viral infections in children in modulating the antibody response to SARS-CoV-2 infection. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles deemed potentially eligible were considered, including those dealing with COVID-19 in children and providing more up-to-date and significant data in terms of epidemiology, prognosis, course, and symptoms, focusing on the etiopathogenesis of SARS-CoV-2 disease in children. The bibliographic search was conducted using the search engines PubMed and Scopus. The following search terms were entered in PubMed and Scopus: COVID-19 AND ACE2 AND Children; COVID-19 AND Immunity innate AND children. The search identified 857 records, and 18 studies were applicable based on inclusion and exclusion criteria that addressed the issues of COVID-19 concerning the role of ACE2 expression in children. The scientific literature agrees that children develop milder COVID-19 disease than adults. Milder symptomatology could be attributed to innate immunity or previous CovH virus infections, while it is not yet fully understood how the differential expression of ACE2 in children could contribute to milder disease.

scholarly journals Virus infections of honeybees Apis Mellifera

2015 ◽  
Vol 4 (3) ◽  
Author(s):  
Giuseppina Tantillo ◽  
Marilisa Bottaro ◽  
Angela Di Pinto ◽  
Vito Martella ◽  
Pietro Di Pinto ◽  
...  
Keyword(s):  
Viral Infections ◽  
Control Strategies ◽  
Future Research ◽  
Virus Infections ◽  
Deformed Wing Virus ◽  
Starting Point ◽  
Invasive Organisms ◽  
Queen Cell ◽  
Kashmir Bee Virus ◽  
Paralysis Virus

The health and vigour of honeybee colonies are threatened by numerous parasites (such as <em>Varroa destructor</em> and <em>Nosema</em> spp.) and pathogens, including viruses, bacteria, protozoa. Among honeybee pathogens, viruses are one of the major threats to the health and wellbeing of honeybees and cause serious concern for researchers and beekeepers. To tone down the threats posed by these invasive organisms, a better understanding of bee viral infections will be of crucial importance in developing effective and environmentally benign disease control strategies. Here we summarize recent progress in the understanding of the morphology, genome organization, transmission, epidemiology and pathogenesis of eight honeybee viruses: Deformed wing virus (DWV) and Kakugo virus (KV); Sacbrood virus (SBV); Black Queen cell virus (BQCV); Acute bee paralysis virus (ABPV); Kashmir bee virus (KBV); Israeli Acute Paralysis Virus (IAPV); Chronic bee paralysis virus (CBPV). The review has been designed to provide researchers in the field with updated information about honeybee viruses and to serve as a starting point for future research.

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