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.

scholarly journals Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses

2020 ◽  
Author(s):  
Xi Yu ◽  
Liming Zhang ◽  
Liangqin Tong ◽  
Nana Zhang ◽  
Han Wang ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Lipase Activity ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Viral Envelope ◽  
Global Public Health ◽  
Virucidal Activity ◽  
Extracellular Milieu

AbstractViruses are the major aetiological agents of acute and chronic severe human diseases that place a tremendous burden on global public health and economy; however, for most viruses, effective prophylactics and therapeutics are lacking, in particular, broad-spectrum antiviral agents. Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation of CbAE-1 in its lipase motif fully abrogated the virucidal ability. Furthermore, CbAE-2 presented low toxicity in vivo and in vitro, highlighting its potential as a broad-spectrum antiviral drug.

scholarly journals Role of Remdesivir in COVID-19

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Sumera Shaeen ◽  
◽  
Naila Abdul Sattar ◽  
Mohammad Ibrahim ◽  
Muhammad Irfan ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Infectious Diseases ◽  
Rna Polymerase ◽  
Broad Spectrum ◽  
Common Cold ◽  
Rna Virus ◽  
Antiviral Drug ◽  
Virus Infections ◽  
Polymerase Inhibitor

Remdesivir is an antiviral drug showed broad spectrum against viruses, also RNA polymerase inhibitor that’s why use to treat a variety of RNA virus infections. It is considered to be more effective against family of respiratory infection causing viruses including corona virus as compared to those whom it was originally synthesized like Hepatitis C and common cold viruses. On October 8, 2020, The National Institute of Allergy and Infectious Diseases has completed trials on COVID-19 patients and found Remdesivir satisfactory and beneficiary choice towards the recovery stairs of COVID-19. The pandemic of Covid-19 might wean down by season, but the possibility of reoccurrence exists. Thus, future clearance of Remdesivir might be critical for ensuring effective treatment, diminish mortality and permit early release.

scholarly journals Broad-Spectrum Antiviral Entry Inhibition by Interfacially Active Peptides

2020 ◽  
Vol 94 (23) ◽  
Author(s):  
Andrew R. Hoffmann ◽  
Shantanu Guha ◽  
Eric Wu ◽  
Jenisha Ghimire ◽  
Yilin Wang ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
Mammalian Cells ◽  
Viral Disease ◽  
Antiviral Drugs ◽  
Viral Envelope ◽  
Molecular Characteristics ◽  
Enveloped Viruses ◽  
Interfacial Activity ◽  
Active Peptides

ABSTRACT Numerous peptides inhibit the entry of enveloped viruses into cells. Some of these peptides have been shown to inhibit multiple unrelated viruses. We have suggested that such broad-spectrum antiviral peptides share a property called interfacial activity; they are somewhat hydrophobic and amphipathic, with a propensity to interact with the interfacial zones of lipid bilayer membranes. In this study, we further tested the hypothesis that such interfacial activity is a correlate of broad-spectrum antiviral activity. In this study, several families of peptides, selected for the ability to partition into and disrupt membrane integrity but with no known antiviral activity, were tested for the ability to inhibit multiple diverse enveloped viruses. These include Lassa pseudovirus, influenza virus, dengue virus type 2, herpes simplex virus 1, and nonenveloped human adenovirus 5. Various families of interfacially active peptides caused potent inhibition of all enveloped viruses tested at low and submicromolar concentrations, well below the range in which they are toxic to mammalian cells. These membrane-active peptides block uptake and fusion with the host cell by rapidly and directly interacting with virions, destabilizing the viral envelope, and driving virus aggregation and/or intervirion envelope fusion. We speculate that the molecular characteristics shared by these peptides can be exploited to enable the design, optimization, or molecular evolution of novel broad-spectrum antiviral therapeutics. IMPORTANCE New classes of antiviral drugs are needed to treat the ever-changing viral disease landscape. Current antiviral drugs treat only a small number of viral diseases, leaving many patients with established or emerging infections to be treated solely with supportive care. Recent antiviral peptide research has produced numerous membrane-interacting peptides that inhibit diverse enveloped viruses in vitro and in vivo. Peptide therapeutics are becoming more common, with over 60 FDA-approved peptides for clinical use. Included in this class of therapeutics is enfuvirtide, a 36-residue peptide drug that inhibits HIV entry/fusion. Due to their broad-spectrum mechanism of action and enormous potential sequence diversity, peptides that inhibit virus entry could potentially fulfill the need for new antiviral therapeutics; however, a better understanding of their mechanism is needed for the optimization or evolution of sequence design to combat the wide landscape of viral disease.

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.

Design, Synthesis, and Pharmacokinetic Evaluation of O-Carbamoyl Tizoxanide Prodrugs

2020 ◽  
Vol 16 ◽  
Author(s):  
Xi He ◽  
Wenjun Hu ◽  
Fanhua Meng ◽  
Xingzhou Li
Keyword(s):  
Plasma Concentration ◽  
Broad Spectrum ◽  
Plasma Concentrations ◽  
Antiviral Drug ◽  
Systemic Exposure ◽  
Pharmacokinetic Profile ◽  
Hydroxyl Group ◽  
First Pass

Background: The broad-spectrum antiparasitic drug nitazoxanide (N) has been repositioned as a broad-spectrum antiviral drug. Nitazoxanide’s in vivo antiviral activities are mainly attributed to its metabolitetizoxanide, the deacetylation product of nitazoxanide. In reference to the pharmacokinetic profile of nitazoxanide, we proposed the hypotheses that the low plasma concentrations and the low system exposure of tizoxanide after dosing with nitazoxanide result from significant first pass effects in the liver. It was thought that this may be due to the unstable acyloxy bond of nitazoxanide. Objective: Tizoxanide prodrugs, with the more stable formamyl substituent attached to the hydroxyl group rather than the acetyl group of nitazoxanide, were designed with the thought that they might be more stable in plasma. It was anticipated that these prodrugs might be less affected by the first pass effect, which would improve plasma concentrations and system exposure of tizoxanide. Method: These O-carbamoyl tizoxanide prodrugs were synthesized and evaluated in a mouse model for pharmacokinetic (PK) properties and in an in vitro model for plasma stabilities. Results: The results indicated that the plasma concentration and the systemic exposure of tizoxanide (T) after oral administration of O-carbamoyl tizoxanide prodrugs were much greater than that produced by equimolar dosage of nitazoxanide. It was also found that the plasma concentration and the systemic exposure of tizoxanide glucuronide (TG) were much lower than that produced by nitazoxanide. Conclusion: Further analysis showed that the suitable plasma stability of O-carbamoyl tizoxanide prodrugs is the key factor in maximizing the plasma concentration and the systemic exposure of the active ingredient tizoxanide.

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 Native Structure-Based Peptides as Potential Protein–Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2157
Author(s):  
Norbert Odolczyk ◽  
Ewa Marzec ◽  
Maria Winiewska-Szajewska ◽  
Jarosław Poznański ◽  
Piotr Zielenkiewicz
Keyword(s):  
Drug Development ◽  
Protein Interactions ◽  
Rna Virus ◽  
Antiviral Drug ◽  
Host Protein ◽  
Host Cells ◽  
Cell Surface Receptor ◽  
Short Peptides ◽  
Virus Protein ◽  
Positive Strand Rna

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a positive-strand RNA virus that causes severe respiratory syndrome in humans, which is now referred to as coronavirus disease 2019 (COVID-19). Since December 2019, the new pathogen has rapidly spread globally, with over 65 million cases reported to the beginning of December 2020, including over 1.5 million deaths. Unfortunately, currently, there is no specific and effective treatment for COVID-19. As SARS-CoV-2 relies on its spike proteins (S) to bind to a host cell-surface receptor angiotensin-converting enzyme-2(ACE2), and this interaction is proved to be responsible for entering a virus into host cells, it makes an ideal target for antiviral drug development. In this work, we design three very short peptides based on the ACE2 sequence/structure fragments, which may effectively bind to the receptor-binding domain (RBD) of S protein and may, in turn, disrupt the important virus-host protein–protein interactions, blocking early steps of SARS-CoV-2 infection. Two of our peptides bind to virus protein with affinity in nanomolar range, and as very short peptides have great potential for drug development.

Rift Valley fever virus infections in Egyptian cattle and their prevention

2017 ◽  
Vol 64 (6) ◽  
pp. 2049-2058 ◽  
Author(s):  
C. Mroz ◽  
M. Gwida ◽  
M. El-Ashker ◽  
U. Ziegler ◽  
T. Homeier-Bachmann ◽  
...  
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Virus Infections ◽  
Valley Fever

Antiviral Therapy of Haemorrhagic Fevers and Arbovirus Infections

1998 ◽  
Vol 3 (2) ◽  
pp. 53-79
Author(s):  
Mike Bray ◽  
John Huggins
Keyword(s):  
New World ◽  
Protective Efficacy ◽  
Rift Valley Fever Virus ◽  
Antiviral Drug ◽  
Drug Effects ◽  
Lassa Fever ◽  
Interferon Α ◽  
Haemorrhagic Fever ◽  
Valley Fever

RNA viruses of the families Arena-, Bunya-, Filo-, Flavi-and Togaviridae cause illness in humans ranging from mild, non-specific febrile syndromes to fulminant, lethal haemorrhagic fever. They are transmitted from animals to humans and from human to human by arthropods, aerosols or contact with body fluids. Antiviral compounds, convalescent plasma and interferon inhibit many of these agents in vitro and in virus-infected animals. Drug or plasma treatment is now in use for several human diseases, and would probably be beneficial for a number of others for which there is only limited treatment experience. Success is linked to early diagnosis and initiation of therapy. Ribavirin is used to treat Lassa fever and haemorrhagic fever with renal syndrome, and would probably be effective for Crimean-Congo haemorrhagic fever and for all New World arenavirus diseases. The value of ribavirin in the early treatment of hantavirus pulmonary syndrome is under evaluation. Convalescent plasma is the therapy of choice for Argentine haemorrhagic fever, and would also probably be effective for other New World arenaviruses and some other infections if a safe supply of plasma could be maintained. Ribavirin and interferon-α have both shown protective efficacy in non-human primates infected with Rift Valley fever virus. No effective therapy has yet been identified for filovirus infections, but results in animal models are encouraging. More clinical research is urgently needed. Even if placebo-controlled drug trials cannot be performed, conscientious reports of the results of therapy in limited numbers of patients can still provide evidence of antiviral drug effects.

scholarly journals Nanodroplet-Benzalkonium Chloride Formulation Demonstrates In Vitro and Ex- Vivo Broad-Spectrum Antiviral Activity Against SARS-CoV-2 and other Enveloped Viruses

2021 ◽  
Author(s):  
Jessie Pannu ◽  
Susan Ciotti ◽  
Shyamala Ganesan ◽  
George Arida ◽  
Chad Costley ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
Benzalkonium Chloride ◽  
Ex Vivo ◽  
Viral Disease ◽  
Influenza B ◽  
Human Coronavirus ◽  
Enveloped Viruses ◽  
Nasal Irritation

Abstract Objective: The Covid-19 pandemic has highlighted the importance of aerosolized droplets inhaled into the nose in the transmission of respiratory viral disease. Inactivating pathogenic viruses at the nasal port of entry may reduce viral loads, thereby reducing infection, transmission and spread. In this communication, we demonstrate safe and broad anti-viral activity of oil-in-water nanoemulsion (nanodroplet) formulation containing the potent antiseptic 0.13% Benzalkonium Chloride (NE-BZK). Results: We have demonstrated that NE-BZK exhibits broad-spectrum, long-lasting antiviral activity with >99.9% in vitro killing of enveloped viruses including SARS-CoV-2, human coronavirus, RSV, and influenza B. In vitro and ex-vivo studies demonstrated continued killing of >99.99% of human coronavirus with diluted NE-BZK and persistent for 8 hours post application, respectively. The repeated application of NE-BZK, twice daily for 2 weeks into rabbit nostrils demonstrated its safety with no nasal irritation. These findings demonstrate that formulating BZK into the proprietary nanodroplets offers a safe and effective antiviral and a significant addition to strategies to combat the spread of respiratory viral infectious diseases.

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