Antiviral Research Articles

Exploring physicochemical characteristics of cyclodextrin through M-polynomial indices

Cyclodextrin, a potent anti-tumor medication utilized predominantly in ovarian and breast cancer treatments, encounters significant challenges such as poor solubility, potential side effects, and resistance from tumor cells. Combining cyclodextrin with biocompatible substrates offers a promising strategy to address these obstacles. Understanding the atomic structure and physicochemical properties of cyclodextrin and its derivatives is essential for enhancing drug solubility, modification, targeted delivery, and controlled release. In this study, we investigate the topological indices of cyclodextrin using algebraic polynomials, specifically the degree-based M-polynomial and neighbor degree-based M-polynomial. By computing degree-based and neighbor degree-based topological indices, we aim to elucidate the structural characteristics of cyclodextrin and provide insights into its physicochemical behavior. The computed indices serve as predictive tools for assessing the health benefits and therapeutic efficacy of cyclodextrin-based formulations. In addition, we examined that the computed indices showed a significant relationship with the physicochemical characteristics of antiviral drugs. Graphical representations of the computed results further facilitate the visualization and interpretation of cyclodextrin's molecular structure, aiding researchers in designing novel drug delivery systems with improved pharmacological properties.

Toxicity of antiviral Remdesivir on human liver’s ATP binding cassette subfamily D member 3 transporters

Background and objective: The World Health Organization advises against the use of the antiviral drug Remdesivir to treat severe COVID-19 infections due to potential toxicity. The molecular mechanism of this toxicity is not well established. ATP-binding cassette (ABC) transporters play an essential role in the transport of various drugs in many illnesses. Objective: This study examines the possible role of ATP-binding cassette, subfamily D, member 3 (ABCD3) in Remdesivir toxicity. Methods: Real-time PCR and MTT assays were used to demonstrate the toxicity of Remdesivir on ABCD3 gene expression in the HepG2 cell line. Enzyme-linked immunosorbent assay was used to detect serum ABCD3 levels, Prestige24i was used to detect C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) in the serum. Nano-Checker710 was used to detect D-dimer in the serum of the patients. Results: Remdesivir exhibits dose-dependent toxicity to the HepG2 cell line. The drug toxicity is significantly increased at three doses of 5, 10, and 20 µg/ml in virus-free hepatic cell lines. It suppressed ABCD3 gene expression in both the HepG2 cell line and COVID-19 patients’ sera. COVID-19 virus increases serum levels of CRP, ALT, AST and D-dimer. The drug lowers serum CRP, transiently lowers D-dimer, and increases ALT and AST levels. Conclusion: Remdesivir suppressed ABCD3 gene expression and increased levels of inflammatory markers. Remdesivir contributes to hepatocyte damage independently of the COVID-19 virus.

MicroRNA mediated suppression of airway lactoperoxidase by TGF-β1 and cigarette smoke promotes airway inflammation

Transforming Growth Factor Beta1 (TGF-β1) signaling is upregulated in Chronic Obstructive Pulmonary disease (COPD), smokers, and people living with HIV. Cigarette smoking and HIV are also independent risk factors for COPD. Chronic inflammation is a hallmark of COPD. However, the underlying mechanisms remain unknown. Previous research has suggested that TGF-β1 alters the airway epithelial microRNAome and transcriptome, potentially contributing to lung inflammation. The Lactoperoxidase (LPO) system is an integral component of innate immunity within the airway. LPO plays a crucial role in host defense by catalyzing the oxidation of thiocyanate to hypothiocyanite in the presence of hydrogen peroxide (H2O2), generating a potent antibacterial and antiviral agent. Additionally, the LPO system potentially aids in maintaining cellular redox balance by reducing the levels of H2O2, thus mitigating oxidative stress within the airway epithelium. LPO dysfunction can impair immune responses and exacerbate inflammatory processes in respiratory diseases.In this study, primary bronchial epithelial cells and bronchial cell lines were treated with TGF-β1 and exposed to cigarette smoke to characterize the effect of these factors on LPO and their downstream effects. RT-qPCR and Western Blot were applied to quantify mRNA and proteins’ expression. The levels of H2O2 were detected using the Amplex Red Assay. Magnetofection and transfection were applied to probe the effect of miR-449b-5p. Staining procedures using the MitoTracker Green and C12FDG dyes were used to establish mitochondria mass and senescence. The levels of pro-inflammatory cytokines were measured via Luminex assays.We found that TGF-β1 and cigarette smoke suppressed airway LPO expression, increasing H2O2 levels. This increase in H2O2 had downstream effects on mitochondrial homeostasis, epithelial cellular senescence, and the pro-inflammatory cytokine response. We demonstrate for the first time that airway LPO is regulated by TGF-β1-induced miRNA-mediated post-transcriptional silencing through miR-449b-5p in the lungs. Further, we identify and validate miR-449-5p as the candidate miRNA upregulated by TGF-β1, which is involved in LPO suppression. This paper demonstrates a new mechanism by which TGF-β1 can lead to altered redox status in the airway.

Antiviral effect of the viroporin inhibitors against Taiwan isolates of infectious bronchitis virus (IBV)

Coronaviruses (CoVs) are significant animal and human pathogens, characterized by being enveloped RNA viruses with positive-sense single-stranded RNA. The Coronaviridae family encompasses four genera, among which gammacoronaviruses pose a major threat to the poultry industry, which infectious bronchitis virus (IBV) being the most prominent of these threats. Particularly, IBV adversely affects broiler growth and egg production, causing substantial losses. The IBV strains currently circulating in Taiwan include the IBV Taiwan-I (TW-I) serotype, IBV Taiwan-II (TW-II) serotype, and vaccine strains. Therefore, ongoing efforts have focused on developing novel vaccines and discovering antiviral agents. The envelope (E) proteins of CoVs accumulate in the endoplasmic reticulum-Golgi intermediate compartment prior to virus budding. These E proteins assemble into viroporins, exhibiting ion channel activity that leads to cell membrane disruption, making them attractive targets for antiviral therapy.In this study, we investigated the E proteins of IBV H-120, as well as IBV serotypes TW-I and TW-II. E protein expression resulted in inhibited bacteria growth, increased permeability of bacteria to β-galactosidase substrates, and blocked protein synthesis of bacteria by hygromycin B (HygB). Furthermore, in the presence of E proteins, HygB also impeded protein translation in DF-1 cells and damaged their membrane integrity. Collectively, these findings confirm the viroporin activity of the E proteins from IBV H-120, IBV serotype TW-I, and IBV serotype TW-II. Next, the viroporin inhibitors, 5-(N,N-hexamethylene) amiloride (HMA) and 4,4’-diisothiocyano stilbene-2,2’-disulphonic acid (DIDS) were used to inhibit the viroporin activities of the E proteins of IBV H-120, IBV serotype TW-I, and IBV serotype TW-II. In chicken embryos and chickens infected with IBV serotypes TW-I and IBV TW-II, no survivors were observed at 6 and 11 days post-infection (dpi), respectively. However, treatments with both DIDS and HMA increased the survival rates in infected chicken embryos and chickens and mitigated histopathological lesions in the trachea and kidney. Additionally, a 3D pentameric structure of the IBV E protein was constructed via homology modeling. As expected, both inhibitors were found to bind to the lipid-facing surface within the transmembrane domain of the E protein, inhibiting ion conduction. Taken together, our findings provide comprehensive evidence supporting the use of viroporin inhibitors as promising antiviral agents against IBV Taiwan isolates.

Design, structure and antivirus molecular docking of chloridobis(1,10-phenanthroline)-(thiocyanato)-copper(II)

The reaction of sodium thiocyanate with CuCl2·2H2O salt using 1,10-phenanthtroline as a co-ligand led to chloridobis(1,10-phenanthroline)-(thiocyanato) copper(II), [Cu(Phen)2(Cl)(NCS)] (1). The structure of 1 was characterized by single crystal X-ray crystallography, UV-Visible and fluorescence spectroscopy. 1 crystallized in the monoclinic crystal system with space group P21/n and revealed a distorted octahedral coordination geometry. Electronic properties such as HOMO and LUMO energies were derived through DFT calculations. Hirshfeld surface analysis and 2D fingerprint plot was used to analyze the intermolecular interactions within the crystal structure. To develop anti-SARS-CoV-2 and anti-HIV drugs, we performed molecular docking studies for antiviral activity against the main protease (Mpro) of the SARS-CoV-2 (PDB ID: 6LU7 and 7LKD) and HIV-1 protease (PDB ID: 8FUI) viruses. The molecular docking calculations reveal that 1 with the Mpro of SARS-CoV-2 virus and HIV-1 protease virus resulted in calculated binding energies (ΔG) of −7.6, −7.5 and −7.2 kcal/mol with inhibition constant/dissociation constant (Ki/Kd ) values of 4.567, 4.432 and 4.632 µM, respectively. The in-vitro antibacterial study was conducted to check the efficacy of 1 against some selected bacteria. Further, the in-silico antiviral efficacy analysis shows the potential of this complex as an antiviral drug. 1 may be used as anti-SARS-CoV-2 and anti-HIV-1 agents.

Recent developments in the therapeutics of SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmittable respiratory virus that causes COVID-19 disease. Since its emergence in the early 2000s, SARS has posed significant public health challenges and continues to be a concern. This review provides an overview of current treatment strategies for SARS-CoV and explores the potential utility of herbal molecules in combating this viral infection. The primary treatment approach for SARS-CoV has historically centered on supportive care, which includes oxygen therapy, mechanical ventilation, and antipyretic medications to manage symptoms. However, with the ongoing advancement of medical research and our evolving understanding of the virus, several antiviral drugs have been developed and repurposed to target SARS-CoV. Recent developments in the field of herbal medicine have drawn attention to the potential efficacy of natural compounds in the management of viral infections, including SARS. Herbal molecules, characterized by their diverse bioactive constituents, exhibit antiviral properties that could be harnessed to mitigate SARS symptoms and inhibit viral replication. Ocimum sanctum, Tinospora cordifolia, Zingiber officinale, Curcuma longa, Panax ginseng, and Aloe vera have been identified for their immunomodulatory effects. This review highlights promising herbal molecules such as quercetin, and curcumin, which have demonstrated antiviral effects in–vitro and in some preclinical studies. While current treatment strategies for SARS primarily rely on supportive care and antiviral medications, the exploration of herbal molecules presents an exciting avenue for potential adjunctive therapies. Further research is required to validate their efficacy, safety profiles, and mechanisms of action. A holistic approach that combines conventional medicine with herbal remedies may offer new insights into the treatment of SARS and other viral respiratory illnesses.

Harnessing Natural Resources for Advancements in Dengue Virus Treatment.

Dengue fever, caused by the Dengue virus (DENV) and transmitted by Aedes aegypti mosquitoes, has become endemic in over 100 countries. Despite considerable research, there is a lack of specific drugs for clinical use against dengue. Hence, further exploration to identify anti-- dengue compounds is essential. In recent years, natural products have gained attention for their antiviral properties. Plant-based medicines are particularly appealing due to their safety and low toxicity. This review summarizes natural compounds with potential antiviral activity against DENV, highlighting their mechanisms of action. Various compounds, from traditional herbal remedies to novel plant isolates, show promise against dengue, targeting crucial viral proteins like the envelope protein, proteases, and RNA polymerase. Exploring natural sources of antiviral agents against dengue is crucial. These compounds offer hope for effective treatments and mitigating dengue's global impact.

Emerging Synthetic Drug Approaches for COVID-19 Treatment: An Extensive Review of Recent Findings

Background: The ongoing global pandemic of COVID-19 has underscored the urgent need for effective treatment strategies to mitigate its impact on public health. Amidst this crisis, researchers have turned to synthetic drug approaches as potential therapeutic interventions. This review aims to comprehensively analyze the recent developments in synthetic drug treatments for COVID-19, exploring their mechanisms of action, efficacy, and challenges. Objective: This review seeks to consolidate and evaluate the emerging synthetic drug approaches for COVID-19 treatment that have been investigated in recent studies. The objective is to present an upto- date overview of the landscape of synthetic drug interventions and their potential implications in combating COVID-19. Methods: A systematic literature search was conducted across databases including PubMed, Scopus, and Web of Science, utilizing keywords related to COVID-19 treatment and synthetic drugs. Studies published from May 2020 to July 2023 were included, focusing on experimental and clinical investigations of synthetic compounds with potential antiviral activity against SARS-CoV-2. Results: The review highlights a range of synthetic drug approaches that have shown promise in COVID-19 treatment. Notably, certain antiviral agents and repurposed drugs have demonstrated inhibitory effects against viral replication and reduced disease severity. Additionally, the review underscores the significance of computational approaches in identifying potential drug candidates and optimizing their interactions with viral proteins. While several synthetic drug candidates are under investigation, challenges such as drug resistance, safety concerns, and global accessibility remain critical considerations. Conclusion: This extensive review sheds light on the emerging synthetic drug approaches that hold potential for COVID-19 treatment. As the scientific community collaboratively addresses the challenges posed by this pandemic, the insights gleaned from these recent findings contribute to the ongoing efforts to identify effective therapeutic strategies against COVID-19.

Anti-enterovirus 71 activity of native fucosylated chondroitin sulfates and their derivatives

Enterovirus 71 (EV71) is recognized as a major causative agent of hand, foot, and mouth disease (HFMD), posing a significant global public health concern due to its widespread impact and resulting in a major public health issue worldwide. Despite its prevalence, current clinical therapy lacks effective antiviral agents. Fucosylated chondroitin sulfates (FCS) derived from sea cucumber exhibits a range of biological activities including potent antiviral effects. This study provides compelling evidence of the potent antiviral efficacy of FCS against EV71. To further elucidate the impact of structural variations on the anti-EV71 activity, native FCSs with diverse sulfation patterns and a varity of FCS derivatives were prepared and analyzed. Notably, this study presents the detailed structural characterization of FCSs from the sea cucumbers Holothuria scabra Jaege and Holothuria fuscopunctata. Analysis of the structure-activity relationships revealed that molecular weight, sulfated fucose branches, and sulfation pattern were all crucial factors contributing to the potent inhibitory effects of FCS against EV71. Interestingly, molecular weight emerged as the most significant structural determinant of the antiviral potency. These findings suggest the promising potential of utilizing FCS as an innovative EV71 entry inhibitor for the treatment of HFMD.

Antivirals for treatment of severe influenza: a systematic review and network meta-analysis of randomised controlled trials

The optimal antiviral drug for treatment of severe influenza remains unclear. To support updated WHO influenza clinical guidelines, this systematic review and network meta-analysis evaluated antivirals for treatment of patients with severe influenza. We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023, that enrolled hospitalised patients with suspected or laboratory-confirmed influenza and compared direct-acting influenza antivirals against placebo, standard care, or another antiviral. Pairs of coauthors independently extracted data on study characteristics, patient characteristics, antiviral characteristics, and outcomes, with discrepancies resolved by discussion or by a third coauthor. Key outcomes of interest were time to alleviation of symptoms, duration of hospitalisation, admission to intensive care unit, progression to invasive mechanical ventilation, duration of mechanical ventilation, mortality, hospital discharge destination, emergence of antiviral resistance, adverse events, adverse events related to treatments, and serious adverse events. We conducted frequentist network meta-analyses to summarise the evidence and evaluated the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. This study is registered with PROSPERO, CRD42023456650. Of 11 878 records identified by our search, eight trials with 1424 participants (mean age 36-60 years for trials that reported mean or median age; 43-78% male patients) were included in this systematic review, of which six were included in the network meta-analysis. The effects of oseltamivir, peramivir, or zanamivir on mortality compared with placebo or standard care without placebo for seasonal and zoonotic influenza were of very low certainty. Compared with placebo or standard care, we found low certainty evidence that duration of hospitalisation for seasonal influenza was reduced with oseltamivir (mean difference -1·63 days, 95% CI -2·81 to -0·45) and peramivir (-1·73 days, -3·33 to -0·13). Compared with standard care, there was little or no difference in time to alleviation of symptoms with oseltamivir (0·34 days, -0·86 to 1·54; low certainty evidence) or peramivir (-0·05 days, -0·69 to 0·59; low certainty evidence). There were no differences in adverse events or serious adverse events with oseltamivir, peramivir, and zanamivir (very low certainty evidence). Uncertainty remains about the effects of antivirals on other outcomes for patients with severe influenza. Due to the small number of eligible trials, we could not test for publication bias. In hospitalised patients with severe influenza, oseltamivir and peramivir might reduce duration of hospitalisation compared with standard care or placebo, although the certainty of evidence is low. The effects of all antivirals on mortality and other important patient outcomes are very uncertain due to scarce data from randomised controlled trials. World Health Organization.

Monkeypox: A Global Challenge - An Overview

Monkeypox is a zoonosis caused by an orthopoxvirus named monkeypox virus MPX, structurally related to smallpox virus, enveloped, brick shaped, replicates in cytoplasm. Currently spreading throughout Africa & different parts of world. Has two distinct clades, West African and Central African (Congo Basin) clades. It manifests as rashes, concentrated on face & extremities like palms & soles. Both humoral and cell mediated immunity are seen in host, diagnosed by polymerase chain reaction PCR and various serological tests. Patients receive supportive treatments along with antiviral drugs. Presently FDA approved new Mpox vaccines. Scientific community needs to extend their research work to enhance knowledge in this field. This review briefs about monkeypox in human life in context of ongoing outbreaks around the world.

High throughput screening for SARS-CoV-2 helicase inhibitors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for nearly 7 million deaths worldwide since its outbreak in late 2019. Even with the rapid development and production of vaccines and intensive research, there is still a huge need for specific anti-viral drugs that address the rapidly arising new variants. To address this concern, the National Institute of Allergy and Infectious Diseases (NIAID) established nine Antiviral Drug Discovery (AViDD) Centers, tasked with exploring approaches to target pathogens with pandemic potential, including SARS-CoV-2. In this study, we sought inhibitors of SARS-CoV2 non-structural protein 13 (nsP13) as potential antivirals, first developing a HTS-compatible assay to measure SARS-CoV2 nsP13 helicase activity. Here we present our effort in implementing the assay in a 1,536 well-plate format and in identifying nsP13 inhibitor hit compounds from a ∼650,000 compound library. The primary screen was robust (average Z’ = 0.86 ± 0.05) and resulted in 7,009 primary hits. 1,763 of these compounds upon repeated retests were further confirmed, showing consistent inhibition. Following in-silico analysis, an additional orthogonal assay and titration assays, we identified 674 compounds with IC50 <10 μM. We confirmed activity of independent compound batches from de novo powders while also incorporating multiple counterscreen assays. Our study highlights the potential of this assay for use on HTS platforms to discover novel compounds inhibiting SARS-CoV2 nsP13, which merit further development as an effective SARS-CoV2 antiviral.

Specific adsorption of antiviral drugs on ionic liquid-modified metal–organic framework: Adsorption behavior, mechanism, and DFT analysis

As emerging contaminants, antiviral drugs (ATVs) in water pose an increasing threat to human health and the ecosystem. Using specific and selective adsorption methods to remove ATVs remains challenging due to their trace concentration in real matrices. In this study, pyridine ionic liquid ([BPy][Sal])-modified metal–organic framework (MOF), a type of novel material, was synthesized as [BPy][Sal]@MOF to adsorb ATVs with different molecular structures, i.e., Arbidol (Arb) and Favipiravir (Fav). Arb adsorption followed the pseudo-second-order model, indicating that chemisorption is the dominant process. The Langmuir isothermal model showed that the maximum adsorption capacities toward Arb and Fav were 506.9 and 35.3 mg g−1, respectively, suggesting specific adsorption of Arb on [BPy][Sal]@MOF. Density functional theory (DFT) was used to investigate the specific adsorption mechanism. The molecular electrostatic potential and the intermolecular weak interaction analysis using the DFT method illustrated that the amino hydrogens in MOF could form hydrogen bonds (NHO) with the hydroxyl oxygens in Arb. Simultaneously, the indole ring in Arb could cause π–π interaction with the pyridine ring in [BPy][Sal] part from [BPy][Sal]@MOF. In contrast, the adsorption of Fav only involved π–π interaction between the benzene rings in Fav and the MOF part from [BPy][Sal]@MOF. The adsorption energy and energy gap calculation results verified that the adsorption strength of Arb was higher than that of Fav, and the key role of [BPy][Sal] in [BPy][Sal]@MOF helped achieve specific adsorption was confirmed. [BPy][Sal]@MOF exhibited exceptional recyclability after five adsorption–desorption cycles in environmental waters, demonstrating its excellent adsorption performance in practical applications.

Insight into simultaneously sludge dewatering and antiviral drugs removal by integrated particle electrodes assisted electrochemical oxidation

Given the widespread occurrence of pandemic influenza, antiviral drugs (ATVs) as emerging pollutants which are ubiquitously present in wastewater and become concentrated in sewage sludge (SS). Therefore, achieving the simultaneous elimination of ATVs during sludge dewatering holds significant importance. Herein, six representative ATVs including amantadine, rimantadine, memantine hydrochloride, imiquimod, oseltamivir, and morpholidine were detected in sewage sludge. Their partitioning between solid and liquid phases was also examined under simultaneous sludge conditioning by particle electrodes-assisted electrochemical process (3D-SAC). The findings indicated that 3D-SAC significantly enhanced sludge dewaterability, achieving a moisture content reduction to 64.22 %. The total removal rates of the six ATVs ranged from 17.97 % to 66.22 %, closely associated with the degree of sludge cells cracking. Sludge lysis resulted in the destruction of protein-like EPS structures, exposing hydrophobic bonding sites, finally releasing more bonded water and ATVs into filtrate. The ·OH induced hydroxylation, backbone cleavage, and ring-opening of ATVs occurred concurrently as the sludge flocs disrupted and structural transformed. Environmental risk assessment revealed that the ecological risks and potential toxicity associated with the sludge filtrate were significantly diminished following electrochemical conditioning (EC). This process achieved the dual objectives of contaminant degradation and enhanced sludge dewatering.

Recompensation of Chronic Hepatitis C-related decompensated cirrhosis following direct-acting antiviral therapy: Prospective Cohort study from an HCV elimination program.

Background and AimsChronic hepatitis C(CHC) related decompensated cirrhosis is associated with lower SVR-12 rates and variable regression of disease severity following direct-acting antiviral agents (DAAs). We assessed rates of SVR-12, recompensation (Baveno VII criteria), and survival in such patients. MethodsBetween July 2018-July 2023, patients with decompensated CHC-related cirrhosis post DAAs treatment, were evaluated for SVR-12 and then had 6-monthly follow-up. ResultsOf 6516 patients with cirrhosis, 1152 with decompensated cirrhosis (age 53.2±11.5 years,63% men, MELD-Na:16.5± 4.6,87% genotype 3) were enrolled. SVR-12 was 81.8% after one course; ultimately SVR was 90.8% following additional treatment. Decompensation events included ascites (1098,95.3%), hepatic encephalopathy (191,16.6%), and variceal bleeding (284,24.7%). Ascites resolved in 86% (diuretic withdrawal achieved in 24% patients). Recompensation occurred in 284(24.7%) at a median time of 16.5(IQR-14.5-20.5) months. On multivariable Cox proportional hazards analysis, low bilirubin(aHR-0.6,95%CI-0.5-0.8,P<0.001), INR(aHR-0.2,95%CI:0.1-0.3,P<0.001), absence of large esophageal varices(aHR-0.4,95%CI:0.2-0.9,P=0.048), or gastric varices (aHR-0.5,95%CI:0.3-0.7,P=0.022) predicted recompensation. Portal hypertension (PHT) progressed in 158(13.7%) patients, with rebleed in 4%. Prior decompensation with variceal bleeding (aHR-1.6,95%CI:1.2-2.8, P=0.042), and presence of large varices (aHR-2.9,95%CI:1.3-6.5,P<0.001) were associated with PHT progression. Further decompensation was seen in 221(19%);145 patients died and 6 underwent liver transplant. A decrease in MELDNa of ≥3 was in 409(35.5%) and a final MELDNa score of <10 was in 335(29%), but 2.9% developed HCC despite SVR-12. ConclusionsSVR-12 in HCV-related decompensated cirrhosis in a predominant genotype 3 population, led to recompensation in 24.7% of patients over a follow-up of 4 years in a public health setting. Despite SVR-12, new hepatic decompensation evolved in 19% and HCC developed in 2.9% of patients.

Import of extracellular 2′-3′cGAMP by the folate transporter, SLC19A1, establishes an antiviral response that limits herpes simplex virus-1

Recently it was discovered that extracellular 2′-3′cGAMP can activate the STING pathway in a cGAS-independent fashion by being transported across the cell membrane via the folate transporter, SLC19A1, the first identified extracellular antiporter of this critical signaling molecule in cancer cells. We hypothesized that this non-canonical activation of STING pathway would function to establish an antiviral state similar to that seen with the paracrine antiviral activities of interferon. Herein, we report that treatment of the monocytic cell line, THP-1 cells and SH-SY5Y neuronal cell line with exogenous 2′-3′cGAMP induces interferon production and establishes an antiviral state that limits herpes simplex virus-1 (HSV-1), a ubiquitous virus with high seropositivity in the human population. Using either pharmaceutical inhibition or genetic knockout of SLC19A1 blocks the 2′-3′cGAMP-induced inhibition of viral replication. Our data indicate SLC19A1 functions as a newly identified antiviral mediator for extracellular 2′-3′cGAMP. This work presents novel and important findings about an antiviral mechanism which information could aid in the development of better antiviral drugs in the future.

Aloperine Inhibits ASFV via Regulating PRLR/JAK2 Signaling Pathway In Vitro.

African swine fever (ASF) has become a global pandemic due to inadequate prevention and control measures, posing a significant threat to the swine industry. Despite the approval of a single vaccine in Vietnam, no antiviral drugs against the ASF virus (ASFV) are currently available. Aloperine (ALO), a quinolizidine alkaloid extracted from the seeds and leaves of bitter beans, exhibits various biological functions, including anti-inflammatory, anti-cancer, and antiviral activities. In this study, we found that ALO could inhibit ASFV replication in MA-104, PK-15, 3D4/21, and WSL cells in a dose-dependent manner without cytotoxicity at 100 μM. Furthermore, it was verified that ALO acted on the co- and post-infection stages of ASFV by time-of-addition assay, and inhibited viral internalization rather than directly inactivating the virus. Notably, RT-qPCR analysis indicated that ALO did not exert anti-inflammatory activity during ASFV infection. Additionally, gene ontology (GO) and KEGG pathway enrichment analyses of transcriptomic data revealed that ALO could inhibit ASFV replication via the PRLR/JAK2 signaling pathway. Together, these findings suggest that ALO effectively inhibits ASFV replication in vitro and provides a potential new target for developing anti-ASFV drugs.

Update on Hepatitis C Vaccine: Results and Challenges.

Therapy against the Hepatitis C virus (HCV) has significantly improved with the introduction of direct-acting antiviral drugs (DAAs), achieving over 95% sustained virological response (SVR). Despite this, the development of an effective anti-HCV vaccine remains a critical challenge due to the low number of patients treated with DAAs and the occurrence of HCV reinfections in high-risk groups. Current vaccine strategies aim to stimulate either B-cell or T-cell responses. Vaccines based on E1 and E2 proteins can elicit broad cross-neutralizing antibodies against all major HCV genotypes, though with varying efficiencies and without full protection against infection. In humans, the neutralizing antibodies induced by such vaccines mainly target the AR3 region, but their levels are generally insufficient for broad neutralization. Various HCV proteins expressed through different viral vectors have been utilized to elicit T cell immune responses, showing sustained expansion of HCV-specific effector memory T cells and improved proliferation and polyfunctionality of memory T cells over time. However, despite these advancements, the frequency and effectiveness of T-cell responses remain limited.

Repurposed Drugs during the Outbreak of Pandemic COVID-19: A Mini-Review on Their Molecular Structures and Hit-and-Trial Results.

One of the most significant threats to global public health in the 21st century is the novel coronavirus disease (COVID-19) caused by SARS-CoV-2. It rapidly turned into a global pandemic after it was identified in late 2019, and the World Health Organization announced the end of the pandemic on May 5, 2023. Current strategies for managing this disease include vaccination and repurposing antimalarial and antibiotic medications to alleviate symptoms like fever and throat pain, which are associated with acute respiratory distress syndrome (ARDS). Antiviral drugs such as chloroquine, hydroxychloroquine, azithromycin, remdesivir, and favipiravir have been repurposed for the treatment of COVID-19. They were previously recommended for treating SARS-CoV and MERS-CoV. However, the inefficacy and adverse side effects of these repurposed drugs led to a decrease in their widespread use in treating COVID-19 patients. The lack of approved drugs for combating this coronavirus and its unpredictable variants remains a significant challenge.

Evaluation of the antiviral activity of oleanolic acid against nervous necrosis virus

Viral nervous necrosis (VNN) presents a significant challenge to aquaculture due to its potential for causing mass fish mortality and resulting in substantial economic losses. Therefore, the urgent need to find antiviral drugs is paramount. This study found that oleanolic acid (OA) exhibited anti-nervous necrosis virus (NNV) activity both in vivo and in vitro. The RT-qPCR results demonstrated that OA at 10.95 μM had an inhibition rate of 99.97 %. The prevention experiments also showed that OA pretreatment effectively inhibited the replication of NNV. Furthermore, the results of indirect immunofluorescence and flow cytometry suggest that OA's anti-NNV effect may be due to its ability to inhibit NNV-induced apoptosis. The in vivo study revealed a 30 % survival rate in the OA treatment group, compared to only 10 % in the control group. Additionally, RT-qPCR results demonstrated that OA treatment upregulated immune gene expression in grouper and effectively suppressed NNV replication in the host. This study demonstrates the potential of OA as an antiviral therapeutic agent for NNV. It exerts its antiviral effect by upregulating immune gene expression. These findings provide valuable insights into the development of novel antiviral treatment strategies.