scholarly journals Pathogenic Viruses Commonly Present in the Oral Cavity and Relevant Antiviral Compounds Derived from Natural Products

Medicines ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 120 ◽  
Author(s):  
Daisuke Asai ◽  
Hideki Nakashima

Many viruses, such as human herpesviruses, may be present in the human oral cavity, but most are usually asymptomatic. However, if individuals become immunocompromised by age, illness, or as a side effect of therapy, these dormant viruses can be activated and produce a variety of pathological changes in the oral mucosa. Unfortunately, available treatments for viral infectious diseases are limited, because (1) there are diseases for which no treatment is available; (2) drug-resistant strains of virus may appear; (3) incomplete eradication of virus may lead to recurrence. Rational design strategies are widely used to optimize the potency and selectivity of drug candidates, but discovery of leads for new antiviral agents, especially leads with novel structures, still relies mostly on large-scale screening programs, and many hits are found among natural products, such as extracts of marine sponges, sea algae, plants, and arthropods. Here, we review representative viruses found in the human oral cavity and their effects, together with relevant antiviral compounds derived from natural products. We also highlight some recent emerging pharmaceutical technologies with potential to deliver antivirals more effectively for disease prevention and therapy.

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 48s-48s
Author(s):  
L. Kennedy ◽  
S. Bejarano ◽  
E.P. Larochelle ◽  
G.J. Tsongalis

Background: Poverty, poor healthcare infrastructure and geographic location contribute to a total lack of cancer screening for most residents of rural Honduras. Three projects built upon each other to develop, with local leaders, multiorgan screening events that mitigated barriers to screening-based early detection of cancers. Targeted barriers included transportation, cost, community perception and convenience. Aim: To test a novel system of multiorgan screening for feasibility, acceptability and effectiveness. Methods: Leveraging well-known brigade-style medical outreach methods, two large-scale weekend programs for women and one for men over four years in the same rural location screened women for cancers of the cervix, breast, oral cavity, thyroid; and men for cancers of the testes, oral cavity, skin, prostate and colon; and connected participants with follow-up care at a Honduran cancer center. Screening methods ranged from simple throat palpation for thyroid lesions to molecular screening for high risk HPV. Generally, screening began with low-tech methods onsite to triage the participants and identify those at high-risk for cancer who should have more technical follow-up at an equipped clinic. Well-trained Honduran medical students provided screening capacity and community leaders were solely responsible for promoting the screening opportunities. Masking was not possible onsite, but data analysis in the U.S. was anonymized. Results: Participants were accrued to each program's capacity (n=400) in 2013 and 2016 and near capacity in 2017 with high levels of participants completing the screening programs, community engagement with the process, and compliance with referrals for clinical follow-up at a collaborating cancer center located three hours away. Participants identified at the screenings for clinical follow-up included for women: breast 2.7% (2013) and 4.2% (2016), thyroid 1.7% (2016), cervix/positive for high risk HPV 8.2% (2013) and 11.8% (2016); and for men all in 2017: skin 0%, testes 7%, colorectal 1%, oropharynx 1 participant, and prostate 6.7%. The dominant local narrative predicted men would not participate in screening, yet 326 participated and of that group, 239 self-identified as having possible colorectal symptoms based on seeing an advertising flyer with questions about symptoms of constipation, bloody stools, or unintended weight loss. That self-identified subset took the initiative to see the local nurse in advance, obtain a colorectal sample kit, collect three days of stool samples, and bring them to the screening event. Conclusion: With community engagement and attention to planning for organized and rapid throughput, large-scale multiorgan cancer screening may be feasible in low-income rural communities. Funding: The Jornada studies were funded by Norris Cotton Cancer Center at Dartmouth's Geisel School of Medicine and a special grant from Geisel's Munck-Pfefferkorn Fund.


2011 ◽  
Vol 26 (2) ◽  
pp. 31
Author(s):  
R. N. Águila-Ramírez ◽  
C. J. Hernández-Guerrero ◽  
B. González-Acosta

La búsqueda de productos naturales con actividad farmacológica a partir de esponjas marinas tiene un gran potencial debido a las interesantes actividades que algunos compuestos presentan en ensayos clínicos, principalmente en la búsqueda de compuestos anticancerígenos y antivirales. Sin embargo, también existen diversas problemáticas que pueden frenar el desarrollo de un nuevo compuesto. Por lo que en esta revisión se pretende dar un panorama general de las perspectivas y limitantes que se presentan en la búsqueda de nuevos compuestos a partir de esponjas en el medio natural, en el establecimiento de cultivos de esponjas, de primorfos y células madre como una alternativa o el aislamiento de bacterias asociadas a ellas que produzcan dichos metabolitos con la finalidad de realizar modificaciones genéticas que permitan una producción biotecnológica. Biotechnical potential of sponges in new pharmaceutics production: perspectives and limits The search for natural products with pharmacological activity of marine sponges has great potential due to the interesting activities that some compounds have in clinical trials, mainly in the search of anticancer and antiviral compounds. However, there are various problems that may limit the development of a new compound. In this review we intended to give an overview of the perspectives and limitations that occur in the search of new compounds from sponges of the natural environment, in the establishment of culture of sponges, primorph and steam cells as an alternative, or isolated bacteria from sponges which are the metabolites producers to development genetic modifications for a biotechnological production.


2009 ◽  
Vol 81 (6) ◽  
pp. 1113-1121 ◽  
Author(s):  
Dovi Kelman ◽  
Yoel Kashman ◽  
Russell T. Hill ◽  
Eugene Rosenberg ◽  
Yossi Loya

Marine sponges and corals are widely recognized as rich sources of novel bioactive natural products. These organisms are frequently colonized by bacteria. Some of these bacteria can be pathogenic or serve as beneficial symbionts. Therefore, these organisms need to regulate the bacteria they encounter and resist microbial pathogens. One method is by chemical defense. Antimicrobial assays performed with extracts of 23 Red Sea corals and sponges against bacteria isolated from their natural environment revealed considerable variability in antimicrobial activity. Soft corals exhibited appreciable activity; sponges showed variability, and stony corals had little or no activity. Among the soft corals, Xenia macrospiculata exhibited the highest activity. Bioassay-directed fractionation of the extract indicated that the activity was due to a range of compounds, one of which was isolated and identified as the diterpene desoxyhavannahine. Among the sponges, Amphimedon chloros exhibited strong activity. Bioassay-directed fractionation resulted in the isolation of the pyridinium alkaloid antibiotics, the halitoxins and amphitoxins. These compounds showed selective activity against specific bacteria, rather than being broad-spectrum. They were highly active against seawater bacteria, whereas bacteria associated with the sponge were resistant. This selective toxicity may be important in enabling certain bacteria to live in close association with their sponge host while it maintains a chemical defense against microbial pathogenesis. The halitoxin-resistant bacteria were identified by 16S rRNA gene analysis as Alphaproteobacteria, closely related to other Alphaproteobacteria isolated from various marine sponges. The study of microbial communities associated with sponges and corals has important implications for the production of symbiont-derived bioactive compounds and for the use of corals and sponges as source material for microbial diversity in screening programs for natural products.


2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Nuno Vale ◽  
Maria João Gouveia ◽  
Gabriel Rinaldi ◽  
Paul J. Brindley ◽  
Fátima Gärtner ◽  
...  

ABSTRACT Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. PZQ is the drug of choice for the treatment of schistosomiasis; it is effective against all major forms of schistosomiasis, although it is less active against juvenile than mature parasites. A pyrazino-isoquinoline derivative, PZQ is not considered to be toxic and generally causes few or transient, mild side effects. Increasingly, mass drug administration targeting populations in sub-Saharan Africa where schistosomiasis is endemic has led to the appearance of reduced efficacy of PZQ, which portends the selection of drug-resistant forms of these pathogens. The synthesis of improved derivatives of PZQ is attracting attention, e.g., in the (i) synthesis of drug analogues, (ii) rational design of pharmacophores, and (iii) discovery of new compounds from large-scale screening programs. This article reviews reports from the 1970s to the present on the metabolism and mechanism of action of PZQ and its derivatives against schistosomes.


Author(s):  
Carsten Thoms ◽  
Peter Schupp

AbstractThroughout human history natural products have provided the basis for medicinal treatment. About 60 years ago the advent of SCUBA diving techniques granted access to a thitherto untapped source of pharmacologically highly active natural products: the marine environment. In the oceans not plants but sessile animals, particularly sponges, have proven to be the most fruitful organisms in this context. Sponges have evolved a vast arsenal of chemical weapons to defend themselves against various threats from their environment. These molecules remarkably often show potent activities in pharmaceutical assays. Several sponge-derived compounds are already in clinical trials as agents against cancer, microbial infections, inflammation and other diseases. However, in many cases drug development is severely hampered by the limited supply of the respective compounds, as they are often present only in minute amounts in the sponge tissue. Big hope to circumvent this obstacle lies on the supposition that sponge-associated bacteria and not the sponges themselves are in many cases the true producers of the pharmaceutically relevant agents. Once these microorganisms are determined and cultivated outside the sponge tissue, they could be fermented for large-scale compound production. This in future could substantially increase the number of powerful sponge-derived drugs on the market.


2016 ◽  
Vol 23 (4) ◽  
pp. 360-382 ◽  
Author(s):  
Mousa Alghazwi ◽  
Yen Qi Kan ◽  
Wei Zhang ◽  
Wei Ping Gai ◽  
Xiao-Xin Yan

2012 ◽  
Vol 13 (1) ◽  
pp. 235-244 ◽  
Author(s):  
Mario Luiz Conte da Frota Junior ◽  
Renata Biegelmeyer da Silva ◽  
Beatriz Mothes ◽  
Amelia Teresinha Henriques ◽  
Jose Claudio Fonseca Moreira

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 298
Author(s):  
Despoina Konstantinou ◽  
Rafael V. Popin ◽  
David P. Fewer ◽  
Kaarina Sivonen ◽  
Spyros Gkelis

Sponges form symbiotic relationships with diverse and abundant microbial communities. Cyanobacteria are among the most important members of the microbial communities that are associated with sponges. Here, we performed a genus-wide comparative genomic analysis of the newly described marine benthic cyanobacterial genus Leptothoe (Synechococcales). We obtained draft genomes from Le. kymatousa TAU-MAC 1615 and Le. spongobia TAU-MAC 1115, isolated from marine sponges. We identified five additional Leptothoe genomes, host-associated or free-living, using a phylogenomic approach, and the comparison of all genomes showed that the sponge-associated strains display features of a symbiotic lifestyle. Le. kymatousa and Le. spongobia have undergone genome reduction; they harbored considerably fewer genes encoding for (i) cofactors, vitamins, prosthetic groups, pigments, proteins, and amino acid biosynthesis; (ii) DNA repair; (iii) antioxidant enzymes; and (iv) biosynthesis of capsular and extracellular polysaccharides. They have also lost several genes related to chemotaxis and motility. Eukaryotic-like proteins, such as ankyrin repeats, playing important roles in sponge-symbiont interactions, were identified in sponge-associated Leptothoe genomes. The sponge-associated Leptothoe stains harbored biosynthetic gene clusters encoding novel natural products despite genome reduction. Comparisons of the biosynthetic capacities of Leptothoe with chemically rich cyanobacteria revealed that Leptothoe is another promising marine cyanobacterium for the biosynthesis of novel natural products.


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