Antiviral Activity Research Articles

Synthetic Methodology, SAR and Pharmacology of Commercialized Preparations Employing 1, 2, 4‐Triazole Analogues

AbstractThe domain of medicinal chemistry has witnessed a notable surge of interest in triazoles owing to their unique structural characteristics and wide range of applications. The versatility of their synthesis methods has facilitated the creation of compound libraries with remarkable pharmacological activities, including antiviral, antiepileptic, anxiolytic, hypnotic/sedatives anticancer, antifungal, and antidepressant activities. Several techniques have been documented in the literature for generating 1,2,4‐triazole derivatives. The mechanisms governing the pharmacological effects of the formulations containing 1,2,4‐triazoles were elucidated and made clear. In addition to reviewing existing marketed formulations, this review explores emerging trends and innovations in this field. This review offers a comprehensive perspective on the importance of triazoles for influencing contemporary research, fostering innovation, and driving technological progress.

Targeting Diabetes with Azole-derived Medicinal Agents.

Azoles have long been regarded as an ideal scaffold for the development of numerous innovative therapeutic agents as well as other incredibly adaptable and beneficial chemicals with prospective uses in a variety of fields, including materials, energetics (explosophores), and catalysis (azole organocatalytic arbitration). Azoles exhibit promising pharmacological activities, including antimicrobial, antidiabetic, antiviral, antidepressant, antihistaminic, antitumor, antioxidant, antiallergic, antihelmintic, and antihypertensive activity. According to a database analysis of U.S. FDAapproved medications, 59% of specific medications are connected to small molecules that have heterocycles having nitrogen atoms. The azole moiety has impressive electron abundance. Azoles promptly attach to various receptors as well as enzymes in the physiological environment via distinct specialized interactions, contributing to their anti-diabetic potential. This review encompasses the recent research progress on potent azole-derived antidiabetic agents that can be used as an alternative for the management of type-2 diabetes.

Cyclodextrin-based iodophors with high iodine retention in solid state and in dilute solutions

Iodine is a broad-spectrum antiseptic with the advantage of not inducing bacterial resistance, but its use is limited by volatility. This issue can be overcome by using “iodophors”, which are molecular systems able to retain iodine and provide its sustained release. Cyclodextrins have proven effective in stabilizing iodine in solution through the formation of complexes, the preparation of which in solid form could offer additional benefits in terms of handling and storage. A series of cyclodextrins (CD) were tested for their ability to form solid complexes with iodine and it was found that the addition of potassium iodide in the solid-state preparation of the complexes significantly increases both iodine incorporation and long-term stability compared to the solids obtained without added potassium iodide. Dilute aqueous solutions of the obtained complexes were monitored for their iodine content in different conditions and excellent stability was observed in some cases. Furthermore, these cyclodextrin‑iodine complexes showed no cytotoxic effects on human corneal epithelial cells (HCE-2) while displayed very high antimicrobial (against Staphylococcus epidermis) and antiviral (against Human adenovirus 5) activities. These findings highlight the potential of cyclodextrins as a versatile platform for the development of solid iodophors as an alternative to the traditional povidone-iodide formulation.

Phyllanthus-derived Naturally-occurring Products: An Overview of their Effects against Viruses in Cell Models

Background: Infectious diseases are considered a global public health problem, with viruses being the predominant infectious agents afflicting the human population. The most used control alternatives are the search and development of vaccines and drugs. Nevertheless, their efficacy has limitations related to the immune response stimulation, resistance mechanisms, costeffort ratio, development, and production. An alternative to these drawbacks is the search for compounds isolated from plants with antiviral and/or virucidal properties. The genus Phyllanthus is a plant group producing compounds that gathers an antiviral and virucidal spectrum on different biological models. However, there is no complete review of their properties against viruses in cell models. Objective: To compile and analyse the more relevant information on the antiviral and virucidal activity in cell models, phytochemical composition, and generalities of the genus Phyllanthus. Method: The information was assembled from a general search for articles in various databanks, and the information was organized, tabulated, and discussed. Results: The taxonomic classification of the genus Phyllanthus showed discrepancies between different authors and publications. The antiviral and virucidal effects of Phyllanthus naturallyoccurring compounds on cell models showed a broad spectrum and a high chemical diversity mainly related to phenols and polyphenols. Conclusion: Antiviral and virucidal properties of Phyllanthus-derived compounds showed promising results as controlling agents against viral infections in different cell models, particularly in the viral replication and translation processes. Further studies are required to elucidate the specific mechanisms involved in these natural alternatives to expand their efficient and effective applications.

Trichosanthin elicits antitumor activity via MICU3 mediated mitochondria calcium influx

IntroductionTrichosanthin (TK) is a glycoprotein extracted from the Chinese medicinal herb Trichosanthes kirilowi, which has anti-virus and anti-tumor activity. However, the target and detailed mechanism of TK remains elusive. ObjectivesWe aimed to identify novel antitumor targets of TK in lung adenocarcinoma and study its anti-tumor mechanism. MethodsWe utilized a Lewis lung carcinoma mouse model to evaluate the inhibition of TK on tumor growth. CCK8 assay was utilized to calculate IC50 of trichosanthin on A549 and H1299. In-vitro cellular assays and in-vivo xenograft mice studies were used to investigate MICU3 overexpression and TK treatment on tumor growth. Fluo-4 dye and JC-1 staining was used to measure the mitochondrial calcium levels and membrane potential. H&E and immunohistochemistry staining were applied the asses the effect of TK on tumor and microenvironment. RNA sequencing was applied to analyze transcriptome changes in TK-treated and MICU3-overexpressed tumor cells. The influence of trichosanthin on DNMT3B expression and MICU3 methylation were detected by qPCR and Western blotting. Transcriptional activity of the MICU3 gene was measured by ChIP-PCR and luciferase assays. ResultsTrichosanthin ihibited the tumor growth in vivo, resulting cancer cell growth inhibition and cell death, with almost no effect on normal cells. IC50 of trichosanthin in A549 and H1299 cells were 62.8 μg/ml and 39.7 μg/ml, respectively. Mitochondrial Calcium Uptake Family complex MICU3 was shown to associated with favorable prognosis and was upregulated upon trichosanthin treatment, along with reduces tumor cell growth and migration, and increased cell death both in vitro and in vivo. Increased mitochondrial calcium level was observed in MICU3 overexpression cells. Pathway analysis of RNA-seq data revealed that cytokine and receptor pathways were enriched in MICU3-overexpressing cells. Trichosanthin decreased DNMT3B expression and altered MICU3 methylation while increased FOSL2 expression and reduced methylation that correlated with increased transcription of the MICU3 gene. ConclusionTrichosanthin elicits antitumor activity in lung adenocarcinoma via repressing DNMT3B and increasing FOSL2, which in turn induces MICU3-mediated mitochondrial calcium influx and tumor cell death.

Antiviral activity of isoliquiritigenin against SVCV in aquaculture: A dual approach of immune modulation and viral inhibition

Isoliquiritigenin, a flavonoid from Glycyrrhiza glabra, demonstrates potent antiviral properties by enhancing host defenses through antioxidative and immunomodulatory mechanisms. Our in vitro data demonstrate that isoliquiritigenin significantly inhibits spring viremia of carp virus (SVCV) at concentrations up to 100 μg/ml without inducing cytotoxicity, effectively reducing viral replication and the production of new viral particles. Treatment with isoliquiritigenin markedly reduced the cytopathic effects in EPC cells, improving cell viability by more than 50 %. Furthermore, isoliquiritigenin enhances resistance to SVCV infection by significantly reducing intracellular the viral load when cells are pretreated for up to 24 h. This inhibition primarily occurs during the viral replication and assembly phases, without affecting viral binding or entry. Additionally, isoliquiritigenin strengthens antioxidant defenses and modulates immune responses, thereby reducing oxidative damage and interferon production. In vivo experiments with juvenile carp corroborate the antiviral efficacy of isoliquiritigenin, showing significantly reduced mortality rates and the viral load in SVCV-infected fish. These findings highlight the potential of isoliquiritigenin as an antiviral agent in aquaculture, providing a sustainable alternative to traditional chemotherapeutics by concurrently inhibiting viral replication and enhancing host immune defenses.

Dasatinib interferes with HIV-1 proviral integration and the inflammatory potential of monocyte-derived macrophages from people with HIV

HIV-1 infection is efficiently controlled by the antiretroviral treatment (ART) but viral persistence in long-lived reservoirs formed by CD4 + T cells and macrophages impedes viral eradication and creates a chronic inflammatory environment. Dasatinib is a tyrosine kinase inhibitor clinically used against chronic myeloid leukemia (CML) that has also showed an anti-inflammatory potential. We previously reported that dasatinib is very efficient at interfering with HIV-1 infection of CD4 + T cells by preserving the antiviral activity of SAMHD1, an innate immune factor that blocks T-cell activation and proliferation and that is inactivated by phosphorylation at T592 (pSAMHD1). We observed that short-term treatment in vitro with dasatinib significantly reduced pSAMHD1 in monocyte-derived macrophages (MDMs) isolated from people with HIV (PWH) and healthy donors, interfering with HIV-1 infection. This inhibition was based on low levels of 2-LTR circles and proviral integration, while viral reverse transcription was not affected. MDMs isolated from people with CML on long-term treatment with dasatinib also showed low levels of pSAMHD1 and were resistant to HIV-1 infection. In addition, dasatinib decreased the inflammatory potential of MDMs by reducing the release of M1-related cytokines like TNFα, IL-1β, IL-6, CXCL8, and CXCL9, but preserving the antiviral activity through normal levels of IL-12 and IFNγ. Due to the production of M2-related anti-inflammatory cytokines like IL-1RA and IL-10 was also impaired, dasatinib appeared to interfere with MDMs differentiation. The use of dasatinib along with ART could be used against HIV-1 reservoir in CD4 and macrophages and to alleviate the chronic inflammation characteristic of PWH.

Phytochemical composition and therapeutic potential of Caralluma edulis a cholistani plant

This study explores C. edulis, a plant indigenous to the Cholistan desert, locally known as Pimpa or Seetu, traditionally consumed as a vegetable. Our research aimed to comprehensively analyze its phytochemical constituents, and evaluate its antibacterial, antioxidant, antiviral, anti-inflammatory, antidiabetic, and antipyretic potentials. Utilizing a range of extracts including methanol (MtOH), ethanol (EtOH), ethyl acetate (EA), n-hexane (n-hex), dichloromethane (DCM), and aqueous (Aq), for effective extraction of phytochemicals from C. edulis. Standard biochemical assays and High-Performance Liquid Chromatography-Photodiode Array (HPLC-PDA) were used for analysis of phenolic compounds. Antibacterial effect(s) were confirmed through disc diffusion method and min inhibitory concentrations (MICs). The antioxidant activity was assessed through the Ferric Reducing Antioxidant Power (FRAP) assay and the DPPH radical scavenging method. In vivo antiviral potential was assessed through Hemagglutination (HA) test. Anti-inflammatory, antidiabetic, and antipyretic activities were performed on female albino rats using carrageenan, alloxan monohydrate and yeast-induced methods, respectively. Statistical analysis was done using standard one way ANOVA.Our findings revealed a rich diversity of phenolic compounds and the presence of proteins, alkaloids, and carbohydrates in C. edulis. MtOH and n-hex extracts demonstrated deep antiviral activity against various viral strains. In vivo toxicology studies indicated no significant toxicity at doses up to 5 g/kg. The DCM extract has shown notable anti-inflammatory effects, and EA extract was leading in antipyretic activity. All extracts, except MtOH, exhibited antidiabetic properties.In conclusion, C. edulis emerges not only as a valuable nutritional source but also as a potent alternative medicinal resource, offering wide range of therapeutic benefits.

Selective and complementary antimicrobial and antiviral activity of silver, copper, and selenium nanoparticle suspensions in deep eutectic solvent

Metallic and nonmetallic nanoparticles are bioactive compounds that exhibit broad resistance to bacteria, fungi, and even viruses. In this paper, a deep eutectic solvent (DES) based on betaine, glucose, and ethylene glycol was used to obtain suspensions of silver, copper, and selenium nanoparticles. Depending on the nanoparticle precursor used, Ag, Cu, and Se nanoparticles (NPs) with an average particle size of 50−100 nm were prepared, and the properties of the products were confirmed by the STEM, XPS, DLS, and UV-VIS methods. The use of a DES, without the need for additional reactants, allowed the production of stable nanoparticles with increased bioactivity against microorganisms. The obtained systems showed high bioactivity against strains of S. aureus, E. coli, and C. albicans. Nanosuspensions, by generating reactive oxygen species (ROSs), caused enzyme inactivation and the inhibition of the metabolic processes of microorganisms. Particle-generated cell degradation processes were investigated through ROS generation assays, API assays, the determination of the MIC/MBC, and cell decomposition rate assays in the early logarithmic growth phase. Copper nanoparticles derived from copper(II) acetate were also highly active against the human influenza A/H1N1 viruses, human coronavirus (HCoV-OC43, Betacoronavirus 1), and vesicular stomatitis virus (VSV, Rhabdoviridae), showing a virus titer reduction of more than 93.7−99.96%.

Synthesis and pharmacodynamic evaluation of 2-aminoindole derivatives against influenza A virus in vitro/vivo

Influenza virus is a kind of respiratory pathogen with high morbidity and mortality, which still threatens human health. Existing anti-influenza drugs have various limitations, such as the inability to alleviate body injury and side effects. There remains an urgent need to develop a novel antiviral drug to efficiently inhibit viral infection while avoiding body injury. A series of 2-aminoindole derivatives were synthesized via the TMSOTf-catalyzed reactions of N-arylynamides with sulfilimines and evaluated for their anti-influenza virus activity. The experimental results showed that 2-aminoindole 3h had significant antiviral activity (EC50 = 8.37 ± 0.65 μM) and the lowest cytotoxicity (CC50 = 669.26 ± 11.42 μM) in vitro. 2-Aminoindole 3h could inhibit viral replication by effectively binding to RNA-dependent RNA polymerase (RdRp), and could also directly target host cells to inhibit cytokine storms and apoptosis induced by viral infection, thereby improving host cell survival rate. In addition, viral load and organ injury in the lung tissue of infected mice were effectively reduced by 2-aminoindole 3h with satisfactory biosafety. These findings highlight the potential of a valuable therapeutic option against influenza infection while also laying the foundation for further research and development in this area.

PARP7i Clinical Candidate RBN-2397 Exerts Antiviral Activity by Modulating Interferon-β Associated Innate Immune Response in Macrophages.

Polyadenosine diphosphate-ribose polymerase 7 (PARP7) acts as a suppressor of the type I interferon (IFN) signaling pathway via suppressing TANK-binding protein 1 (TBK1). Research study indicates that inhibition of PARP7 could potentially regulate tumor immunity. However, the effect of PARP7 inhibition on innate antiviral immunity in macrophages as well as the underlying mechanism have not been demonstrated else well. We report herein that PARP7 inhibitor clinical candidate RBN-2397 could augment type I interferon (IFN-I) production in macrophages by elevating retinoic acid-inducible gene I (RIG-I) and stimulator of interferon genes (STING) signaling pathways. Treatment with RBN-2397 leads to increased pattern recognition ligands-induced interferon-β production in primary bone marrow-derived macrophages (BMDM) and RAW264.7 cells. Additionally, RBN-2397 suppresses viral replication efficiency in macrophages infected by vesicular stomatitis virus (VSV) and amplifies the expression of interferon-stimulated chemokine genes (ISGs). Mechanistically, RBN-2397 promotes TBK1 phosphorylation, consequently leading to the amplified activation of RIG-I and STING signaling pathways. Furthermore, RBN-2397 enhances the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT2 induced by IFN-α/β and the expression of chemokine genes in macrophages in response to IFN stimulation. In vivo experiments demonstrated that RBN-2397 enhances innate antiviral immunity in mice infected with VSV, resulting in increased serum IFN-β levels, reduced viral loads, and alleviated pulmonary inflammatory responses of the VSV-infected mice. In conclusion, our findings highlight the potential of RBN-2397 as a promising antiviral therapeutic agent for enhancing the IFN-relative antiviral immune defense in host.

Uncovering the Potent Antiviral Activity of the Sesterterpenoids from the Sponge Ircinia Felix Against Human Adenoviruses: from the Natural Source to the Total Synthesis.

Human Adenovirus (HAdV) infections in immunocompromised patients can result in disseminated diseases with high morbidity and mortality rates due to the absence of available treatments for these infections. The sponge Ircinia felix was selected for the significant anti-HAdV activity displayed by its organic extracts. Its chemical analysis yielded three novel sesterterpene lactams, ircinialactams J-L, along with three known sesterterpene furans which structures were established by a deep spectrometric analysis. Ircinialactam J displayed significant antiviral activity against HAdV without significant cytotoxicity, showing an effectiveness 11 times greater than that of the standard treatment, cidofovir®. Comparison of the antiviral evaluation results of the isolated compounds allowed us to deduce some structure-activity relationships. Mechanistic assays suggest that ircinialactam J targets an early step of the HAdV replicative cycle before HAdV genome reaches the nucleus of the host cell. The first total synthesis of ircinialactam J was also accomplished to prove the structure and to provide access to analogues. Key steps are a regio- and stereoselective construction of the trisubstituted Z-olefin at Δ7 by iron-catalyzed carbometallation of a homopropargylic alcohol, a stereoselective methylation to generate the stereogenic center at C18, and the formation of the (Z)-Δ20 by stereoselective aldol condensation to introduce the tetronic acid unit. Ircinialactam J is a promising chemical lead to new potent antiviral drugs against HAdV infections.

Expression of Toll-like Receptor Genes and Antiviral Cytokines in Macrophage-like Cells in Response to Indole-3-carboxylic Acid Derivative

Ongoing outbreaks and often rapid spread of infections caused by coronaviruses, influenza, Nipah, Dengue, Marburg, monkeypox, and other viruses are a concern for health authorities in most countries. Therefore, the search for and study of new antiviral compounds are in great demand today. Since almost all viruses with pandemic potential have immunotoxic properties of various origins, particular attention is paid to the search and development of immunomodulatory drugs. We have synthesised a new compound related to indole-3-carboxylic acid derivatives (hereinafter referred to as the XXV) that has antiviral and interferon-inducing activity. The purpose of this work is to study the effect of the XXV on the stimulation of the expression of toll-like receptor genes, interferons, and immunoregulatory cytokines in a macrophage-like cell model. In this study, real-time PCR methods were used to obtain data on the transcriptional activity of genes in macrophage-like cells. Stimulation of the genes of toll-like receptors TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 was detected. A high-fold increase in stimulation (from 6.5 to 16,000) of the expression of the TLR3 and TLR4 genes was detected after 4 h of exposure to the XXV. Increased activity of interferon (IFNA1, IFNA2, IFNB1, IFNK, and IFNλ1) genes with simultaneous stimulation of the expression of interferon receptor (IFNAR1 and IFNAR2) genes and signalling molecule (JAK1 and ISG15) genes was detected. Increased fold stimulation of the expression of the cytokine genes IL6, TNFA, IL12A, and IL12B was also observed. Thus, it is shown that the XXV is an activator of TLR genes of innate immunity, which trigger signalling mechanisms of pathogen “recognition” and lead to stimulation of the expression of genes of proinflammatory cytokines and interferons.

The herbicidal activity and mechanism of Talaromyces purpureogenus CY-1 metabolites.

Studies have shown that Talaromyces can produce a large number of secondary metabolites in its metabolic process, many of which have good insecticidal, antibacterial, antitumor, antiviral and other biological activities. In order to explore the herbicidal activity and mechanism of Talaromyces purpureogenus CY-1, we determined the inhibitory effect of the fermentation broth of the CY-1 strain on weeds, identified the major active components, and further investigated the herbicidal mechanism. The results showed that CY-1, with IC50 values of 5.40 g/L and 4.39 g/L, respectively, exhibited good herbicidal activity against Xanthium sibiricum and Amaranthus lividus. Spraying CY-1 strain fermentation broth on redroot pigweed resulted in plant protection efficiencies and fresh weight protection efficiencies of 83.7% and 87%, respectively. The active component identified in the broth was 2-(3-hydroxybenzoyloxy) acrylic acid. Treatment of Amaranthus lividus with 2-(3-hydroxybenzoyloxy) acrylic acid resulted in trends of increasing superoxide dismutase activity, peroxidase activity, respiratory rate, cytochrome oxidase activity, and soluble protein content, followed by a decrease. Peroxidase activity, relative conductance and malondialdehyde content gradually increased, while acetyl lactate synthase and glutamine synthetase initially decreased and gradually returned to normal. The soluble sugar content showed a gradual decrease. The findings of the present study indicate that 2-(3-hydroxybenzoyloxy) acrylic acid can induce oxidative stress in plants, damaging plant cell walls, weakening respiratory activity, inhibiting protein synthesis and sugar metabolism, ultimately leading to weed wilting and death. © 2024 Society of Chemical Industry.

Button-Push On-Demand Synthesis for Rapid Optimization of Antiviral Peptidomimetics.

The optimization of hit compounds into drug candidates is a pivotal phase in drug discovery but often hampered by cumbersome manual synthesis of derivatives. While automated organic molecule synthesis has enhanced efficiency, safety, and cost-effectiveness, achieving fully automated multistep synthesis remains a formidable challenge due to issues such as solvent and reagent incompatibilities and the accumulation of side-products. We herein demonstrate an automated solid-phase flow platform for synthesizing α-keto-amides and nitrile peptidomimetics, guided by docking simulations, to identify potent broad-spectrum antiviral leads. A compact parallel synthesizer was built in-house, capable of producing 5 distinct molecules per cycle; 525 reactions could be finished within three months to generate 42 derivatives for a structure-activity relationship (SAR) investigation. Among these, ten derivatives exhibited promising target inhibitory activity (IC50 < 100 nM) including two with antiviral activity (EC50 < 250 nM). The platform, coupled with digital chemical recipe files, offers rapid access to a wide range of peptidomimetics, serving as a valuable reservoir for broad-spectrum antiviral candidates. This automated solid-phase flow synthesis approach expedites the generation of previously difficult complex molecular scaffolds. By integration of SPS-flow synthesis with medicinal chemistry campaign, >10-fold target inhibitory activity was achieved from a small set of derivatives, which indicates the potential to shift the paradigm of drug discovery.

Anti-dengue viral activity of Glycyrrhiza glabra roots in Vero cells

Despite being a global public health problem, there are no antiviral agents for dengue. Plants are the sources of most approved drugs and many phytochemicals have exhibited in vitro antiviral activity. We explored the antiviral potential of the aqueous extract of Glycyrrhiza glabra roots (GGaq) on dengue viruses. Plaque reduction antiviral assay for half maximal inhibitory concentrations (IC50) was done in Vero cells infected with dengue serotypes 1–4 and exposed to varying concentrations of GGaq. Half-maximal cytotoxic concentration (CC50) of the GGaq was 651.9 µg/mL. The IC50 of the four dengue serotypes (10–50 µg/mL) indicated moderate inhibition by GGaq. 98–100% inhibition of all dengue serotypes was seen with GGaq at the maximum nontoxic dose. Preparative thin layer chromatography of GGaq, isolated sub fractions E and F which had low to moderate antiviral activity (IC50 12.65–85.95 and IC50 13.14–69.27 respectively). They exhibited good therapeutic potential only for dengue serotype-4. Virus adsorption to cells was significantly inhibited by GG (50%) and sub fraction E (24.9%). Chloroquine diphosphate was used as the positive control in all assays. The aqueous extract of GG was non-toxic and had better antiviral activity than sub fractions E and F.

Hylotelephium telephium (L) H. Ohba leaves juice improves herpetic lesions: new findings from in vitro investigations

The efficacy of Hylotelephium telephium (L.) H. Ohba (better known with its botanical synonym Sedum telephium L.) fresh leaf juice in the treatment of Herpes labialis wounds has been reported in traditional medicine in particular in Central regions of Italy; however, scientific insights are missing and the mechanism of action is not well understood. Aim of this study was to investigate the biological properties of S. telephium that underlie its ability to heal herpetic lesions. S. telephium fresh leaf juice (STJ) was analysed to obtain phytochemical information and tested in vitro to evaluate its antiviral activity against HSV-1 in Vero cells, then, according to computational predictions, immunomodulatory properties of STJ in human lympho-monocytes (PBMC), as well as its effect on cell viability in human keratinocytes (HaCaT cells), were also evaluated. Our results, at least in part, may explain the improvement of herpetic lesions empirically observed in patients treated with STJ: such improvement was not related to direct anti-viral effect of the juice but to its experimentally confirmed activity as cell viability booster and immunomodulatory agent.

Prospects of Carica papaya in the treatment of human viral infections: A comprehensive and a systematic review

BackgroundViruses cause various human diseases, some of which become pandemic outbreaks lack effective treatments and vaccines. This study gathered data on Carica papaya's antiviral effects against various human viruses, highlighting its potential as a natural treatment. Through in-vitro, in-vivo, and clinical study analysis, we illustrated the potential of Carica papaya in combating viral infections and its potential role in cure of common viral diseases. Methodology: Research papers on antiviral activity of Carica papaya were identified by using specific keywords in PUBMED, Google Scholar, and ScienceDirect databases. Articles published between January 2015 and March 2024 were screened for inclusion. Eligible studies utilized Carica papaya leaves (powder or juice) or fruits to investigate their effects against human viral infections. Each selected study applied either qualitative or quantitative antiviral assays to assess the efficacy of Carica papaya in combating human viruses. ResultsFifteen studies went through assessment for antiviral properties of Carica papaya, 7 (46.67 %) of them displayed significant activity against the dengue virus, while 1 study (6.67 %) demonstrated moderate/less effectiveness against dengue serotype-2. Two studies (13.33 %) found no anti-dengue effects. Additionally, Carica papaya exhibited strong antiviral activity against SARS-CoV-2 in 2 studies (13.33 %). One study (6.67 %) showed inhibition of both dengue serotype-2 and chikungunya, and 1 study (6.67 %) each demonstrated inhibitory effects against human immunodeficiency virus and Zika virus infections. ConclusionThe present study listed human diseases for which Carica papaya revealed significant antiviral effects against Dengue virus, Severe acute respiratory syndrome, Human immunodeficiency virus-I, Chikungunya virus and Zika virus suggesting its potential as a treatment candidate for all these viruses. However, the majority of the research involved in-vitro screening, with minimal in-vivo and clinical testing. Further in-vivo studies and clinical trials should be conducted to explore the potential of Carica papaya in the treatment of human viral infections.

The Reaction of Fenchone and Camphor Hydrazones with 5-Acyl-4-Pyrones as a Method for the Synthesis of New Polycarbonyl Conjugates: Tautomeric Equilibrium and Antiviral Activity.

Selective synthesis of polycarbonyl conjugates of (+)-fenchone and (+)-camphor was carried out (44-91 % yields) via the ring-opening transformation of 5-acyl-4-pyrones with hydrazones of the corresponding monoterpenoids. A strong influence of the hydrazone fragment on the observed tautomeric equilibrium of the tricarbonyl system was shown. Although the major tautomer of the conjugates is the acyclic polycarbonyl form, the camphor-based conjugates undergo new type of ring-chain tautomerism, diketoenaminone-dihydropyridone equilibrium, and predominantly exist in the cyclic dihydropyridone form in DMSO-d6. The polyketones can undergo intramolecular cyclization to form N-amino-4-pyridones in high selectivity. In vitro screening for activity against the influenza virus H1 N1 and vaccinia virus was estimated for the obtained conjugates. The (+)-fenchone derivatives demonstrated the higher activity against vaccinia virus than camphor derivatives. The conjugate, which was prepared from diethyl isochelidonate and hydrazone (+)-fenchone, showed the highest activity against vaccinia virus (SI=17).

Potential novel HIV-1 reverse transcriptase inhibitors: a modeling and evaluation approach

Human immunodeficiency viru (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS), a disease that severely weakens the immune system and makes patients more susceptible to infections. Although there is no definitive cure for HIV, advances in drug development offer promising prospects. In this study, we targeted HIV-1 reverse transcriptase by performing virtual screening (VS) to identify novel candidate compounds. From a database of compounds similar to the inhibitor thymidine-5'-triphosphate (TTP), three compounds (CID441663, CID123650073, and CID123789980) were selected for their docking scores, which outperformed those of the reference compound TTP (-6.2302 kcal/mol). These compounds were then subjected to ADMET, PASS, and DFT analyses. Interestingly, all three ligands showed a broad spectrum of predicted antiviral activity, including targets related to human herpes virus and HIV. Specifically, while TTP primarily targets HIV-1 reverse transcriptase, the top three ligands were predicted to target HIV-1 integrase, with CID441663 and CID123789980 displaying higher confidence in this target compared to CID123650073. These findings suggest that the candidate ligands should undergo further in vitro validation to determine their precise roles as inhibitors or antagonists, and to confirm their selective targeting of HIV-related proteins.