Phenolic derivatives from Ruprechtia polystachya and their inhibitory activities on the glucose-6-phosphatase system

Two new compounds, 5-methyl-2-(2-methylbutanoyl)phloroglucinol 1-O-(6-O-β-D-apiofuranosyl)-β-D-glucopyranoside (1) and trans-2,3-dihydrokaempferol 3-O-(4-O-sulfo)-α-L-arabinopyranoside (2), together with 14 known flavonoids, trans-dihydrokaempferol 3-O-α-L-arabinopyranoside (3), trans-taxifolin 3-O-α-L-arabinofuranoside (4), quercetin 3-O-α-L-rhamnopyranoside (5), quercetin 3'-O-α-L-arabinofuranoside (6), catechin 3-O-α-L-rhamnopyranoside (7), trans-taxifolin 3-O-α-L-arabinopyranoside (8), cis-dihydrokaempferol 3-O-α-L-arabinopyranoside (9), catechin (10), myricetin 3-O-α-L-rhamnopyranoside (11), quercetin 3-O-α-L-arabinopyranoside (12), quercetin 3-O-α-L-arabinofuranoside (13), quercetin 3-O-(3″-galloyl)-α-L-rhamnopyranoside (14), quercetin 3-O-(2″-galloyl)-α-L-rhamnopyranoside (15), and epicatechin 3-O-gallate (16), were isolated from the leaves of Ruprechtia polystachya Griseb. (Polygonaceae). Their structures were established on the basis of extensive 1D- and 2D-NMR experiments as well as MS analyses. All compounds, except 1, showed inhibition of the enzyme glucose-6-phosphatase in intact microsomes.     

Antiviral activity of 3,4’-dihydroxyflavone on influenza a virus

Influenza virus infection causes thousands of deaths and millions of hospitalizations worldwide every year and the emergence of resistance to anti-influenza drugs has prompted scientists to seek new natural antiviral materials. In this study, we screened 13 different flavonoids from various flavonoid groups to identify the most potent antiviral flavonoid against human influenza A/PR/8/34 (H1N1). The 3-hydroxyl group flavonoids, including 3,2?dihydroxyflavone (3,2?DHF) and 3,4?dihydroxyflavone (3,4?DHF), showed potent anti-influenza activity. They inhibited viral neuraminidase activity and viral adsorption onto cells. To confirm the anti-influenza activity of these flavonoids, we used an in vivo mouse model. In mice infected with human influenza, oral administration of 3,4?DHF significantly decreased virus titers and pathological changes in the lung and reduced body weight loss and death. Our data suggest that 3-hydroxyl group flavonoids, particularly 3,4?DHF, have potent antiviral activity against human influenza A/PR/8/34 (H1N1) in vitro and in vivo. Further clinical studies are needed to investigate the therapeutic and prophylactic potential of the 3-hydroxyl group flavonoids in treating influenza pandemics.     

半卧狗娃花中的黄酮类化合物

从半卧狗娃花(Heteropappus semiprost Griers)全草的乙醇提取物中分离并鉴定了7个黄酮类化合物,通过波谱分析及化学方法鉴定其结构为:3′,4′,5,7-四羟基黄酮(1),3′-甲氧基槲皮素(2),槲皮素-3-O-α-L-吡喃鼠李糖甙(3),槲皮素-3-O-β-D-吡喃半乳糖甙(4),异鼠李亭-3-O-β-D-吡喃半乳糖甙(5),槲皮素-3-O-α-L-吡喃鼠李糖(1→6)-β-D-吡喃葡萄糖甙(6),异鼠李亭-3-O-α-L-吡喃鼠李糖(1→6)-β-D-吡喃葡萄糖甙(7),其中化合物1~5为首次从本属植物中分离得到。     

Microwave assisted synthesis and anti-influenza virus activity of 1-adamantyl substituted N-(1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide derivatives

A microwave-assisted three-component one-pot cyclocondensation method was applied for the synthesis of novel N-(1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide compounds carrying an adamantyl moiety. The structures of the compounds were confirmed by spectral and elemental analysis. All compounds were evaluated for antiviral activity against influenza A (H1N1 and H3N2) and influenza B virus in MDCK cell cultures. The compounds displayed a confined structure-activity relationship. The N-(2,8-dimethyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)adamantane-1-carboxamide 3b was the most potent inhibitor [antiviral EC₅₀: 1.4 μM against influenza A/H3N2 virus]. Its strong inhibitory effect in a virus hemolysis assay supports that 3b acts as an influenza virus fusion inhibitor by preventing the conformational change of the influenza virus hemagglutinin at low pH.     

Triple Combination of Amantadine,Ribavirin, and Oseltamivir Is Highly Active and Synergistic against Drug Resistant Influenza Virus Strains In Vitro

The rapid emergence and subsequent spread of the novel 2009 Influenza A/H1N1 virus (2009 H1N1) has prompted the World Health Organization to declare the first pandemic of the 21^st century, highlighting the threat of influenza to public health and healthcare systems. Widespread resistance to both classes of influenza antivirals (adamantanes and neuraminidase inhibitors) occurs in both pandemic and seasonal viruses, rendering these drugs to be of marginal utility in the treatment modality. Worldwide, virtually all 2009 H1N1 and seasonal H3N2 strains are resistant to the adamantanes (rimantadine and amantadine), and the majority of seasonal H1N1 strains are resistant to oseltamivir, the most widely prescribed neuraminidase inhibitor (NAI). To address the need for more effective therapy, we evaluated the in vitro activity of a triple combination antiviral drug (TCAD) regimen composed of drugs with different mechanisms of action against drug-resistant seasonal and 2009 H1N1 influenza viruses. Amantadine, ribavirin, and oseltamivir, alone and in combination, were tested against amantadine- and oseltamivir-resistant influenza A viruses using an in vitro infection model in MDCK cells. Our data show that the triple combination was highly synergistic against drug-resistant viruses, and the synergy of the triple combination was significantly greater than the synergy of any double combination tested (P<0.05), including the combination of two NAIs. Surprisingly, amantadine and oseltamivir contributed to the antiviral activity of the TCAD regimen against amantadine- and oseltamivir-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that were clinically achievable. Our data demonstrate that the TCAD regimen composed of amantadine, ribavirin, and oseltamivir is highly synergistic against resistant viruses, including 2009 H1N1. The TCAD regimen overcomes baseline drug resistance to both classes of approved influenza antivirals, and thus may represent a highly active antiviral therapy for seasonal and pandemic influenza.     

Antiviral Effect of Methylated Flavonol Isorhamnetin against Influenza

Influenza is an infectious respiratory disease with frequent seasonal epidemics that causes a high rate of mortality and morbidity in humans, poultry, and animals. Influenza is a serious economic concern due to the costly countermeasures it necessitates. In this study, we compared the antiviral activities of several flavonols and other flavonoids with similar, but distinct, hydroxyl or methyl substitution patterns at the 3, 3′, and 4′ positions of the 15-carbon flavonoid skeleton, and found that the strongest antiviral effect was induced by isorhamnetin. Similar to quercetin and kaempferol, isorhamnetin possesses a hydroxyl group on the C ring, but it has a 3′-methyl group on the B ring that is absent in quercetin and kaempferol. Co-treatment and pre-treatment with isorhamnetin produced a strong antiviral effect against the influenza virus A/PR/08/34(H1N1). However, isorhamnetin showed the most potent antiviral potency when administered after viral exposure (post-treatment method) in vitro. Isorhamnetin treatment reduced virus-induced ROS generation and blocked cytoplasmic lysosome acidification and the lipidation of microtubule associated protein1 light chain 3-B (LC3B). Oral administration of isorhamnetin in mice infected with the influenza A virus significantly decreased lung virus titer by 2 folds, increased the survival rate which ranged from 70–80%, and decreased body weight loss by 25%. In addition, isorhamnetin decreased the virus titer in ovo using embryonated chicken eggs. The structure-activity relationship (SAR) of isorhamnetin could explain its strong anti-influenza virus potency; the methyl group located on the B ring of isorhamnetin may contribute to its strong antiviral potency against influenza virus in comparison with other flavonoids.     

Novel Pandemic Influenza A(H1N1) Viruses Are Potently Inhibited by DAS181, a Sialidase Fusion Protein

Background

The recent emergence of a novel pandemic influenza A(H1N1) strain in humans exemplifies the rapid and unpredictable nature of influenza virus evolution and the need for effective therapeutics and vaccines to control such outbreaks. However, resistance to antivirals can be a formidable problem as evidenced by the currently widespread oseltamivir- and adamantane-resistant seasonal influenza A viruses (IFV). Additional antiviral approaches with novel mechanisms of action are needed to combat novel and resistant influenza strains. DAS181 (Fludase™) is a sialidase fusion protein in early clinical development with in vitro and in vivo preclinical activity against a variety of seasonal influenza strains and highly pathogenic avian influenza strains (A/H5N1). Here, we use in vitro, ex vivo, and in vivo models to evaluate the activity of DAS181 against several pandemic influenza A(H1N1) viruses.

Methods and Findings

The activity of DAS181 against several pandemic influenza A(H1N1) virus isolates was examined in MDCK cells, differentiated primary human respiratory tract culture, ex-vivo human bronchi tissue and mice. DAS181 efficiently inhibited viral replication in each of these models and against all tested pandemic influenza A(H1N1) strains. DAS181 treatment also protected mice from pandemic influenza A(H1N1)-induced pathogenesis. Furthermore, DAS181 antiviral activity against pandemic influenza A(H1N1) strains was comparable to that observed against seasonal influenza virus including the H274Y oseltamivir-resistant influenza virus.

Conclusions

The sialidase fusion protein DAS181 exhibits potent inhibitory activity against pandemic influenza A(H1N1) viruses. As inhibition was also observed with oseltamivir-resistant IFV (H274Y), DAS181 may be active against the antigenically novel pandemic influenza A(H1N1) virus should it acquire the H274Y mutation. Based on these and previous results demonstrating DAS181 broad-spectrum anti-IFV activity, DAS181 represents a potential therapeutic agent for prevention and treatment of infections by both emerging and seasonal strains of IFV.     

Antiviral activity of an aqueous extract derived from Aloe arborescens Mill. against a broad panel of viruses causing infections of the upper respiratory tract

BackgroundA number of antiviral therapies have evolved that may be effectively administered to treat respiratory viral diseases. But these therapies are very often of limited efficacy or have severe side effects. Therefore there is great interest in developing new efficacious and safe antiviral compounds e.g. based on the identification of compounds of herbal origin.HypothesisSince an aqueous extract of Aloe arborescens Mill. shows antiviral activity against viruses causing infections of the upper respiratory tract in vitro we hypothesised that a product containing it such as Biaron C^® could have an antiviral activity too.Study designAntiviral activity of Bioaron C^®, an herbal medicinal product consisting of an aqueous extract of Aloe arborescens Mill., Vitamin C, and Aronia melanocarpa Elliot. succus, added as an excipient, was tested in vitro against a broad panel of viruses involved in upper respiratory tract infections.MethodsThese studies included human adenovirus and several RNA viruses and were performed either with plaque reduction assays or with tests for the detection of a virus-caused cytopathic effect.ResultsOur studies demonstrated an impressive activity of Bioaron C^® against members of the orthomyxoviridae – influenza A and influenza B viruses. Replication of both analysed influenza A virus strains – H1N1 and H3N2 – as well as replication of two analysed influenza B viruses – strains Yamagatal and Beiying – was significantly reduced after addition of Bioaron C^® to the infected cell cultures. In contrast antiviral activity of Bioaron C^® against other RNA viruses showed a heterogeneous pattern. Bioaron C^® inhibited the replication of human rhinovirus and coxsackievirus, both viruses belonging to the family of picornaviridae and both representing non-enveloped RNA viruses. In vitro infections with respiratory syncytial virus and parainfluenza virus, both belonging to the paramyxoviridae, were only poorly blocked by the test substance. No antiviral activity of Bioaron C^® was detected against adenovirus – a non-enveloped DNA virus.ConclusionsThese results represent the first proof of a selective antiviral activity of Bioaron C^® against influenza viruses and create basis for further analyses of type and molecular mechanisms of the antiviral activity of this herbal medicine.     

Inhibition of Influenza A Virus Infection In Vitro by Peptides Designed In Silico

Influenza A viruses are enveloped, segmented negative single-stranded RNA viruses, capable of causing severe human respiratory infections. Currently, only two types of drugs are used to treat influenza A infections, the M2 H⁺ ion channel blockers (amantadine and rimantadine) and the neuraminidase inhibitors (NAI) (oseltamivir and zanamivir). Moreover, the emergence of drug-resistant influenza A virus strains has emphasized the need to develop new antiviral agents to complement or replace the existing drugs. Influenza A virus has on the surface a glycoprotein named hemagglutinin (HA) which due to its important role in the initial stage of infection: receptor binding and fusion activities of viral and endosomal membranes, is a potential target for new antiviral drugs. In this work we designed nine peptides using several bioinformatics tools. These peptides were derived from the HA1 and HA2 subunits of influenza A HA with the aim to inhibit influenza A virus infection. The peptides were synthetized and their antiviral activity was tested in vitro against several influenza A viral strains: Puerto Rico/916/34 (H1N1), (H1N1)pdm09, swine (H1N1) and avian (H5N2). We found these peptides were able to inhibit the influenza A viral strains tested, without showing any cytotoxic effect. By docking studies we found evidence that all the peptides were capable to bind to the viral HA, principally to important regions on the viral HA stalk, thus could prevent the HA conformational changes required to carry out its membranes fusion activity.     

Evaluation of cytotoxicity and antiviral activity of Rhazya stricta Decne leaves extract against influenza A/PR/8/34 (H1N1)

Influenza viruses have developed resistance to the current classes of drugs, which means they could eventually become more virulent and cause more mortality and hospitalization. Our study aims to investigate the antiviral activity of Rhazya stricta Decne leaves extract in vitro and search for new promising drugs from R. stricta identified compounds in silico. The study was performed in vitro by utilizing Madin-Darby Canine Kidney cell line (MDCK) as a substrate for the influenza virus and estimating the inhibition performance of the plant leaves extract. Additionally, in silico screening was conducted to explore the antiviral activity of R. stricta phytochemicals. We investigated the cytotoxicity of R. stricta leaves extract and its antiviral activity against influenza virus (A/Puerto Rico/8/34 (H1N1)) using the MTT assay. The mode of action of the plant leaves extract during the viral life cycle was tested using time-of-addition assay. In silico analyses were performed, including molecular docking, drug-likeness analysis, and toxicity risk assessment, to state the leading compounds to be developed into an anti-influenza virus drug. The 50% cytotoxicity concentration of the leaves extract was CC50: 184.6 µg/mL, and the 50% inhibition concentration was CI50: 19.71 µg\mL. The time of addition assay revealed that R. stricta leaves extract exerted its activity in the late step of the influenza virus replication cycle. In comparison to Oseltamivir, the leading compounds showed better binding affinity and can be developed into oral drugs with low toxicity risk. Isolation and purification of the leading compounds and testing their antiviral activity in vitro and in vivo are required.     

Benzophenone C-glucosides and gallotannins from mango tree stem bark with broad-spectrum anti-viral activity

The high mutation rate of RNA viruses has resulted in limitation of vaccine effectiveness and increased emergence of drug-resistant viruses. New effective antivirals are therefore needed to control of the highly mutative RNA viruses. The n-butanol fraction of the stem bark of Mangifera indica exhibited inhibitory activity against influenza neuraminidase (NA) and coxsackie virus 3C protease. Bioassay guided phytochemical study of M. indica stem bark afforded two new compounds including one benzophenone C-glycoside (4) and one xanthone dimer (7), together with eleven known compounds. The structures of these isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Anti-influenza and anti-coxsackie virus activities were evaluated by determining the inhibition of anti-influenza neuraminidase (NA) from pandemic A/RI/5+/1957 H2N2 influenza A virus and inhibition of coxsackie B3 virus 3C protease, respectively. The highest anti-influenza activity was observed for compounds 8 and 9 with IC₅₀ values of 11.9 and 9.2 μM, respectively. Compounds 8 and 9 were even more potent against coxsackie B3 virus 3C protease, with IC₅₀ values of 1.1 and 2.0 μM, respectively. Compounds 8 and 9 showed weak cytotoxic effect against human hepatocellular carcinoma and human epithelial carcinoma cell lines through MTT assay.     

Three new benzophenone glycosides with MAO-A inhibitory activity from Hypericum thasium Griseb.

Purification of n-BuOH fraction from 80% ethanol extract of Hypericum thasium Griseb. resulted in the isolation of three new compounds 3′,4,5′-trihydroxy-6-methoxy-2-O-α-l-arabinosylbenzophenone (1), 3′,4,5′,6-tetrahydroxy-2-O-α-l-arabinosylbenzophenone (2), and 3′,4-dihydroxy-5′-methoxy-2-O-α-l-arabinosyl-6-O-β-d-xylosylbenzophenone (3) along with a known flavonoid glycoside quercetin-3-O-α-l-arabinofuranoside (4). The structures of the new compounds were elucidated by 1D and 2D NMR analysis as well as HRESIMS. The isolated compounds (1–4), as well as quercetin, and kaempferol previously isolated from EtOAc fraction were screened against MAO-A inhibitory activity. When tested against the MAO-A quercetin and kaempferol displayed IC₅₀ values of 19.6, and 17.5 μM, respectively. The IC₅₀ values for MAO-A inhibition by compounds (1–4) were 310.3, 111.2, 726.0, and 534.1 μM, respectively. Standard inhibitor (clorgyline) exhibited MAO-A inhibition with an IC₅₀ value of 0.5 μM.     

Broad-spectrum antiviral effect of Agrimonia pilosa extract on influenza viruses

Influenza virus continues to emerge and re-emerge, posing new threats for humans. Here we tested various Korean medicinal plant extracts for potential antiviral activity against influenza viruses. Among them, an extract of Agrimonia pilosa was shown to be highly effective against all three subtypes of human influenza viruses including H1N1 and H3N2 influenza A subtypes and influenza B virus. The EC₅₀ value against influenza A virus, as tested by the plaque reduction assay on MDCK cells, was 14–23 μg/ml. The extract also exhibited a virucidal effect at a concentration of 160–570 ng/ml against influenza A and B viruses when the viruses were treated with the extract prior to plaque assay. In addition, when tested in embryonated chicken eggs the extract exhibited a strong inhibitory effect in ovo on the H9N2 avian influenza virus at a concentration of 280 ng/ml. Quantitative RT-PCR analysis data showed that the extract, to some degree, suppressed viral RNA synthesis in MDCK cells. HI and inhibition of neuraminidase were observed only at high concentrations of the extract. And yet, the extract's antiviral activity required direct contact between it and the virus, suggesting that its antiviral action is mediated by the viral membrane, but does not involve the two major surface antigens, HA and NA, of the virus. The broad-spectrum antiviral activity of Agrimonia pilosa extract on various subtypes of influenza viruses merits further investigation as it may provide a means of managing avian influenza infections in poultry farms and potential avian-human transmission.     

Protection from the 2009 H1N1 Pandemic Influenza by an Antibody from Combinatorial Survivor-Based Libraries

Influenza viruses elude immune responses and antiviral chemotherapeutics through genetic drift and reassortment. As a result, the development of new strategies that attack a highly conserved viral function to prevent and/or treat influenza infection is being pursued. Such novel broadly acting antiviral therapies would be less susceptible to virus escape and provide a long lasting solution to the evolving virus challenge. Here we report the in vitro and in vivo activity of a human monoclonal antibody (A06) against two isolates of the 2009 H1N1 pandemic influenza virus. This antibody, which was obtained from a combinatorial library derived from a survivor of highly pathogenic H5N1 infection, neutralizes H5N1, seasonal H1N1 and 2009 “Swine” H1N1 pandemic influenza in vitro with similar potency and is capable of preventing and treating 2009 H1N1 influenza infection in murine models of disease. These results demonstrate broad activity of the A06 antibody and its utility as an anti-influenza treatment option, even against newly evolved influenza strains to which there is limited immunity in the general population.     

Synthesis and antiviral activity of substituted quercetins

Influenza viruses are important pathogens that cause respiratory infections in humans and animals. In addition to vaccination, antiviral drugs against influenza virus play a significant role in controlling viral infections by reducing disease progression and virus transmission. Plant derived polyphenols are associated with antioxidant activity, anti-carcinogenic, and cardio- and neuro-protective actions. Some polyphenols, such as resveratrol and epigallocatechin gallate (EGCG), showed significant anti-influenza activity in vitro and/or in vivo. Recently we showed that quercetin and isoquercetin (quercetin-3-β-d-glucoside), a glucoside form of quercetin, significantly reduced the replication of influenza viruses in vitro and in vivo (isoquercetin). The antiviral effects of isoquercetin were greater than that of quercetin with lower IC(50) values and higher in vitro therapeutic index. Thus, we investigated the synthesis and antiviral activities of various quercetin derivatives with substitution of C3, C3', and C5 hydroxyl functions with various phenolic ester, alkoxy, and aminoalkoxy moieties. Among newly synthesized compounds, quercetin-3-gallate which is structurally related to EGCG showed comparable antiviral activity against influenza virus (porcine H1N1 strain) to that of EGCG with improved in vitro therapeutic index.     

Molecular docking of selected phytocompounds with H1N1 Proteins

The H1N1 influenza virus is a serious threat to human population. Oseltamivir and Zanamivir are known antiviral drugs for swine flu with observed side effects. These drugs are viral neuraminidase and hemagglutinin inhibitor prevents early virus multiplication by blocking sialic acid cleavage on host cells. Therefore, it is of interest to identify naturally occurring novel compounds to control viral growth. Thus, H1N1 proteins (neuraminidase and hemagglutinin) were screened with phytocompounds isolated from Tulsi plant (Ocimum sanctum L.) using molecular docking tools. This identified Apigenin as an alternative to Oseltamivir and Zanamivir with improved predicted binding properties. Hence, it is of interest to consider this compound for further in vitro and in vivo evaluation.     

5-Chloro-2-thiophenyl-1,2,3-triazolylmethyldihydroquinolines as dual inhibitors of Mycobacterium tuberculosis and influenza virus: Synthesis and evaluation

This study describes synthesis and evaluation of novel 5-Chloro-2-thiophenyl-1,2,3-triazolylmethyldihydroquinolines 7a-o as dual inhibitors of Mycobacterium tuberculosis and influenza virus. Huisgen’s [3+2] dipolar cycloaddition of 6-(azidomethyl)-5-chloro-2-(thiophen-2-yl)-7,8-dihydroquinoline 5 with various alkynes 6a-o using sodium ascorbate and copper sulphate gave new dihydroquinoline-1,2,3-triazoles 7a-o in good to excellent yields. The new compounds were evaluated for in vitro antimycobacterial against M. tuberculosis H37Rv (Mtb) and antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1). Among the fifteen new analogs, compounds 7a (MIC: 3.12 µg/mL), 7j and 7k (MIC: 6.25 µg/mL) were identified as potent antitubercular agents. The virus-inhibiting activity of all the fifteen compounds was found to be moderate, and among them the compound 7l, bearing thiophene moiety appeared the most active with good selectivity index (IC₅₀ = 19.5 µg/mL; SI = 15). The results presented here will help developing newer dual inhibitors of tuberculosis and influenza virus.     

Synthesis of camphecene derivatives using click chemistry methodology and study of their antiviral activity

A series of seventeen tetrazole derivatives of 1,7,7-trimethyl-[2.2.1]bicycloheptane were synthesized using click chemistry methodology and characterized by spectral data. Studies of cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells of the compounds obtained were performed. The structure-activity relationship analysis suggests that to possess virus-inhibiting activity, the compounds of this group should bear oxygen atom with a short linker (C2-C4), either as a hydroxyl group (18, 19, 29), keto-group (21) or as a part of a heterocycle (24). These compounds demonstrated low cytotoxicity along with high anti-viral activity.     

Tannins from Hamamelis virginiana Bark Extract: Characterization and Improvement of the Antiviral Efficacy against Influenza A Virus and Human Papillomavirus

Antiviral activity has been demonstrated for different tannin-rich plant extracts. Since tannins of different classes and molecular weights are often found together in plant extracts and may differ in their antiviral activity, we have compared the effect against influenza A virus (IAV) of Hamamelis virginiana L. bark extract, fractions enriched in tannins of different molecular weights and individual tannins of defined structures, including pseudotannins. We demonstrate antiviral activity of the bark extract against different IAV strains, including the recently emerged H7N9, and show for the first time that a tannin-rich extract inhibits human papillomavirus (HPV) type 16 infection. As the best performing antiviral candidate, we identified a highly potent fraction against both IAV and HPV, enriched in high molecular weight condensed tannins by ultrafiltration, a simple, reproducible and easily upscalable method. This ultrafiltration concentrate and the bark extract inhibited early and, to a minor extent, later steps in the IAV life cycle and tannin-dependently inhibited HPV attachment. We observed interesting mechanistic differences between tannin structures: High molecular weight tannin containing extracts and tannic acid (1702 g/mol) inhibited both IAV receptor binding and neuraminidase activity. In contrast, low molecular weight compounds (<500 g/mol) such as gallic acid, epigallocatechin gallate or hamamelitannin inhibited neuraminidase but not hemagglutination. Average molecular weight of the compounds seemed to positively correlate with receptor binding (but not neuraminidase) inhibition. In general, neuraminidase inhibition seemed to contribute little to the antiviral activity. Importantly, antiviral use of the ultrafiltration fraction enriched in high molecular weight condensed tannins and, to a lesser extent, the unfractionated bark extract was preferable over individual isolated compounds. These results are of interest for developing and improving plant-based antivirals.