scholarly journals Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation

2020 ◽  
Vol 9 (4) ◽  
pp. 959
Author(s):  
Isaac Hurtado-Guerrero ◽  
Bruno Hernáez ◽  
María J. Pinto-Medel ◽  
Esther Calonge ◽  
José L. Rodriguez-Bada ◽  
...  

Soluble receptors of cytokines are able to modify cytokine activities and therefore the immune system, and some have intrinsic biological activities without mediation from their cytokines. The soluble interferon beta (IFN-ß) receptor is generated through alternative splicing of IFNAR2 and has both agonist and antagonist properties for IFN-ß, but its role is unknown. We previously demonstrated that a recombinant human soluble IFN-ß receptor showed intrinsic therapeutic efficacy in a mouse model of multiple sclerosis. Here we evaluate the potential biological activities of recombinant sIFNAR2 without the mediation of IFN-ß in human cells. Recombinant sIFNAR2 down-regulated the production of IL-17 and IFN-ɣ and reduced the cell proliferation rate. Moreover, it showed a strong antiviral activity, fully protecting the cell monolayer after being infected by the virus. Specific inhibitors completely abrogated the antiviral activity of IFN-ß, but not that of the recombinant sIFNAR2, and there was no activation of the JAK-STAT signaling pathway. Consequently, r-sIFNAR2 exerts immunomodulatory, antiproliferative and antiviral activities without IFN-ß mediation, and could be a promising treatment against viral infections and immune-mediated diseases.

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 87 ◽  
Author(s):  
Alberto Falco ◽  
Regla Medina-Gali ◽  
José Poveda ◽  
Melissa Bello-Perez ◽  
Beatriz Novoa ◽  
...  

Global health is under attack by increasingly-frequent pandemics of viral origin. Antimicrobial peptides are a valuable tool to combat pathogenic microorganisms. Previous studies from our group have shown that the membrane-lytic region of turbot (Scophthalmus maximus) NK-lysine short peptide (Nkl71–100) exerts an anti-protozoal activity, probably due to membrane rupture. In addition, NK-lysine protein is highly expressed in zebrafish in response to viral infections. In this work several biophysical methods, such as vesicle aggregation, leakage and fluorescence anisotropy, are employed to investigate the interaction of Nkl71–100 with different glycerophospholipid vesicles. At acidic pH, Nkl71–100 preferably interacts with phosphatidylserine (PS), disrupts PS membranes, and allows the content leakage from vesicles. Furthermore, Nkl71–100 exerts strong antiviral activity against spring viremia of carp virus (SVCV) by inhibiting not only the binding of viral particles to host cells, but also the fusion of virus and cell membranes, which requires a low pH context. Such antiviral activity seems to be related to the important role that PS plays in these steps of the replication cycle of SVCV, a feature that is shared by other families of virus-comprising members with health and veterinary relevance. Consequently, Nkl71–100 is shown as a promising broad-spectrum antiviral candidate.


Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 224 ◽  
Author(s):  
Natalya V. Krylova ◽  
Svetlana P. Ermakova ◽  
Vyacheslav F. Lavrov ◽  
Irina A. Leneva ◽  
Galina G. Kompanets ◽  
...  

The enzymatic depolymerization of fucoidans from brown algae allowed the production of their standardized derivatives with different biological activities. This work aimed to compare the antiviral activities of native (FeF) and modified with enzyme (FeHMP) fucoidans from F. evanescens. The cytotoxicity and antiviral activities of the FeF and FeHMP against herpes viruses (HSV-1, HSV-2), enterovirus (ECHO-1), and human immunodeficiency virus (HIV-1) in Vero and human MT-4 cell lines were examined by methylthiazolyltetrazolium bromide (MTT) and cytopathic effect (CPE) reduction assays, respectively. The efficacy of fucoidans in vivo was evaluated in the outbred mice model of vaginitis caused by HSV-2. We have shown that both FeF and FeHMP significantly inhibited virus-induced CPE in vitro and were more effective against HSV. FeF exhibited antiviral activity against HSV-2 with a selective index (SI) > 40, and FeHMP with SI ˃ 20, when they were added before virus infection or at the early stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that after intraperitoneal administration (10 mg/kg), both FeF and FeHMP protected mice from lethal intravaginal HSV-2 infection to approximately the same degree (44–56%). Thus, FeF and FeHMP have comparable potency against several DNA and RNA viruses, allowing us to consider the studied fucoidans as promising broad-spectrum antivirals.


2020 ◽  
Vol 12 ◽  
pp. 1759720X2094729
Author(s):  
Y. C. Tsai ◽  
T. F. Tsai

There have been several episodes of viral infection evolving into epidemics in recent decades, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the latest example. Its high infectivity and moderate mortality have resulted in an urgent need to find an effective treatment modality. Although the category of immunosuppressive drugs usually poses a risk of infection due to interference of the immune system, some of them have been found to exert antiviral properties and are already used in daily practice. Recently, hydroxychloroquine and baricitinib have been proposed as potential drugs for SARS-CoV-2. In fact, there are other immunosuppressants known with antiviral activities, including cyclosporine A, hydroxyurea, minocycline, mycophenolic acid, mycophenolate mofetil, leflunomide, tofacitinib, and thalidomide. The inherent antiviral activity could be a treatment choice for patients with coexisting rheumatological disorders and infections. Clinical evidence, their possible mode of actions and spectrum of antiviral activities are included in this review article. Lay summary Immunosuppressants often raise the concern of infection risks, especially for patients with underlying immune disorders. However, some disease-modifying antirheumatic drugs (DMARDs) with inherent antiviral activity would be a reasonable choice in the situation of concomitant viral infections and flare up of autoimmune diseases. This review covers DMARDs of treatment potential for SARS-CoV-2 in part I, and antiviral mechanisms plus trial evidence for viruses other than SARS-CoV-2 in part II.


2021 ◽  
Vol 11 (4) ◽  
pp. 521-533
Author(s):  
Gamil Sayed Gamil Zeedan ◽  
Abeer Mostafa Abdalhamed

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.


1997 ◽  
Vol 75 (10) ◽  
pp. 1656-1660 ◽  
Author(s):  
J. H. Kim ◽  
A. M. Huang ◽  
K. Bannister ◽  
T. J. Choi ◽  
G. H. N. Towers ◽  
...  

We report the results of the first screening of 89 seaweeds collected from British Columbia, Canada, and Korea for antiviral activity. Various concentrations of methanol extracts of dried algae were tested against 100 plaque-forming units of herpes simplex virus type 1 and Sindbis virus in Vero cell monolayers. Eleven extracts inhibited both viruses, and 22 extracts were active against only one of the viruses. Thus, in total 37% of the species were active, and only two of these extracts also showed cytotoxicity at the concentrations tested. The antiviral activities were proportionately more frequent in the Korean extracts (56% compared with 27% of Canadian extracts), but in general the more potent extracts were of Canadian origin. Analipus japonicus was the most potent anti-herpes species, and the Korean species of Codium fragile was the most potent against both viruses. This high yield of antiviral extracts illustrates the potential of seaweeds as a resource for bioactive compounds. Key words: seaweeds, algal extracts, antiviral activities.


2020 ◽  
Author(s):  
Sindhu KC ◽  
Manoj Pandit ◽  
Amit Kumar Shrivastava

Abstract Coronavirus is a non-segmented, positive-sense RNA genome belonging to the family coronaviridae in the order Nidovirales Corona viral infections have created serious threats in the last couple of decades and recently claiming the death of thousands of human beings. Natural products provide a valuable and powerful resource of chemical compounds alkaloids, tannins, caffeine, biopterin, actinophnine, etc. displaying antiviral properties. The data was reviewed from various databases or search engines: PubMed, Science Direct, MedLine, Google Scholar, and Biomed central for published articles. The data inclusion criteria was natural products and their isolated and different synthetic compounds. Data duplication and titles or contents that do not meet the inclusion criteria and Reports on antiviral activities of natural products or their derivatives against other than CoV strains were excluded. We encountered 49 plants and 19 compound chemically defined natural molecules reported in the literature, which have evaluated for potent antiviral activity against different coronavirus strains. The listed plants and their compounds in this review are highly potent with promising results against coronavirus. These can be further screened for invasive tests and used for making different formulations or may be polyherbal formulations considering its safety profile and toxicity.


2016 ◽  
Author(s):  
Liubov Biliavska ◽  
Yulia Pankivska ◽  
Olga Povnitsa ◽  
Svitlana Zagorodnya ◽  
Ganna Gudz ◽  
...  

1980 ◽  
Vol 45 (8) ◽  
pp. 2364-2370 ◽  
Author(s):  
Antonín Holý ◽  
Erik De Clercq

Reaction of 3',5'-di-O-benzoyl-6-methyl-2'-deoxyuridine (IIa) with elementary bromine or iodine afforded 5-halogeno derivatives IIc and IId which on methanolysis gave 5-bromo-6-methyl-2'-deoxyurine (Ic) and 5-iodo-6-methyl-2'-deoxyurine (Id), respectively. The CD spectra of Ic, Id and 6-methyl-2'-deoxyuridine (Ia) are compared and discussed with regard to determination of the nucleoside conformation. Unlike 5-bromo- and 5-iodo-2'-deoxyuridine, the 6-methyl derivatives Ic and Id exhibit neither antibacterial nor antiviral activity. Nor do they exert any antimetabolic effect on the de novo DNA synthesis in primary rabbit kidney cells.


Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 92 ◽  
Author(s):  
Alessia Catalano ◽  
Domenico Iacopetta ◽  
Michele Pellegrino ◽  
Stefano Aquaro ◽  
Carlo Franchini ◽  
...  

Antimicrobials have allowed medical advancements over several decades. However, the continuous emergence of antimicrobial resistance restricts efficacy in treating infectious diseases. In this context, the drug repositioning of already known biological active compounds to antimicrobials could represent a useful strategy. In 2002 and 2003, the SARS-CoV pandemic immobilized the Far East regions. However, the drug discovery attempts to study the virus have stopped after the crisis declined. Today’s COVID-19 pandemic could probably have been avoided if those efforts against SARS-CoV had continued. Recently, a new coronavirus variant was identified in the UK. Because of this, the search for safe and potent antimicrobials and antivirals is urgent. Apart from antiviral treatment for severe cases of COVID-19, many patients with mild disease without pneumonia or moderate disease with pneumonia have received different classes of antibiotics. Diarylureas are tyrosine kinase inhibitors well known in the art as anticancer agents, which might be useful tools for a reposition as antimicrobials. The first to come onto the market as anticancer was sorafenib, followed by some other active molecules. For this interesting class of organic compounds antimicrobial, antiviral, antithrombotic, antimalarial, and anti-inflammatory properties have been reported in the literature. These numerous properties make these compounds interesting for a new possible pandemic considering that, as well as for other viral infections also for CoVID-19, a multitarget therapeutic strategy could be favorable. This review is meant to be an overview on diarylureas, focusing on their biological activities, not dwelling on the already known antitumor activity. Quite a lot of papers present in the literature underline and highlight the importance of these molecules as versatile scaffolds for the development of new and promising antimicrobials and multitarget agents against new pandemic events.


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