scholarly journals The Broad-Spectrum Antiviral Potential of the Amphibian Peptide AR-23

2022 ◽  
Vol 23 (2) ◽  
pp. 883
Author(s):  
Annalisa Chianese ◽  
Carla Zannella ◽  
Alessandra Monti ◽  
Anna De Filippis ◽  
Nunzianna Doti ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Broad Spectrum ◽  
Viral Infections ◽  
Antiviral Agents ◽  
World Population ◽  
Therapeutic Effects ◽  
Amphibian Skin ◽  
Antibacterial And Antifungal Activities ◽  
Dna And Rna ◽  
Antibacterial And Antifungal

Viral infections represent a serious threat to the world population and are becoming more frequent. The search and identification of broad-spectrum antiviral molecules is necessary to ensure new therapeutic options, since there is a limited availability of effective antiviral drugs able to eradicate viral infections, and consequently due to the increase of strains that are resistant to the most used drugs. Recently, several studies on antimicrobial peptides identified them as promising antiviral agents. In detail, amphibian skin secretions serve as a rich source of natural antimicrobial peptides. Their antibacterial and antifungal activities have been widely reported, but their exploitation as potential antiviral agents have yet to be fully investigated. In the present study, the antiviral activity of the peptide derived from the secretion of Rana tagoi, named AR-23, was evaluated against both DNA and RNA viruses, with or without envelope. Different assays were performed to identify in which step of the infectious cycle the peptide could act. AR-23 exhibited a greater inhibitory activity in the early stages of infection against both DNA (HSV-1) and RNA (MeV, HPIV-2, HCoV-229E, and SARS-CoV-2) enveloped viruses and, on the contrary, it was inactive against naked viruses (PV-1). Altogether, the results indicated AR-23 as a peptide with potential therapeutic effects against a wide variety of human viruses.

scholarly journals A silkworm–baculovirus model for assessing the therapeutic effects of antiviral compounds: characterization and application to the isolation of antivirals from traditional medicines

2008 ◽  
Vol 89 (1) ◽  
pp. 188-194 ◽  
Author(s):  
Yutaka Orihara ◽  
Hiroshi Hamamoto ◽  
Hiroshi Kasuga ◽  
Toru Shimada ◽  
Yasushi Kawaguchi ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Vero Cells ◽  
Infection Model ◽  
Nuclear Magnetic Resonance Analysis ◽  
Therapeutic Effects ◽  
Traditional Medicines ◽  
Baculovirus Infection ◽  
Simplex Virus

Ganciclovir, foscarnet, vidarabine and ribavirin, which are used to treat viral infections in humans, inhibited the proliferation of a baculovirus (Bombyx mori nucleopolyhedrovirus) in BmN4 cells, a cultured silkworm cell line. These antiviral agents inhibited the proliferation of baculovirus in silkworm body fluid and had therapeutic effects. Using the silkworm infection model, the antiviral activity of Kampo medicines was screened and it was found that cinnamon bark, a component of the traditional Japanese medicine Mao-to, had a therapeutic effect. Based on the therapeutic activity, the antiviral substance was purified. Nuclear magnetic resonance analysis of the purified fraction revealed that the antiviral activity was due to cinnzeylanine, which has previously been isolated from Cinnamomum zeylanicum. Cinnzeylanine inhibits the proliferation of herpes simplex virus type 1 in Vero cells. These results suggest that the silkworm–baculovirus infection model is useful for screening antiviral agents that are effective for treating humans infected with DNA viruses.

scholarly journals NAD+-consuming enzymes in immune defense against viral infection

2021 ◽  
Vol 478 (23) ◽  
pp. 4071-4092
Author(s):  
Jialin Shang ◽  
Michael R. Smith ◽  
Ananya Anmangandla ◽  
Hening Lin
Keyword(s):  
Immune Responses ◽  
Broad Spectrum ◽  
Defense Mechanisms ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Scientific Progress ◽  
Immune Defense ◽  
Past Century ◽  
Antiviral Immune Response ◽  
Antiviral Function

The COVID-19 pandemic reminds us that in spite of the scientific progress in the past century, there is a lack of general antiviral strategies. In analogy to broad-spectrum antibiotics as antibacterial agents, developing broad spectrum antiviral agents would buy us time for the development of vaccines and treatments for future viral infections. In addition to targeting viral factors, a possible strategy is to understand host immune defense mechanisms and develop methods to boost the antiviral immune response. Here we summarize the role of NAD+-consuming enzymes in the immune defense against viral infections, with the hope that a better understanding of this process could help to develop better antiviral therapeutics targeting these enzymes. These NAD+-consuming enzymes include PARPs, sirtuins, CD38, and SARM1. Among these, the antiviral function of PARPs is particularly important and will be a focus of this review. Interestingly, NAD+ biosynthetic enzymes are also implicated in immune responses. In addition, many viruses, including SARS-CoV-2 contain a macrodomain-containing protein (NSP3 in SARS-CoV-2), which serves to counteract the antiviral function of host PARPs. Therefore, NAD+ and NAD+-consuming enzymes play crucial roles in immune responses against viral infections and detailed mechanistic understandings in the future will likely facilitate the development of general antiviral strategies.

scholarly journals Penaeidins, antimicrobial peptides with chitin-binding activity, are produced and stored in shrimp granulocytes and released after microbial challenge

2000 ◽  
Vol 113 (3) ◽  
pp. 461-469 ◽  
Author(s):  
D. Destoumieux ◽  
M. Munoz ◽  
C. Cosseau ◽  
J. Rodriguez ◽  
P. Bulet ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Binding Activity ◽  
Penaeus Vannamei ◽  
Mrna Levels ◽  
Cytoplasmic Granules ◽  
Antibacterial And Antifungal Activities ◽  
New Family ◽  
Antibacterial And Antifungal ◽  
And Storage ◽  
Microbial Challenge

Penaeidins are members of a new family of antimicrobial peptides isolated from a crustacean, which present both Gram-positive antibacterial and antifungal activities. We have studied the localization of synthesis and storage of penaeidins in the shrimp Penaeus vannamei. The distribution of penaeidin transcripts and peptides in various tissues reveals that penaeidins are constitutively synthesized and stored in the shrimp haemocytes. It was shown by immunocytochemistry, at both optical and ultrastructural levels, that the peptides are localized in granulocyte cytoplasmic granules. The expression and localization of penaeidins were further analysed in shrimp subjected to microbial challenge. We found that (1) penaeidin mRNA levels decrease in circulating haemocytes in the first 3 hours following stimulation and (2) an increase in plasma penaeidin concentration occurs after microbial challenge, together with (3) a penaeidin immunoreactivity in cuticular tissue, which can be related to the chitin-binding activity we demonstrate here for penaeidins.

Synthesis, antibacterial, and antifungal activities of new pyrimidinone derivatives

2015 ◽  
Vol 21 (4) ◽  
pp. 191-194 ◽  
Author(s):  
Oussama Cherif ◽  
Fatma Masmoudi ◽  
Fatma Allouche ◽  
Fakher Chabchoub ◽  
Mohamed Trigui
Keyword(s):  
Antimicrobial Activity ◽  
Broad Spectrum ◽  
Pathogenic Fungi ◽  
Gram Negative Bacteria ◽  
Efficient Synthesis ◽  
Gram Negative ◽  
Antifungal Activities ◽  
Antibacterial And Antifungal Activities ◽  
Bacteria And Fungi ◽  
Antibacterial And Antifungal

AbstractAn efficient synthesis of new pyrrolopyrimidinones 3a-d and isoxazolopyrimidinones 4a-c from the respective aminocyanopyrroles 1a-d and aminocyanoisoxazoles 2a-c is presented. The synthesized compounds were screened for antimicrobial activity against a panel of bacteria and fungi. Compound 4c exhibits remarkable activity against a broad spectrum of Gram-positive and Gram-negative bacteria and pathogenic fungi.

scholarly journals Antiviral Compounds from Myxobacteria

2018 ◽  
Vol 6 (3) ◽  
pp. 73 ◽  
Author(s):  
Lucky Mulwa ◽  
Marc Stadler
Keyword(s):  
Broad Spectrum ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Public Health Issue ◽  
Target Cells ◽  
Global Public Health ◽  
Drug Candidates ◽  
Antiviral Compounds ◽  
Spectrum Activity

Viral infections including human immunodeficiency virus (HIV), cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) pose an ongoing threat to human health due to the lack of effective therapeutic agents. The re-emergence of old viral diseases such as the recent Ebola outbreaks in West Africa represents a global public health issue. Drug resistance and toxicity to target cells are the major challenges for the current antiviral agents. Therefore, there is a need for identifying agents with novel modes of action and improved efficacy. Viral-based illnesses are further aggravated by co-infections, such as an HIV patient co-infected with HBV or HCV. The drugs used to treat or manage HIV tend to increase the pathogenesis of HBV and HCV. Hence, novel antiviral drug candidates should ideally have broad-spectrum activity and no negative drug-drug interactions. Myxobacteria are in the focus of this review since they produce numerous structurally and functionally unique bioactive compounds, which have only recently been screened for antiviral effects. This research has already led to some interesting findings, including the discovery of several candidate compounds with broad-spectrum antiviral activity. The present review looks at myxobacteria-derived antiviral secondary metabolites.

scholarly journals Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents

2016 ◽  
Vol 113 (19) ◽  
pp. 5388-5393 ◽  
Author(s):  
Annalaura Brai ◽  
Roberta Fazi ◽  
Cristina Tintori ◽  
Claudio Zamperini ◽  
Francesca Bugli ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Host Factor ◽  
Human Pathogens ◽  
Genetic Barrier ◽  
Dna And Rna ◽  
Development Of Resistance ◽  
Emerging Viral Diseases ◽  
Hiv 1

Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEAD-box polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus. Herein, we showed for the first time, to our knowledge, that the inhibition of DDX3 by a small molecule could be successfully exploited for the development of a broad spectrum antiviral agent. In addition to the multiple antiviral activities, hit compound 16d retained full activity against drug-resistant HIV-1 strains in the absence of cellular toxicity. Pharmacokinetics and toxicity studies in rats confirmed a good safety profile and bioavailability of 16d. Thus, DDX3 is here validated as a valuable therapeutic target.

scholarly journals Development of Broad-Spectrum Antiviral Agents—Inspiration from Immunomodulatory Natural Products

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1257
Author(s):  
Mengxun Zhang ◽  
Jiaqing Zhong ◽  
Yongai Xiong ◽  
Xun Song ◽  
Chenyang Li ◽  
...  
Keyword(s):  
Natural Products ◽  
Broad Spectrum ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Antiviral Drugs ◽  
Life Cycles ◽  
The Body ◽  
Host Cells ◽  
Immunomodulatory Effects ◽  
Antiviral Effects

Developing broad-spectrum antiviral drugs remains an important issue as viral infections continue to threaten public health. Host-directed therapy is a method that focuses on potential targets in host cells or the body, instead of viral proteins. Its antiviral effects are achieved by disturbing the life cycles of pathogens or modulating immunity. In this review, we focus on the development of broad-spectrum antiviral drugs that enhance the immune response. Some natural products present antiviral effects mediated by enhancing immunity, and their structures and mechanisms are summarized here. Natural products with immunomodulatory effects are also discussed, although their antiviral effects remain unknown. Given the power of immunity and the feasibility of host-directed therapy, we argue that both of these categories of natural products provide clues that may be beneficial for the discovery of broad-spectrum antiviral drugs.

scholarly journals Identification and Characterization of Antimicrobial Peptides From Butterflies: An Integrated Bioinformatics and Experimental Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Wang ◽  
Ziyue Zhou ◽  
Simin Li ◽  
Wei Zhu ◽  
Xianda Hu
Keyword(s):  
Antimicrobial Peptides ◽  
Therapeutic Potential ◽  
Biological Effects ◽  
Future Research ◽  
Nucleic Acid Binding ◽  
Antibacterial And Antifungal Activities ◽  
Antibacterial And Antifungal ◽  
Biophysical Changes

Butterflies represent one of the largest animal groups on Earth, yet antimicrobial peptides (AMPs) of this group are less studied in comparison with their moth counterparts. This study employed an integrated bioinformatics approach to survey natural AMPs from publicly available genomic datasets. Numerous AMPs, including cecropins, defensins, and moricins, were identified and subsequently used as templates for the design of a series of synthetic AMPs that mimicked the naturally occurring sequences. Despite differing biological effects among the various sequences, the synthetic AMPs exhibited potent antibacterial and antifungal activities in vitro and in vivo, without inducing hemolysis, which implied their therapeutic potential in infectious diseases. Electron and confocal fluorescence microscopies revealed that the AMPs induced distinct morphological and biophysical changes on microbial cell membranes and nuclei, suggesting that the antimicrobial effects were related to a mechanism of membrane penetration and nucleic acid binding by the peptides. In conclusion, this study not only offers insights into butterfly AMPs but also provides a practical strategy for high-throughput natural AMP discoveries that will have implications for future research in this area.

scholarly journals Ionophore antibiotic X-206 is a potent and selective inhibitor of SARS-CoV-2 infection in vitro

2020 ◽  
Author(s):  
Esben B. Svenningsen ◽  
Jacob Thyrsted ◽  
Julia Blay-Cadanet ◽  
Han Liu ◽  
Shaoquan Lin ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Antiviral Agents ◽  
Host Cells ◽  
World Population ◽  
Antiviral Therapies ◽  
The Family ◽  
Pathogenic Viruses ◽  
Antiviral Mechanism ◽  
Treatment Of Infection

AbstractPandemic spread of emerging human pathogenic viruses such as the current SARS-CoV-2, poses both an immediate and future challenge to human health and society. Currently, effective treatment of infection with SARS-CoV-2 is limited and broad spectrum antiviral therapies to meet other emerging pandemics are absent leaving the World population largely unprotected. Here, we have identified distinct members of the family of polyether ionophore antibiotics with potent ability to inhibit SARS-CoV-2 replication and cytopathogenicity in cells. Several compounds from this class displayed more than 100-fold selectivity between viral-induced cytopathogenicity and inhibition of cell viability, however the compound X-206 displayed >500-fold selectivity and was furthermore able to inhibit viral replication even at sub-nM levels. The antiviral mechanism of the polyether ionophores is currently not understood in detail. We demonstrate, through unbiased bioactivity profiling, that their effects on the host cells differ from those of cationic amphiphiles such as hydroxychloroquine. Collectively, our data suggest that polyether ionophore antibiotics should be subject to further investigations as potential broad-spectrum antiviral agents.

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