Anti-influenza Virus Activity Research Articles

The high-throughput solid-phase extraction of cis-cyclo(L-Leu-L-Pro) and cis-cyclo(L-Phe-L-Pro) from Lactobacillus plantarum demonstrates efficacy against multidrug-resistant bacteria and influenza A (H3N2) virus

Introduction: 2,5-diketopiperazines are the simplest forms of cyclic dipeptides (CDPs) and have diverse frameworks with chiral side chains that are useful for drug development. Previous research has investigated the antimicrobial properties of proline-linked CDPs and their combinations in the culture filtrate (CF) of Lactobacillus plantarum LBP-K10 using anion exchange chromatography (AEC). However, the quantity of CDPs showcasing notable anti-influenza virus activity derived from AECs was generally lower than those originating from Lactobacillus CF.Methods: To address this issue, the study aims to propose a more efficient method for isolating CDPs and to introduce the antiviral combinations of CDPs obtained using a new method. The study employed a novel technique entailing high-throughput C18-based solid-phase extraction with a methanol gradient (MeSPE). The MeSPE method involved increasing the methanol concentration from 5% to 50% in 5% increments.Results: The methanol SPE fractions (MeSPEfs) eluted with methanol concentrations between 35% and 45% evinced substantial efficacy in inhibiting the influenza A/H3N2 virus via plaque-forming assay. MeSPEf-45, the 45% MeSPEf, exhibited exceptional efficacy in preventing viral infections in Madin-Darby kidney cells, surpassing both individual CDPs and the entire set of MeSPEfs. To identify the specific antiviral components of MeSPEf-45, all MeSPEfs were further fractionated through preparative high-performance liquid chromatography (prep-HPLC). MeSPEf-45 fractions S8 and S11 presented the highest activity against multidrug-resistant bacteria and influenza A/H3N2 virus among all MeSPEfs, with 11 common fractions. Antiviral fractions S8 and S11 were identified as proline-based CDPs, specifically cis-cyclo(L-Leu-L-Pro) and cis-cyclo(L-Phe-L-Pro), using gas chromatography-mass spectrometry. The combination of MeSPEf-45 fractions S8 and S11 displayed superior antibacterial and anti-influenza virus effects compared to the individual fractions S8 and S11.Discussion: High-throughput MeSPE-derived MeSPEfs and subsequent HPLC-fractionated fractions presents an innovative approach to selectively purify large amounts of potent antimicrobial CDPs from bacterial CF. The findings also show the effectiveness of physiologically bioactive combinations that utilize fractions not containing CDP. This study provides the initial evidence demonstrating the antimicrobial properties of CDPs acquired through high-throughput SPE techniques.

Synthesis of Rupestonic Acid L-Ephedrine Derivatives with Preliminary In vitro Anti-influenza Viral Activity.

Influenza virus is a kind of RNA virus. Nowadays, the high incidence of influenza and the morbidity and mortality of epidemic influenza are substantial. It has been reported that one hundred million people in the world are infected with influenza viruses, and two hundred and fifty thousand to five hundred thousand people die from the flu per year. In 2021, the number of infected persons in China was reported to be 654,700, and 0.07% of the infected persons died. The flu has caused a serious threat to human survival. Although several drugs, such as Zanamivir, Oseltamivir, Peramivir, and Laninamivir, have been used in clinics for the treatment of the influenza virus, there are some shortcomings of these drugs. The strain of influenza H5N1 (avian influenza) has been found to resist the effective drug Oseltamivir. Thus, there is an urgent demand to discover new anti-influenza virus inhibitors to overcome the emergence of influenza antigens. This study aimed to develop new anti-influenza virus inhibitors based on the rupestonic acid parent core. The rupestonic acid L-ephedrine ester (A) and rupestonic acid L-ephedrine complex (B) were synthesized in this work for the development of anti-influenza virus inhibitors. The target compounds were synthesized using rupestonic acid and L-ephedrine as starting materials. Their structures were characterized by 1H NMR and 13C NMR, and the purity was determined by HPLC. Then, their preliminary in vitro anti-influenza activity was evaluated using Oseltamivir as a reference drug. The results showed that the synthesized rupestonic acid L-ephedrine derivatives A and B were more potent anti-influenza virus agents against the strains of A/PR/8/34 (H1N1) and A/FM/1/47 (H1N1) with the IC50 values of 51.0, 51.0 μM and 441.0, 441.0 μM, respectively, than that of rupestonic acid. By comparing the IC50 of compounds A and B, compound A can be regarded as a very promising lead compound for the development of anti-influenza inhibitors. The rupestonic acid L-ephedrine ester (A) and rupestonic acid L-ephedrine complex (B) were synthesized and characterized using 1H NMR and 13C NMR. Moreover, their purity was determined by HPLC. Both compounds A and B exhibited more potent activities against the strains of A/PR/8/34 (H1N1) and A/FM/1/47 (H1N1) than rupestonic acid. Compound A can be regarded as a very promising lead compound for the development of anti-influenza inhibitors. Based on these results, more rupestonic acid derivatives will be designed and synthesized in the future for the development of anti-influenza inhibitors.

Biotransformation of Patchouli Alcohol by Cladosporium cladosporioides and the Anti-Influenza Virus Activities of Biotransformation Products.

The biotransformation of patchouli alcohol by Cladosporium cladosporioides afforded 31 products, including 21 new ones (1-3, 5, 6, 8-14, and 17-25). Their structures were determined by extensive spectroscopic data analysis (1H and 13C NMR, HSQC, HMBC, 1H-1H COSY, ROESY, and HRESIMS), and the absolute configuration of compounds 1, 2, 8, 9, and 17 was determined by single-crystal X-ray diffraction using Cu Kα radiation. Structurally, compounds 21-24 were patchoulol-type norsesquiterpenoids without Me-12. Among them, a Δ3(4) double bond existed in compounds 21 and 22; a three-membered ring was formed between C-4, C-5, and C-6 in compound 23; an epoxy moiety appeared between C-3 and C-4 in compound 24. Furthermore, the biotransformation products 9, 10, 12, and 25 showed potent anti-influenza virus activity with EC50 values of 2.11, 7.94, 20.87, and 3.45 μM, respectively.

A Noble Extract of Pseudomonas sp. M20A4R8 Efficiently Controlling the Influenza Virus-Induced Cell Death.

Epidemic diseases that arise from infectious RNA viruses, particularly influenza viruses, pose a constant threat to the global economy and public health. Viral evolution has undermined the efficacy of acquired immunity from vaccines and the antiviral effects of FDA-approved drugs. As such, there is an urgent need to develop new antiviral lead agents. Natural compounds, owing to their historical validation of application and safety, have become a promising solution. In this light, a novel marine bacterium, Pseudomonas sp. M20A4R8, has been found to exhibit significant antiviral activity [half maximal inhibitory concentration (IC50) = 1.3 µg/mL, selectivity index (SI) = 919.4] against influenza virus A/Puerto Rico/8/34, surpassing the activity of chloroquine. The antiviral response via M20A4R8 extract was induced during post-entry stages of the influenza virus, indicating suitability for post-application after the establishment of viral infection. Furthermore, post-treatment with M20A4R8 extract protected the host from virus-induced apoptosis, suggesting its potential use in acute respiratory disease complexes resulting from immune effectors' overstimulation and autophagy-mediated self-apoptosis. The extract demonstrated an outstanding therapeutic index against influenza virus A/Wisconsin/15/2009 (IC50 = 8.1 µg/mL, SI = 146.2) and B/Florida/78/2015 Victoria lineage (IC50 = 3.5 µg/mL, SI = 343.8), indicating a broad anti-influenza virus activity with guaranteed safety and effectiveness. This study provides a new perspective on mechanisms for preventing a broad spectrum of viral infections through antiviral agents from novel and natural origins. Future studies on a single or combined compound from the extract hold promise, encouraging its use in preclinical challenge tests with various influenza virus strains.

Combination therapy of nitazoxanide with oseltamivir compared with oseltamivir in hospitalized patients with seasonal influenza.

Antiviral combinations have been proposed as treatment for influenza in order to increase the antiviral activity by action at different sites of action as well as obviate the emergence of drug resistance to the commonly used antiviral agents like oseltamivir. Nitazoxanide has been found to exhibit anti-influenza viral activity with clinical benefit in a previous study. We recruited 242 cases of SARI, among whon 67 were confirmed to have influenza viral infection. In a randomized blinded fashion, 34 patients received a combination of nitazoxanide and oseltamivir whereas 33 cases received oseltamivir alone. Clinical parameters were followed in both groups and the nasal swabs were re-tested on day 6 for influenza positivity and the cycle threshold (CT) values. No significant differences were observed in terms of time for resolution of fever, other symptoms, and SOFA scores. Nine patients succumbed during the course of the illness that included three in the oseltamivir group and six in the combination group. All but one of those who expired had an underlying co-morbid illness. Our preliminary data suggest that the addition of nitazoxanide does not improve outcomes in hospitalized patients with influenza. Larger studies are recommended for statistically robust conclusions.

Evaluation of the Antiviral Activity of Tabamide A and Its Structural Derivatives against Influenza Virus.

Influenza viruses cause severe endemic respiratory infections in both humans and animals worldwide. The emergence of drug-resistant viral strains requires the development of new influenza therapeutics. Tabamide A (TA0), a phenolic compound isolated from tobacco leaves, is known to have antiviral activity. We investigated whether synthetic TA0 and its derivatives exhibit anti-influenza virus activity. Analysis of structure-activity relationship revealed that two hydroxyl groups and a double bond between C7 and C8 in TA0 are crucial for maintaining its antiviral action. Among its derivatives, TA25 showed seven-fold higher activity than TA0. Administration of TA0 or TA25 effectively increased survival rate and reduced weight loss of virus-infected mice. TA25 appears to act early in the viral infection cycle by inhibiting viral mRNA synthesis on the template-negative strand. Thus, the anti-influenza virus activity of TA0 can be expanded by application of its synthetic derivatives, which may aid in the development of novel antiviral therapeutics.

Antiviral Activities of Some Traditional Medicinal Plants of Sri Lanka

Abstract: The aim of this article is to review the antiviral activity of plants traditionally used in indigenous medicine in Sri Lanka, their therapeutic potential, chemistry, and botany. Viral infections represent an increasing threat to humans worldwide. Conventional antiviral drugs are available against respiratory viruses. Naturally occurring antiviral activity of medicinal plants was used for centuries in the country’s rich traditional medicine system consisting of Ayurveda, Siddha, Unani, and Deshiya Chikitsa. Traditional physicians cure diseases, including those that originate from viruses, through herbal medicine. To complement this, about 1430 species representing 838 genera, equivalent to 45% of the entire flowering plant community, are considered medicinal. The present article attempts to review the essence of decades of discoveries on antiviral and related properties of 21 medicinal plants, Allium sativum L., Annona muricata L., Ardisia elliptica Thunb., Azadirachta indica A. Juss., Caesalpinia pulcherrima (L.) Sw., Coriandrum sativum L., Coscinium fenestratum (Gaertn.) Colebr., Hedyotis corymbosa (L.) Lam., Hemidesmus indicus (L.) R. Br., Justicia adhatoda L., Ocimum tenuiflorum L., Phyllanthus embilica L., Phyllanthus debilis Klein ex Willd., Piper longum L., Piper nigrum L., Solanum xanthocarpum Schrad & Wendl., Terminalia bellirica (Gaertn.) Roxb., Terminalia chebula Retz., Tinospora cordifolia (Wild) Miers., Vitex negundo L., Zingiber officinale Roscoe. Among the medicinal plants commonly used in Sri Lankan traditional medicine, Justicia adhatoda showed stronger anti-influenza virus activity, inhibiting virus attachment and replication, while Terminalia chebula consisting of chebulagic and chebulinic acids, demonstrated direct antiviral activity against sexually transmitted herpes simplex virus-2 (HSV-2).

Terpenoids from the Roots of Stellera chamaejasme (L.) and Their Bioactivities

An undescribed diterpene, stellerterpenoid A (1), and two undescribed sesquiterpenoids, stellerterpenoids B and C (2–3), together with six known compounds, prostratin (4) stelleraguaianone B (5), chamaejasnoid A (6), auranticanol L (7), wikstronone C (8), and oleodaphnone (9), were isolated from the roots of Stellera chamaejasme L. Their structures were elucidated by extensive spectroscopic data (1D, 2D NMR, IR, UV, and HR-ESI-MS). The absolute configuration of 1–3 was elucidated based on ECD calculation. Among them, stellerterpenoid A was a rare 13, 14-seco nortigliane diterpenoid and stellerterpenoid B was a guaiacane-type sesquiterpenoid with an unusual 1, 2-diketone moiety. The known stelleraguaianone B (5) exhibited moderate activity for suppressing NO production in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages cells with an IC50 value of 24.76 ± 0.4 μM. None of the compounds showed anti-influenza virus or anti-tumor activity in vitro.

Anti-Influenza Virus Activity of Citrullus lanatus var. citroides as a Functional Food: A Review.

Influenza is an acute respiratory illness caused by the influenza virus, in response to which vaccines and antiviral drugs are administered. In recent years, the antiviral effects of plants and foods have garnered attention. This review is the first to summarize the therapeutic properties of wild watermelon (Citrullus lanatus var. citroides) against influenza from a phytochemical viewpoint. Wild watermelon is a wild plant with significant potential as a therapeutic candidate in antiviral strategies, when focused on its multiple anti-influenza functionalities. Wild watermelon juice inhibits viral growth, entry, and replication. Hence, we highlight the possibility of utilizing wild watermelon for the prevention and treatment of influenza with stronger antiviral activity. Phytochemicals and phytoestrogen (polyphenol, flavonoids, and prenylated compounds) in wild watermelon juice contribute to this activity and inhibit various stages of viral replication, depending on the molecular structure. Wild plants and foods closely related to the original species contain many natural compounds such as phytochemicals, and exhibit various viral growth inhibitory effects. These natural products provide useful information for future antiviral strategies.

Anti-influenza virus activities and mechanism of antrafenine analogs

Antrafenine is a drug initially designed for anti-inflammation uses. In this work we have synthesized a library of its structural analogs and tested the anti-influenza activities. These analogs belong to a group of 2-(quinolin-4-yl)amino benzamides or 2-(quinolin-4-yl)amino benzoate derivatives. Best performers were identified, namely 12, 34, 41, with IC50 against A/WSN/33 (H1N1) of 5.53, 3.21 and 6.73 μM respectively. These chemicals were also effective against A/PR/8/34 (H1N1), A/HK/1/68 (H3N2) and B/Florida/04/2006 viruses. Time-of-addition study and minigenome luciferase reporter assay both supported that the compounds act on the ribonucleoprotein (RNP) components. Using 34 and 41 as representative compounds, we determined by microscale thermophoresis that this group of compounds bind to both PA C-terminal domain and the nucleoprotein (NP) which is the most abundant subunit of the RNP. Taken together, we have identified a new class of anti-influenza compounds with dual molecular targets and good potential to be further developed. ImportanceThe influenza viruses, especially influenza A and B subtypes, cause many deaths each year. The high mutation rate of the virus renders available therapeutics less effective with time. In this work we identify a new class of compounds, structurally similar to the anti-inflammation drug antrafenine, with good potency against influenza A strains. The IC50 of the best performers are within low micromolar range and thus have good potential for further development.

The Interferon-Induced Protein with Tetratricopeptide Repeats Repress Influenza Virus Infection by Inhibiting Viral RNA Synthesis.

Influenza A virus (IAV) is an eight-segment negative-sense RNA virus and is subjected to gene recombination between strains to form novel strains, which may lead to influenza pandemics. Seasonal influenza occurs annually and causes great losses in public healthcare. In this study, we examined the role of interferon-induced protein with tetratricopeptide repeats 1 and 2 (IFIT1 and IFIT2) in influenza virus infection. Knockdown of IFIT1 or IFIT2 using a lentiviral shRNA increased viral nucleoprotein (NP) and nonstructural protein 1 (NS1) protein levels, as well as progeny virus production in A/Puerto Rico/8/34 H1N1 (PR/8)-infected lung epithelial A549 cells. Overexpression of IFIT1 or IFIT2 reduced viral NP and NS1 RNA and protein levels in PR/8-infected HEK293 cells. Overexpression of IFIT1 or IFIT2 also inhibited influenza virus infection of various H1N1 strains, including PR/8, A/WSN/1933, A/California/07/2009 and A/Oklahoma/3052/2009, as determined by a viral reporter luciferase assay. Furthermore, knockdown of IFIT1 or IFIT2 increased while overexpression of IFIT1 or IFIT2 decreased viral RNA, complementary RNA, and mRNA levels of NP and NS1, as well as viral polymerase activities. Taken together, our results support that both IFIT1 and -2 have anti-influenza virus activities by inhibiting viral RNA synthesis.

Identification of Anti-Influenza A Compounds Inhibiting the Viral Non-Structural Protein 1 (NS1) Using a Type I Interferon-Driven Screening Strategy.

There is an urgent need to identify efficient antiviral compounds to combat existing and emerging RNA virus infections, particularly those related to seasonal and pandemic influenza outbreaks. While inhibitors of the influenza viral integral membrane proton channel protein (M2), neuraminidase (NA), and cap-dependent endonuclease are available, circulating influenza viruses acquire resistance over time. Thus, the need for the development of additional anti-influenza drugs with novel mechanisms of action exists. In the present study, a cell-based screening assay and a small molecule library were used to screen for activities that antagonized influenza A non-structural protein 1 (NS1), a highly conserved, multifunctional accessory protein that inhibits the type I interferon response against influenza. Two potential anti-influenza agents, compounds 157 and 164, were identified with anti-NS1 activity, resulting in the reduction of A/PR/8/34(H1N1) influenza A virus replication and the restoration of IFN-β expression in human lung epithelial A549 cells. A 3D pharmacophore modeling study of the active compounds provided a glimpse of the structural motifs that may contribute to anti-influenza virus activity. This screening approach is amenable to a broader analysis of small molecule compounds to inhibit other viral targets.

Bioassay guided isolation of caffeoylquinic acids from the leaves of Ilex pubescens Hook. et Arn. and investigation of their anti-influenza mechanism.

Ilex pubescens Hook. et Arn. (Maodongqing, MDQ) is a common herbal tea ingredient in Southern China for heat clearance and anti-inflammation. Our preliminary screening showed that 50% ethanol extract of its leaves has anti-influenza virus activity. In this report, we proceed to identify the active components and clarify the related anti-influenza mechanisms. We aim to isolate and identify the anti-influenza virus phytochemicals from the extract of the MDQ leaves, and study their anti-influenza virus mechanism. Plaque reduction assay was used to test the anti-influenza virus activity of fractions and compounds. Neuraminidase inhibitory assay was used to confirm the target protein. Molecular docking and reverse genetics were used to confirm the acting site of caffeoylquinic acids (CQAs) on viral neuraminidase. Eight CQAs, 3,5-di-O-caffeoylquinic acid methyl ester (Me 3,5-DCQA), 3,4-di-O-caffeoylquinic acid methyl ester (Me 3,4-DCQA), 3,4,5-tri-O-caffeoylquinic acid methyl ester (Me 3,4,5-TCQA), 3,4,5-tri-O-caffeoylquinic acid (3,4,5-TCQA), 4,5-di-O-caffeoylquinic acid (4,5-DCQA), 3,5-di-O-caffeoylquinic acid (3,5-DCQA), 3,4-di-O-caffeoylquinic acid (3,4-DCQA), and 3,5-di-O-caffeoyl-epi-quinic acid (3,5-epi-DCQA) were identified from the MDQ leaves, in which Me 3,5-DCQA, 3,4,5-TCQA and 3,5-epi-DCQA were isolated for the first time. All these eight compounds were found to inhibit neuraminidase (NA) of influenza A virus. The results of molecular docking and reverse genetics indicated that 3,4,5-TCQA interacted with Tyr100, Gln412 and Arg419 of influenza NA, and a novel NA binding groove was found. Eight CQAs isolated from the leaves of MDQ were found to inhibit influenza A virus. 3,4,5-TCQA was found to interact with Tyr100, Gln412 and Arg419 of influenza NA. This study provided scientific evidence on the use of MDQ for treating influenza virus infection, and laid the foundation for the development of CQA derivatives as potential antiviral agents.

Design, Synthesis, Biological Evaluation, and Molecular Dynamics Simulation of Influenza Polymerase PB2 Inhibitors

The PB2 subunit of the influenza RNA-dependent RNA polymerase (RdRp) has been identified as a promising target for the treatment of influenza. To expand the chemical space of the known influenza polymerase PB2 inhibitor-pimodivir (formerly VX-787) and improve its pharmacokinetic profile, two pimodivir analogs containing 2,3-dihydro-imidazopyridine fragment (comp. I and comp. II) were designed, synthesized, and evaluated for anti-influenza virus activity. In the cytopathic effect (CPE) inhibition assay, comp. I and comp. II showed IC50 values of 0.07 and 0.09 μM for A/Puerto Rico/8/34 (H1N1) and 0.04 and 0.07 μM for A/Hong Kong/8/68 (H3N2), respectively. Protein-binding affinity assay results showed a concentration-dependent association and dissociation pattern, with KD values of 1.398 and 1.670 μM, respectively. In vitro metabolic stability assays showed that comp. I and comp. II exhibited good stability to liver microsomes and considerably less sensitivity to aldehyde oxidase compared to pimodivir. The binding modes of comp. I and comp. II were similar to those of VX-787; however, comp. I and comp. II had lower structural adaptability to PB2 than VX-787. Our results provide helpful information regarding the structure-activity relationship for the design of novel PB2 inhibitors and a reference for the development of drugs containing 2,3-dihydro-imidazopyridine fragments.

Daidzein phosphorylates and activates 5-lipoxygenase via the MEK/ERK pathway: a mechanism for inducing the production of 5-lipoxygenase metabolite that inhibit influenza virus intracellular replication

We previously reported that the soy isoflavone daidzein (Dz) suppresses the intracellular replication of influenza virus and that arachidonic acid-derived oxidation product via lipid oxidase 5-lipoxygenase (5-LOX) is involved in its antiviral effect. The activation of 5-LOX by Dz triggers anti-influenza activity; however, the mechanism of activation of 5-LOX remains unclear. Therefore, in this study, we aimed to clarify the activation mechanism using human monocyte-derived THP-1 cells differentiated using phorbol 12-myristate 13-acetate. THP-1 cells expressed 5-LOX endogenously and Dz did not induce 5-LOX expression. However, 8 h after treatment with Dz, the amount of 5-hydroxyeicosatetraenoic acid (5-HETE), an arachidonic acid oxidation product via 5-LOX, increased significantly suggesting that the enzyme is activated regardless of changes in 5-LOX protein levels. Intracellular Ca2+ content, ATP concentration, 5-LOX protein phosphorylation, and 5-LOX intracellular localization are known 5-LOX activation factors. The intracellular Ca2+ and ATP concentrations were not affected by Dz treatment. The enzymatic activity of 5-LOX is regulated by the phosphorylation of three serine residues and four tyrosine residues. Pretreatment with inhibitors of each kinase revealed that Dz-induced 5-HETE production was suppressed by the MEK/ERK inhibitor. 5-LOX in which the Ser663 residue was phosphorylated was found to be increased in the nuclear fraction of Dz-treated THP-1 cells. Furthermore, immunocytochemistry showed that 5-LOX translocates to the nuclear envelope following Dz treatment. These results indicate that Dz activates 5-LOX by phosphorylating Ser663 via the MEK/ERK pathway. Thus, these results demonstrate that Dz exerts anti-influenza virus activity via the MEK/ERK signal transduction pathway.

1H NMR-Based Biochemometric Analysis of Morus alba Extracts toward a Multipotent Herbal Anti-Infective

Mulberry Diels-Alder-type adducts (MDAAs) derived from the white mulberry tree were discovered recently as dual inhibitors of influenza viruses and pneumococci. For the development of a natural product based remedy for respiratory infections, the aim was to (i) identify the most prolific natural source of MDAAs, (ii) develop a protocol to maximize the content of MDAAs in Morus alba extracts, (iii) unravel constituents with the highest anti-infective potential within multicomponent mixtures, and (iv) select and characterize a hit extract as a candidate for further studies. Validated quantitative UPLC-PDA analysis of seven MDAAs (1-7) revealed the root bark as the best starting material and pressurized liquid extraction (PLE) as the optimum technique for extraction. Extracts enriched in MDAAs of a total content above 20% exerted a potent dual anti-influenza virus and antipneumococcal activity. For a detailed analysis of the most bioactive chemical features and molecules within the extracts, 1H NMR-based heterocovariance analysis (HetCA) was used. According to the multivariate statistical analysis procedure conducted, MDAAs exclusively accounted for the in vitro anti-influenza viral effect. The anti-infective profile of one hit extract (MA60) investigated showed a good tolerance by lung cells (A549, Calu-3) and pronounced in vitro activities against influenza viruses, S. pneumoniae, S. aureus, and inflammation.

In Vitro Anti-Influenza Virus Activity of Non-Polar Primula veris subsp. veris Extract.

Medicinal plants have long been recognized as a tremendous source of candidate compounds for the development of pharmaceuticals, including anti-viral agents. Herein, we report the identification of anti-influenza virus activity in non-polar Primula veris L. subsp. veris extracts. We show that P. veris subsp. veris flower extracts, obtained using supercritical fluid or ultrasound-based extraction, possess virucidal/virus inactivation properties and confer prophylactic and therapeutic effects against influenza virus-induced cytolysis in vitro. By GC-MS and UPLC-HRMS analysis of non-polar P. veris subsp. veris extracts we identified terpenes, flavones, tocopherols, and other classes of phytochemicals with known or putative anti-influenza properties. In silico prediction of cellular functions and molecular pathways affected by these phytochemicals suggests putative effects on signal transduction, inflammasome, and cell death pathways that are relevant to influenza virus pathogenesis. Combining P. veris subsp. veris with extracts of medicinal plants with proven anti-influenza activity such as Echinacea purpurea (L.) Moench and Cistus creticus L. subsp. creticus achieves an impressive protective effect against infection by influenza virus H1N1 in vitro and reduced progeny virus production by infected cells. Collectively, these findings uncover a previously uncharted biological property of non-polar P. veris flower extracts that warrants further studies to assess clinical efficacy.

Two new compounds from the aerial parts of Elsholtzia densa

Two new compounds, named edensa acid ( 1 ), and edensaoside A ( 2 ), as well as twenty-nine known compounds ( 3–31 ) were isolated from the aerial parts of Elsholtzia densa Benth. The chemical structures of the new compounds were determined by spectrometric data interpretation using NMR, HRESIMS, IR and UV spectroscopy. In addition, all compounds were evaluated for their anti-influenza virus activities against A/WSN/33(H1N1). Among these, compounds 18 and 19 exhibited moderate anti-influenza virus activities with IC 50 values of 18.79 μ M and 59.87 μ M respectively. • Two new and twenty-nine known compounds were isolated from the aerial parts of Elsholtzia densa Benth. • Structures were elucidated by spectroscopic analysis. • Compounds were evaluated for their anti-influenza A virus activities.

The chemical constituents from Valeriana jatamansi and their anti-influenza virus and anti-inflammatory effects

Twenty-seven compounds, including six new iridoids, valeransins A−F ( 1 − 6 ), were isolated from the n -BuOH soluble fraction of Valeriana jatamansi . Structurally, compounds 1 and 2 are rare 8, 11-epoxy iridoids, and their absolute configuration was determined based on their experimental and calculated electronic circular dichroism (ECD) spectra. In addition, compounds 5 and 24 exhibited significant anti-influenza virus activities, with IC 50 values of 7.23 and 19.83 μM, respectively. Additionally, compound 24 showed inhibition of NO production stimulated by lipopolysaccharide in RAW 264.7 cells, with an IC 50 value of 27.22 μM. • Six new iridoids, valeransins A−F, were isolated from Valeriana jatamansi . • Valeransins A and B are two rare 8, 11-epoxy iridoids. • Valeransin E and ferulaldehyde showed significant anti-influenza virus activities. • Ferulaldehyde exhibited inhibitory effect on NO production.

Effect of Structural Differences in Naringenin, Prenylated Naringenin, and Their Derivatives on the Anti-Influenza Virus Activity and Cellular Uptake of Their Flavanones.

Vaccines and antiviral drugs are widely used to treat influenza infection. However, they cannot rapidly respond to drug-resistant viruses. Therefore, new anti-influenza virus strategies are required. Naringenin is a flavonoid with potential for new antiviral strategies. In this study, we evaluated the antiviral effects of naringenin derivatives and examined the relationship between their cellular uptake and antiviral effects. Madin-Darby canine kidney (MDCK) cells were infected with the A/PR/8/34 strain and exposed to the compound-containing medium for 24 h. The amount of virus in the supernatant was calculated using focus-forming reduction assay. Antiviral activity was evaluated using IC50 and CC50 values. Cells were exposed to a constant concentration of naringenin or prenylated naringenin, and intracellular uptake and distribution were evaluated using a fluorescence microscope. Prenylated naringenin showed strong anti-influenza virus effects, and the amount of intracellular uptake was revealed by the strong intracellular fluorescence. In addition, intracellular distribution differed depending on the position of the prenyl group. The steric factor of naringenin is deeply involved in influenza A virus activity, and prenyl groups are desirable. Furthermore, the prenyl group affects cellular affinity, and the uptake mechanism differs depending on its position. These results provide important information on antiviral strategies.