scholarly journals Scorpion-Derived Antiviral Peptides with a Special Focus on Medically Important Viruses: An Update

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Moulay Abdelmonaim El Hidan ◽  
Mehdi Ait Laaradia ◽  
Omar El Hiba ◽  
Ahmed Draoui ◽  
Abdelmohcine Aimrane ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Infection ◽  
Bioactive Peptides ◽  
Biomedical Application ◽  
Scorpion Venom ◽  
Global Burden ◽  
Special Focus ◽  
Modes Of Action ◽  
Medical Issues ◽  
Antiviral Peptides

The global burden of viral infection, especially the current pandemics of SARS-CoV-2, HIV/AIDS, and hepatitis, is a very risky one. Additionally, HCV expresses the necessity for antiviral therapeutic elements. Venoms are known to contain an array of bioactive peptides that are commonly used in the treatment of various medical issues. Several peptides isolated from scorpion venom have recently been proven to possess an antiviral activity against several viral families. The aim of this review is to provide an up-to-date overview of scorpion antiviral peptides and to discuss their modes of action and potential biomedical application against different viruses.

scholarly journals Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Yize Li ◽  
Beihua Dong ◽  
Zuzhang Wei ◽  
Robert H. Silverman ◽  
Susan R. Weiss
Keyword(s):  
Antiviral Activity ◽  
Viral Replication ◽  
Viral Infection ◽  
Rna Viruses ◽  
Primary Response ◽  
Human Cells ◽  
Secondary Effect ◽  
Rnase L ◽  
Interferon Signaling ◽  
Highly Pathogenic

ABSTRACT Bats are reservoirs for many RNA viruses that are highly pathogenic in humans yet relatively apathogenic in the natural host. It has been suggested that differences in innate immunity are responsible. The antiviral OAS-RNase L pathway is well characterized in humans, but there is little known about its activation and antiviral activity in bats. During infection, OASs, upon sensing double-stranded RNA (dsRNA), produce 2′-5′ oligoadenylates (2-5A), leading to activation of RNase L which degrades viral and host RNA, limiting viral replication. Humans encode three active OASs (OAS1 to -3). Analysis of the Egyptian Rousette bat genome combined with mRNA sequencing from bat RoNi/7 cells revealed three homologous OAS proteins. Interferon alpha treatment or viral infection induced all three OAS mRNAs, but RNase L mRNA is constitutively expressed. Sindbis virus (SINV) or vaccinia virus (VACVΔE3L) infection of wild-type (WT) or OAS1-KO (knockout), OAS2-KO, or MAVS-KO RoNi/7 cells, but not RNase L-KO or OAS3-KO cells, induces robust RNase L activation. SINV replication is 100- to 200-fold higher in the absence of RNase L or OAS3 than in WT cells. However, MAVS-KO had no detectable effect on RNA degradation or replication. Thus, in RoNi/7 bat cells, as in human cells, activation of RNase L during infection and its antiviral activity are dependent primarily on OAS3 while MAVS signaling is not required for the activation of RNase L and restriction of infection. Our findings indicate that OAS proteins serve as pattern recognition receptors (PRRs) to recognize viral dsRNA and that this pathway is a primary response to virus rather than a secondary effect of interferon signaling. IMPORTANCE Many RNA viruses that are highly pathogenic in humans are relatively apathogenic in their bat reservoirs, making it important to compare innate immune responses in bats to those well characterized in humans. One such antiviral response is the OAS-RNase L pathway. OASs, upon sensing dsRNA, produce 2-5A, leading to activation of RNase L which degrades viral and host RNA, limiting viral replication. Analysis of Egyptian Rousette bat sequences revealed three OAS genes expressing OAS1, OAS2, and OAS3 proteins. Interferon treatment or viral infection induces all three bat OAS mRNAs. In these bat cells as in human cells, RNase L activation and its antiviral activity are dependent primarily on OAS3 while MAVS signaling is not required. Importantly, our findings indicate the OAS-RNase L system is a primary response to virus rather than a secondary effect of interferon signaling and therefore can be activated early in infection or while interferon signaling is antagonized.

scholarly journals Green Synthesized ZnO Nanoparticles Mediated by Mentha Spicata Extract Induce Plant Systemic Resistance against Tobacco Mosaic Virus

2020 ◽  
Vol 10 (15) ◽  
pp. 5054 ◽  
Author(s):  
Ahmed Abdelkhalek ◽  
Abdulaziz A. Al-Askar
Keyword(s):  
Antiviral Activity ◽  
Viral Infection ◽  
Tobacco Mosaic Virus ◽  
Green Synthesis ◽  
Mosaic Virus ◽  
Plant Pathogens ◽  
Systemic Resistance ◽  
Effective Control ◽  
Zno Nps ◽  
Mentha Spicata

Globally, plant viral infection is one of the most difficult challenges of food security, where considerable losses in crop production occur. Nanoparticles are an effective control agent against numerous plant pathogens. However, there is limited knowledge concerning their effects against viral infection. In the present study, the green synthesis of zinc oxide nanoparticles (ZnO NPs) using aqueous leaf extract of Mentha spicata was achieved. X-ray diffraction patterns confirmed the crystalline nature of the prepared ZnO NPs. Dynamic light scattering and scanning electron microscopy analyses revealed that the resultant ZnO NPs were spherical in shape with a particle size ranged from 11 to 88 nm. Fourier transmission infrared spectroscopy detected different functional groups, capping and stability agents, and showed Zn-O bond within wavenumber of 487 cm−1. Under greenhouse conditions, the antiviral activity of biological synthesized ZnO NPs (100 µg/mL) against Tobacco mosaic virus (TMV) was evaluated. The double foliar application of the prepared ZnO NPs, 24 h before and 24 h after TMV-inoculation, was the most effective treatment that showed a 90.21% reduction of viral accumulation level and disease severity. Additionally, the transcriptional levels of PAL, PR-1 (salicylic acid marker gene), CHS, and POD genes were induced and up-regulated in all ZnO NPs treated plants. Notably, the results exhibited that aqueous extract of Mentha spicata was an effective reducing agent for the green synthesis of ZnO NPs, which showed significant antiviral activity. Finally, the detected protective and curative activity of ZnO NPs against TMV can encourage us to recommend its application for plant viral disease management. To our knowledge, this is the first study describing the antiviral activity of the green synthesized ZnO NPs.

Single- and repeat-dose toxicity of IDX14184, a nucleotide prodrug with antiviral activity for hepatitis C viral infection, in mice, rats, and monkeys

2015 ◽  
Vol 35 (5) ◽  
pp. 472-490 ◽  
Author(s):  
S Luo ◽  
R Rush ◽  
D Standring
Keyword(s):  
Hepatitis C ◽  
Gastrointestinal Tract ◽  
Antiviral Activity ◽  
Viral Infection ◽  
Skeletal Muscles ◽  
Kidney Injury ◽  
Repeat Dose ◽  
Toxicity Profile ◽  
Lower Gastrointestinal Tract ◽  
Repeat Dose Toxicity

The single- and repeat-dose toxicity profile of IDX14184, a novel guanosine nucleotide prodrug with antiviral activity against hepatitis C viral infection, was characterized following once daily oral administration for durations up to 13, 26, and 32 weeks in mouse, rat, and cynomolgus monkey, respectively. The heart, liver, kidney, skeletal muscles, and lower gastrointestinal tract (cecum, colon, and/or rectum) were identified as the primary toxicity targets in these nonclinical species. The mouse was relatively insensitive to IDX14184-induced cardiac toxicity and hepatotoxicity. The rat was very sensitive to IDX14184-induced skeletal muscle, liver, heart, and lower gastrointestinal tract toxicity but relatively insensitive to kidney toxicity. The monkey is a good animal species to detect IDX14184-induced toxicity in the cardiac and skeletal muscles, and in the liver and kidney, but not lower gastrointestinal tract toxicity. The toxicity profile of IDX14184 was most appropriately characterized in rats and monkeys. The conduct of a series of cardiac size and function assessments during a non-rodent toxicology study using echocardiography proved great utility in this work. IDX14184 clinical development was eventually terminated due to suboptimal efficacy and regulatory concerns on potential heart and kidney injury in patients, as seen with a different guanosine nucleotide prodrug, BMS-986094.

scholarly journals The Scorpion Venom Peptide Smp76 Inhibits Viral Infection by Regulating Type-I Interferon Response

2018 ◽  
Vol 33 (6) ◽  
pp. 545-556 ◽  
Author(s):  
Zhenglin Ji ◽  
Fangfang Li ◽  
Zhiqiang Xia ◽  
Xingchen Guo ◽  
Minjun Gao ◽  
...  
Keyword(s):  
Viral Infection ◽  
Type I Interferon ◽  
Scorpion Venom ◽  
Interferon Response ◽  
Type I ◽  
Venom Peptide

scholarly journals Structure-Activity Relationships of the Human Immunodeficiency Virus Type 1 Maturation Inhibitor PF-46396

2016 ◽  
Vol 90 (18) ◽  
pp. 8181-8197 ◽  
Author(s):  
Christopher Murgatroyd ◽  
Lisa Pirrie ◽  
Fanny Tran ◽  
Terry K. Smith ◽  
Nicholas J. Westwood ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Betulinic Acid ◽  
Proteolytic Processing ◽  
Structure Activity Relationships ◽  
Modes Of Action ◽  
Structure Activity ◽  
Essential Properties ◽  
Maturation Inhibitor ◽  
The Relationship ◽  
Hiv 1

ABSTRACTHIV-1 maturation inhibitors are a novel class of antiretroviral compounds that consist of two structurally distinct chemical classes: betulinic acid derivatives and the pyridone-based compound PF-46396. It is currently believed that both classes act by similar modes of action to generate aberrant noninfectious particles via inhibition of CA-SP1 cleavage during Gag proteolytic processing. In this study, we utilized a series of novel analogues with decreasing similarity to PF-46396 to determine the chemical groups within PF-46396 that contribute to antiviral activity, Gag binding, and the relationship between these essential properties. A spectrum of antiviral activity (active, intermediate, and inactive) was observed across the analogue series with respect to CA-SP1 cleavage and HIV-1 (NL4-3) replication kinetics in Jurkat T cells. We demonstrate that selected inactive analogues are incorporated into wild-type (WT) immature particles and that one inactive analogue is capable of interfering with PF-46396 inhibition of CA-SP1 cleavage. Mutations that confer PF-46396 resistance can impose a defective phenotype on HIV-1 that can be rescued in a compound-dependent manner. Some inactive analogues retained the capacity to rescue PF-46396-dependent mutants (SP1-A3V, SP1-A3T, and CA-P157S), implying that they can also interact with mutant Gag. The structure-activity relationships observed in this study demonstrate that (i) thetert-butyl group is essential for antiviral activity but is not an absolute requirement for Gag binding, (ii) the trifluoromethyl group is optimal but not essential for antiviral activity, and (iii) the 2-aminoindan group is important for antiviral activity and Gag binding but is not essential, as its replacement is tolerated.IMPORTANCECombinations of antiretroviral drugs successfully treat HIV/AIDS patients; however, drug resistance problems make the development of new mechanistic drug classes an ongoing priority. HIV-1 maturation inhibitors are novel as they target the Gag protein, specifically by inhibiting CA-SP1 proteolytic cleavage. The lack of high-resolution structural information of the CA-SP1 target in Gag has hindered our understanding of the inhibitor-binding pocket and maturation inhibitor mode of action. Therefore, we utilized analogues of the maturation inhibitor PF-46396 as chemical tools to determine the chemical components of PF-46396 that contribute to antiviral activity and Gag binding and the relationship between these essential properties. This is the first study to report structure-activity relationships of the maturation inhibitor PF-46396. PF-46396 is chemically distinct from betulinic acid-derived maturation inhibitors; therefore, our data provide a foundation of knowledge that will aid our understanding of how structurally distinct maturation inhibitors act by similar modes of action.

scholarly journals The Extrapulmonary Manifestations of SARS-CoV-2

2021 ◽  
Vol 1 (1) ◽  
pp. 80-92
Author(s):  
Mohsin Majeed ◽  
Tayyaba Noor
Keyword(s):  
Viral Infection ◽  
Mechanism Of Action ◽  
Cell Membranes ◽  
Clinical Manifestations ◽  
The Body ◽  
Special Focus ◽  
Angiotensin Converting Enzyme 2 ◽  
Respiratory Cells ◽  
Multiple Drugs ◽  
Respiratory Outcomes

SARS-Coronavirus 2 (SARS-CoV-2) is the latest strain of coronavirus that causes the viral infection, Severe Acute Respiratory Syndrome (SARS). The initial studies on the Coronavirus Disease 2019 (COVID-19) focused on respiratory outcomes of this viral infection. More recent research on the mechanism of action of SARS-CoV-2 shows that the virus enters the cells through the Angiotensin-Converting Enzyme-2 (ACE-2) receptor. This receptor is present not just in the cell membranes of respiratory cells but also in the cell membranes of cells present in other organs of the body. This enables the virus to have severe outcomes in the body beyond the respiratory system. Providing a possible immunizing agent against coronavirus is a major challenge pertaining to the fact that ongoing pandemic has already taken millions of lives. This paper discusses the extrapulmonary effects of COVID-19, with an emphasis on clinical manifestations, mechanism of action, and special focus to management considerations in each of these cases. The essential therapeutics and treatments proposed for dealing with the COVID-19 infection have also been discussed. While the answer to whether these therapies work, successfully controlling the immunoinflammatory response is still unclear, ongoing trials of multiple drugs for this purpose are an excellent way to ultimately reach a product that works successfully.

scholarly journals Antiviral Effects of Plant Extracts Used in the Treatment of Important Animal Viral Diseases

2021 ◽  
Vol 11 (4) ◽  
pp. 521-533
Author(s):  
Gamil Sayed Gamil Zeedan ◽  
Abeer Mostafa Abdalhamed
Keyword(s):  
Antiviral Activity ◽  
Viral Infection ◽  
Plant Extracts ◽  
Rna Viruses ◽  
Biological Activities ◽  
Antiviral Drugs ◽  
Antiviral Compounds ◽  
Antiviral Activities

The goal of this review was to highlight some plant species that have significant antiviral activity against DNA and RNA viruses in vitro and in vivo although more research is needed to address safety issues, drug interactions, and the possibility of using them in combination with other natural products. Viral infection plays an important role in human and animal diseases. Although there have been advances in immunization and antiviral drugs, there is still a lack of protective vaccines and effective antiviral drugs in human and veterinary medicine. The lack of effective antivirals necessitates the search for new effective antiviral compounds. Plants are naturally gifted at synthesizing antiviral compounds. They are rich sources of phytochemicals with different biological activities, including antiviral activities as a result of advanced analytical chemistry, standard virus assays, and development of standardization and extraction methods. Plant extracts have a wide variety of active compounds, including flavonoids, terpenoids, lignans, sulphides, polyphenolics, coumarins, saponins, furyl compounds, alkaloids, polyines, thiophenes, proteins, and peptides. Moreover, certain volatile oils have indicated a high level of antiviral activity. Replication, assembly, and release, as well as targeting virus host-specific interactions capable of inhibiting several viruses, could help the development of broad-spectrum antivirals for the prevention and control of viral pathogens. The in vitro antiviral activities of Erythroxylum deciduum, Lacistema hasslerianum (chodat), Xylopia aromatica, Heteropteris aphrodisiaca, Acacia nilotica (gum arabic tree), Lippia graveolens (Guettarda angelica (Velvetseed), Prunus myrtifolia, and Symphyopappus plant extracts can inhibite viral replication, and interfer with the early stages of viral adsorption of DNA viruses. However, Boesenbergia rotunda plant extracts have inhibited RNA viruses. A potent anti-SARS-CoV-2 inhibitor with B. rotunda extract and panduratin A after viral infection drastically suppresses SARS-CoV-2 infectivity in Vero E6 cells.

Ovotransferrin expression and release by chicken cell lines infected with Marek’s disease virus

2007 ◽  
Vol 85 (1) ◽  
pp. 150-155 ◽  
Author(s):  
Francesco Giansanti ◽  
M. Federica Giardi ◽  
M. Teresa Massucci ◽  
Dario Botti ◽  
Giovanni Antonini
Keyword(s):  
Antiviral Activity ◽  
Viral Infection ◽  
Disease Virus ◽  
Chicken Embryo ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease ◽  
Lymphoblastoid Cells ◽  
Embryo Fibroblasts ◽  
Chicken Embryo Fibroblasts

Mammals posses both serum transferrin and lactoferrin, whose functions are taken over in birds by ovotransferrin, displaying both iron transport and antibacterial activities. Ovotransferrin also exerts antiviral activity towards Marek’s disease virus, an avian member of the herpes family of viruses. This virus infects lymphoid organs and induces the transcription of ovotransferrin in infected chicken embryo fibroblasts. However, it has not yet been established whether ovotransferrin gene transcription is linked to the release of the protein outside the cells or whether ovotransferrin expression and release also occurs in chicken lymphoblastoid cells in which the Marek’s disease viral genome is integrated. Our results indicate that both serum and egg-white isoforms of ovotransferrin are expressed and released in the supernatants of chicken embryo fibroblast and lymphoblastoid cells in the absence of infection. Viral infection of chicken embryo fibroblasts caused a slight increase of ovotransferrin release, whereas viral reinfection of lymphoblastoid cells caused a remarkable ovotransferrin release in a virus concentration-dependent manner. These findings suggest that ovotransferrin release in vivo may play a crucial role in protecting the whole organism from viral infection spreading, and support the hypothesis that the antiviral activity of ovotransferrin is an important part of the innate immune response in birds, resembling the antiviral activity of lactoferrin in mammals.

Protein Scaffold and Expression Level Determine Antiviral Activity of Membrane-Anchored Antiviral Peptides

2009 ◽  
Vol 20 (4) ◽  
pp. 325-336 ◽  
Author(s):  
Felix G. Hermann ◽  
Holger Martinius ◽  
Marc Egelhofer ◽  
Tsanan Giroglou ◽  
Torsten Tonn ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Expression Level ◽  
Protein Scaffold ◽  
Antiviral Peptides
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