Discovery of Bioactive Natural Products for the Treatment of Acute Respiratory Infections – An Integrated Approach

Planta Medica ◽  
2018 ◽  
Vol 84 (09/10) ◽  
pp. 684-695 ◽  
Author(s):  
Ulrike Grienke ◽  
Christina Mair ◽  
Johannes Kirchmair ◽  
Michaela Schmidtke ◽  
Judith Rollinger
Keyword(s):  
Antiviral Activity ◽  
Respiratory Infections ◽  
Antiviral Agents ◽  
Integrated Approach ◽  
Coxsackie Virus ◽  
Acute Respiratory Infections ◽  
Bioactive Natural Products ◽  
Antiviral Compounds ◽  
Antiviral Activities ◽  
Selection Of

AbstractIn this work, an integrated approach for the identification of new antiviral agents from natural sources for the treatment of acute respiratory infections is presented. The approach comprises (i) the selection of starting material based on traditional knowledge, (ii) phenotypic screening of extracts for antiviral activity, and (iii) the implementation of in silico predictions to identify antiviral compounds and derive the molecular mechanism underlying their biological activity. A variety of starting materials from plants and fungi was selected for the production of 162 extracts. These extracts were tested in cytopathic effect inhibition assays against influenza virus A/Hong Kong/68 (HK/68), rhinovirus A2 (RV-A2), and coxsackie virus B3 (CV-B3). All extracts were also evaluated regarding their cytotoxicity. At an IC50 threshold of 50 µg/mL, 20, 11, and 14% of all tested extracts showed antiviral activity against HK/68, CV-B3, and RV-A2, respectively. Among all active extracts (n = 47), 68% showed antiviral activity against one of the investigated viruses, whereas 31% inhibited at least two viruses. Herein, we present a comprehensive dataset of probed extracts along with their antiviral activities and cytotoxicity. Application examples presented in this work illustrate the phytochemical workflow for the identification of antiviral natural compounds. We also discuss the challenges, pitfalls, and advantages of the integrated approach.

scholarly journals The Combined Use of Alphavirus Replicons and Pseudoinfectious Particles for the Discovery of Antivirals Derived from Natural Products

2014 ◽  
Vol 20 (5) ◽  
pp. 673-680 ◽  
Author(s):  
Phillip C. Delekta ◽  
Avi Raveh ◽  
Martha J. Larsen ◽  
Pamela J. Schultz ◽  
Giselle Tamayo-Castillo ◽  
...  
Keyword(s):  
Life Cycle ◽  
Antiviral Activity ◽  
Viral Entry ◽  
Particle System ◽  
Antiviral Agents ◽  
Viral Life Cycle ◽  
Genome Replication ◽  
Bacterial Strains ◽  
Antiviral Compounds ◽  
Western Equine Encephalitis

Alphaviruses are a prominent class of reemergent pathogens due to their globally expanding ranges, potential for lethality, and possible use as bioweapons. The absence of effective treatments for alphaviruses highlights the need for innovative strategies to identify antiviral agents. Primary screens that use noninfectious self-replicating RNAs, termed replicons, have been used to identify potential antiviral compounds for alphaviruses. Only inhibitors of viral genome replication, however, will be identified using replicons, which excludes many other druggable steps in the viral life cycle. To address this limitation, we developed a western equine encephalitis virus pseudoinfectious particle system that reproduces several crucial viral life cycle steps in addition to genome replication. We used this system to screen a library containing ~26,000 extracts derived from marine microbes, and we identified multiple bacterial strains that produce compounds with potential antiviral activity. We subsequently used pseudoinfectious particle and replicon assays in parallel to counterscreen candidate extracts, and followed antiviral activity during biochemical fractionation and purification to differentiate between inhibitors of viral entry and genome replication. This novel process led to the isolation of a known alphavirus entry inhibitor, bafilomycin, thereby validating the approach for the screening and identification of potential antiviral compounds.

scholarly journals A New Range of Chitosan Based Nano-antiviral Agents

2021 ◽  
Vol 13 (1-2) ◽  
Author(s):  
Julio Garay-Jimenez
Keyword(s):  
Antiviral Activity ◽  
Antiviral Agents ◽  
Coxsackie Virus ◽  
Autoimmune Myocarditis ◽  
Capture Assay ◽  
Antigen Capture ◽  
Immunodeficiency Virus ◽  
P24 Antigen ◽  
Syncytial Virus ◽  
Hiv 1

ABSTRACT The current study involves the synthesis of fourteen analogs of oligochitosan and their screening for antiviral potential against human immunodeficiency virus (HIV), respiratory syncytial virus (RSV) and Coxsackie virus. The synthesized oligochitosan analogs were characterized by nuclear magnetic resonance (NMR) and FTIR techniques. HIV-1 p24 ELISA was performed using HIV-1 p24 antigen capture assay in order to estimate the viral infectivity loss. It was observed that sulfated oligochitosan was devoid of antiviral activity as compared to oligochitosan UN102 analog. The rest of UN102 analogs which include N-thiol (UN105), N-glutaryl (UN106), N-Azido (UN111) and N-phthaloyl (UN114) and N-citric analog (UN117) exhibited antiviral activity against HIV. The UN102 also decreased viral infection caused by RSV. In addition, UN102 was found to bind Coxsackie virus, which causes autoimmune myocarditis. The findings were of great interest to proceed for the development of novel antiviral agents.

Antiviral Medicinal Plants of Veterinary Importance: A Literature Review

Planta Medica ◽  
2020 ◽  
Vol 86 (15) ◽  
pp. 1058-1072
Author(s):  
Karin Zitterl-Eglseer ◽  
Tatiana Marschik
Keyword(s):  
Antiviral Activity ◽  
Plant Species ◽  
Influenza Viruses ◽  
Economic Losses ◽  
Virus Species ◽  
Animal Virus ◽  
Antiviral Compounds ◽  
Antiviral Activities ◽  
Veterinary Importance ◽  
Extract Fraction

AbstractViruses have a high mutation rate, and, thus, there is a continual emergence of new antiviral-resistant strains. Therefore, it becomes imperative to explore and develop new antiviral compounds continually. The search for pharmacological substances of plant origin that are effective against animal viruses, which have a high mortality rate or cause large economic losses, has garnered interest in the last few decades. This systematic review compiles 130 plant species that exhibit antiviral activity on 37 different virus species causing serious diseases in animals. The kind of extract, fraction, or compound exhibiting the antiviral activity and the design of the trial were particularly considered for review. The literature revealed details regarding plant species exhibiting antiviral activities against pathogenic animal virus species of the following families–Herpesviridae, Orthomyxoviridae, Paramyxoviridae, Parvoviridae, Poxviridae, Nimaviridae, Coronaviridae, Reoviridae, and Rhabdoviridae–that cause infections, among others, in poultry, cattle, pigs, horses, shrimps, and fish. Overall, 30 plant species exhibited activity against various influenza viruses, most of them causing avian influenza. Furthermore, 30 plant species were noted to be active against Newcastle disease virus. In addition, regarding the pathogens most frequently investigated, this review provides a compilation of 20 plant species active against bovine herpesvirus, 16 against fowlpox virus, 12 against white spot syndrome virus in marine shrimps, and 10 against suide herpesvirus. Nevertheless, some plant extracts, particularly their compounds, are promising candidates for the development of new antiviral remedies, which are urgently required.

scholarly journals Viral Etiology of Acute Respiratory Infections in Pediatric Patients in Lebanon

2019 ◽  
Vol 11 (1) ◽  
pp. e2019059
Author(s):  
Khaldoun Masoud ◽  
Ghassan Matar ◽  
Ghassan Dbaibo ◽  
Geoarge F Araj ◽  
Hasan Zaraket ◽  
...  
Keyword(s):  
High Frequency ◽  
Pediatric Patients ◽  
Respiratory Infections ◽  
Respiratory Viruses ◽  
Coxsackie Virus ◽  
Acute Respiratory Infections ◽  
Viral Etiology ◽  
Pcr Assay ◽  
Viral Pathogens ◽  
Parainfluenza Viruses

 Background: Acute respiratory infections (ARI) are the leading cause of death worldwide especially among children. The majority of these infections in children are of viral etiology. In this study, we evaluated the incidence of viral ARI among children in Lebanon. Methods: Children presenting with symptoms of ARI were prospectively recruited between September 2009 to February 2012. Nasopharyngeal aspirates were obtained from patients and screened for 11 respiratory viruses using a multiplex Luminex-based PCR assay. Results: Two hundred twenty-one patients were recruited with a median age of 1 year (IQR: 0 - 5). Out of 221 patients, 116 (52.5%) were positive for at least one virus, the majority (103/116; 88.8%) of which were in children under 6-year of age. Overall 188 viruses were detected. Rhinovirus (RhV) was the most common virus detected in 81 (69.8%) patients followed by coxsackie virus and echovirus (CVEV) which were detected as one target in the panel in 45 (38.8%), and parainfluenza viruses (PIV types: 1, 2, 3, 4) in 24 (20.7%) patients. Coinfection with more than one virus was detected in 49 (42.9%) patients. RhV and CVEV were the most common viruses associated with co-infections and higher risk of rhinorrhea. Conclusion: Viral pathogens account for at least half of the ARIs in Lebanon, with a high frequency of co-infections being detected.

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.

scholarly journals Antiviral activities of aerial subsets of Artemisia species against Herpes Simplex virus type 1 (HSV1) in vitro

2011 ◽  
Vol 5 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Mehrangiz Khajeh Karamoddini ◽  
Seyed Ahmad Emami ◽  
Masoud Sabouri Ghannad ◽  
Esmaeel Alizadeh Sani ◽  
Amirhossein Sahebkar
Keyword(s):  
Herpes Simplex ◽  
Antiviral Activity ◽  
Antiviral Agents ◽  
Positive Control ◽  
Type I ◽  
Viral Agent ◽  
Dye Absorption ◽  
Antiviral Activities ◽  
Simplex Virus

Abstract Background: Drug resistance to current anti-herpetic drugs has been increasingly reported. Therefore, there is a need for finding new antiviral agents, in particular from natural sources. Objective: In the present study, antiviral activity of subset extracts obtained from aerial parts of Artemisia including A. incana, A. chamaemelifolia, A. campesteris, A. fragrans, A. annua, A. vulgaris, and A. persica were investigated against Herpes Simplex type I (HSV1). Methods: Different concentrations of extracts (400, 200, 100, 50, 25, 12.5, 6.25, and 3.125 μg/mL) were obtained from subset of each plant separately, and used against KOS strain of HSV1 in HeLa cells. After 24 hours incubation, tetrazolium dye (MTT), was added. The dye absorption by viable cells was measured and compared to the positive control (extract-untreated cells) and acyclovir (as anti-viral agent). Results: The extracts obtained from A. annua had the highest antiviral activity while those of A. chamaemelifolia showed the lowest activity. Conclusion: Subset extracts of A. annua may be an appropriate candidate for further development of anti HSV1 infection.

scholarly journals Structure-dependent antiviral activity of catechol derivatives in pyroligneous acid against the encephalomycarditis virus

RSC Advances ◽  
2018 ◽  
Vol 8 (63) ◽  
pp. 35888-35896 ◽  
Author(s):  
Ruibo Li ◽  
Ryo Narita ◽  
Ryota Ouda ◽  
Chihiro Kimura ◽  
Hiroshi Nishimura ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Antiviral Compounds ◽  
Pyroligneous Acid ◽  
New Strategy ◽  
Antiviral Activities

The structure-related antiviral activities of catechol and derivatives were investigated. A new strategy for producing antiviral compounds was proposed.

scholarly journals Rapid Prescreening for Antiviral Agents against HIV-1 Based on Their Inhibitory Activity in Site-Directed Immunoassays. II. Porphyrins Reacting with the V3 Loop of gp120

1992 ◽  
Vol 3 (1) ◽  
pp. 55-63 ◽  
Author(s):  
A. R. Neurath ◽  
N. Strick ◽  
P. Haberfield ◽  
S. Jiang
Keyword(s):  
Antiviral Activity ◽  
Inhibitory Activity ◽  
Antiviral Agents ◽  
V3 Loop ◽  
Antiviral Compounds ◽  
Porphyrin Derivatives ◽  
Immunodeficiency Virus ◽  
Glycoprotein Gp120 ◽  
The Relationship ◽  
Hiv 1

Recent observations that haernin inhibited the replication of the human immunodeficiency virus (HIV-1) and the reaction between the HIV-1 envelope glycoprotein gp120 and antibodies specific for the V3 hypervariable loop of this glycoprotein were an enticement to determine whether or not additional porphyrins had similar activities. Several porphyrin derivatives, particularly meso-tetra (4-carboxyphenyl) porphine, were more potent inhibitors of HIV-1 replication than haernin. They blocked the binding of homologous antibodies to synthetic peptides corresponding to V3 hypervariable loops of 21 distinct HIV-1 isolates, and inhibited the replication in lymphocytic (MT-2) and promonocyte (U937) cell lines of several HIV-1 isolates, tested (IIIB, RF, SF-2, and MN). Compounds with inhibitory activity had a tetrapyrrole ring and, carboxyl or sulphonate groups. However, antiviral activity depended on minor structural difference's between distinct derivatives endowed with these two features. Metalloporphyrins had a drastically reduced antiviral activity in comparison with the corresponding porphyrins. An understanding of the relationship between the structure of porphyrins and their antiviral effects, perceptible from the results presented, is expected to lead to the design of additional derivatives with more potent antiviral activity and to unravelling of molecular details involved in the association between the V3 loop of gp120 and antiviral compounds targeted to this loop.

scholarly journals Inhibition of SARS-CoV-2 Virus Entry by the Crude Polysaccharides of Seaweeds and Abalone Viscera In Vitro

Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 219
Author(s):  
Sung-Kun Yim ◽  
Kian Kim ◽  
Inhee Kim ◽  
SangHo Chun ◽  
TaeHwan Oh ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Virus Entry ◽  
Antiviral Agents ◽  
Laminaria Japonica ◽  
Sulfated Polysaccharides ◽  
Total Carbohydrate ◽  
Porphyra Tenera ◽  
Antiviral Activities ◽  
Crude Polysaccharide

Much attention is being devoted to the potential of marine sulfated polysaccharides as antiviral agents in preventing COVID-19. In this study, sulfated fucoidan and crude polysaccharides, extracted from six seaweed species (Undaria pinnatifida sporophyll, Laminaria japonica, Hizikia fusiforme, Sargassum horneri, Codium fragile, Porphyra tenera) and Haliotis discus hannai (abalone viscera), were screened for their inhibitory activity against SARS-CoV-2 virus entry. Most of them showed significant antiviral activities at an IC50 of 12~289 μg/mL against SARS-CoV-2 pseudovirus in HEK293/ACE2, except for P. tenera (IC50 > 1000 μg/mL). The crude polysaccharide of S. horneri showed the strongest antiviral activity, with an IC50 of 12 μg/mL, to prevent COVID-19 entry, and abalone viscera and H. fusiforme could also inhibit SARS-CoV-2 infection with an IC50 of 33 μg/mL and 47 μg/mL, respectively. The common properties of these crude polysaccharides, which have strong antiviral activity, are high molecular weight (>800 kDa), high total carbohydrate (62.7~99.1%), high fucose content (37.3~66.2%), and highly branched polysaccharides. These results indicated that the crude polysaccharides from seaweeds and abalone viscera can effectively inhibit SARS-CoV-2 entry.

scholarly journals Investigation of monotherapy and combined anticoronaviral therapies against feline coronavirus serotype II in vitro

2021 ◽  
pp. 1098612X2110486
Author(s):  
Sarah E Cook ◽  
Helena Vogel ◽  
Diego Castillo ◽  
Mark Olsen ◽  
Niels Pedersen ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Antiviral Agents ◽  
Clinical Signs ◽  
Treatment Strategies ◽  
Antiviral Effect ◽  
Ocular Involvement ◽  
Virus Infections ◽  
Viral Inhibition ◽  
Antiviral Compounds

Objectives Feline infectious peritonitis (FIP), caused by genetic mutants of feline enteric coronavirus known as FIPV, is a highly fatal disease of cats with no currently available vaccine or US Food and Drug Administration-approved cure. Dissemination of FIPV in affected cats results in a range of clinical signs, including cavitary effusions, anorexia, fever and lesions of pyogranulomatous vasculitis and perivasculitis, with or without central nervous system or ocular involvement. The objectives of this study were to screen an array of antiviral compounds for anti-FIPV (serotype II) activity, determine cytotoxicity safety profiles of identified compounds with anti-FIPV activity and strategically combine identified monotherapies to assess compound synergy against FIPV in vitro. Based upon clinically successful combination treatment strategies for human patients with HIV and hepatitis C virus infections, we hypothesized that a combined anticoronaviral therapy approach featuring concurrent multiple mechanisms of drug action would result in an additive or synergistic antiviral effect. Methods This study screened 90 putative antiviral compounds for efficacy and cytotoxicity using a multimodal in vitro strategy, including plaque bioassays, real-time RT-PCR viral inhibition and cytotoxicity assays. Results Through this process, we identified 26 compounds with effective antiviral activity against FIPV, representing a variety of drug classes and mechanisms of antiviral action. The most effective compounds include GC376, GS-441524, EIDD2081 and EIDD2931. We documented antiviral efficacy for combinations of antiviral agents, with a few examined drug combinations demonstrating evidence of limited synergistic antiviral activity. Conclusions and relevance Although evidence of compound synergy was identified for several combinations of antiviral agents, monotherapies were ultimately determined to be the most effective in the inhibition of viral transcription.

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