Antiviral Research Articles

Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors.

Although vaccination remains the prevalent prophylactic means for controlling Influenza A virus (IAV) infections, novel structural antivirus small-molecule drugs with new mechanisms of action for treating IAV are highly desirable. Herein, we describe a modular biomimetic strategy to expeditiously achieve a new class of macrocycles featuring oxime, which might target the hemagglutinin (HA)-mediated IAV entry into the host cells. SAR analysis revealed that the size and linker of the macrocycles play an important role in improving potency. Particularly, as a 14-membered macrocyclic oxime, 37 exhibited potent inhibitory activity against IAV H1N1 with an EC50 value of 23 nM and low cytotoxicity, which alleviated cytopathic effects and protected cell survival obviously after H1N1 infection. Furthermore, 37 showed significant synergistic activity with neuraminidase inhibitor oseltamivir in vitro.

Polyethylene Glycol-Modified Cationic Liposome as a Promising Nano Spray for Acute Pneumonia Treatment.

Acute pneumonia (AP), triggered primarily by pathogens like bacteria and viruses, is a leading cause of human mortality. Ribavirin, a broad-spectrum antiviral agent, plays a pivotal role in the treatment of AP. However, its therapeutic use is hindered by the need for high dosages and the associated cardiac and hepatic toxicities. In this study, we synthesized polyethylene glycol-modified cationic liposomes to encapsulate ribavirin (RBV-PCL) and formulated it into a spray, aiming to enhance the effectiveness of RBV through respiratory administration. Lipopolysaccharide (LPS), a compound known to induce AP models in animals, was utilized in our research. Successfully, we established an acute pneumonia model in mice using aerosol inhalation. Through animal experiments, we investigated the therapeutic effects of RBV-PCL on mice with AP. In vivo studies revealed promising results. RBV-PCL effectively prolonged the survival of mice with AP, significantly reduced the levels of inflammatory markers such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and inhibited the infiltration of neutrophils in the lungs and spleens of mice. These findings suggest that RBV-PCL can effectively suppress the inflammatory response in mice with AP, thus holding significant potential as a novel therapeutic approach for the treatment of acute pneumonia.

Hepatocellular carcinoma surveillance after HBsAg seroclearance

Hepatitis B surface antigen (HBsAg) seroclearance is considered the functional cure and the optimal treatment endpoint for chronic hepatitis B (CHB). Patients with CHB who cleared HBsAg generally have a favorable clinical course with minimal risk of developing hepatocellular carcinoma (HCC) or cirrhotic complications. Nevertheless, a minority of patients still develop HCC despite HBsAg seroclearance. While patients with liver cirrhosis are still recommended for HCC surveillance, whether other non-cirrhotic patients who achieved HBsAg seroclearance should remain on HCC surveillance remains unclear. This review provides an overview of the incidence of HBsAg seroclearance, the factors associated with the occurrence of HBsAg seroclearance, the durability of HBsAg seroclearance, the risk of developing HCC after HBsAg seroclearance, the risk factors associated with HCC development after HBsAg seroclearance, the role of HCC risk scores, and the implications on HCC surveillance. Existing HCC risk scores have a reasonably good performance in patients after HBsAg seroclearance. In the era of artificial intelligence, future HCC risk prediction models based on artificial intelligence and longitudinal clinical data may further improve the prediction accuracy to establish a foundation of a risk score-based HCC surveillance strategy. As different novel hepatitis B virus (HBV) antiviral agents aiming at HBsAg seroclearance are under active development, new knowledge is anticipated on the natural history and HCC risk prediction of patients treated with new HBV drugs.

Fabrication of biocompatible water-soluble supramolecular nanofibers of oseltamivir with methyl-β-cyclodextrin for enhanced drug release

In recent times, there has been a growing interest in the advancement of nanofiber technology using materials based on cyclodextrin (CD). This heightened interest is primarily driven by their potential applications in controlled drug release. This research aims to create the nanofibers (NF) which involves incorporating an antiviral agent, oseltamivir (OTV) into the CD cavity, forming inclusion complexes (IC) that greatly improve drug encapsulation efficiency. To assess the physicochemical properties and drug-loading capabilities of these CD-based NF, a variety of characterization techniques can be utilized. It is noteworthy that NF containing OTV:MCD-IC/PVA demonstrates a continuous release of OTV (89.25%) at acidic conditions (pH 5.8) when compared to NF holding no MCD materials. Moreover, dissolution studies reveal that the resulting material is non-toxic and readily soluble in water (less than 2 min). MTT assay indicated that the examined NF are completely safe and do not have/make any adverse effects on the cells (cell viability is more than 98%). The fibroblast cells grown on nanomatrixes composed of both OTV/PVA and OTV:MCD IC/PVA NF did not display any indications of apoptosis or nuclear shrinkage. The development of such systems holds significant promise for advancing therapeutic strategies in the management of viral infections.

N-Heterocycles as Promising Antiviral Agents: A Comprehensive Overview

Viruses are a real threat to every organism at any stage of life leading to extensive infections and casualties. N-heterocycles can affect the viral life cycle at many points, including viral entrance into host cells, viral genome replication, and the production of novel viral species. Certain N-heterocycles can also stimulate the host’s immune system, producing antiviral cytokines and chemokines that can stop the reproduction of viruses. This review focused on recent five- or six-membered synthetic N-heterocyclic molecules showing antiviral activity through SAR analyses. The review will assist in identifying robust scaffolds that might be utilized to create effective antiviral drugs with either no or few side effects.

Broadly Reactive Nanobody Targeting the H3 Hemagglutinin of the Influenza A Virus.

Monoclonal antibodies and recombinant antibody fragments are a very promising therapeutic tool to combat infectious diseases. Due to their unique paratope structure, nanobodies (VHHs) hold several advantages over conventional monoclonal antibodies, especially in relation to viral infections. Influenza A viruses (IAVs) remain a major threat to public health. The hemagglutinin (HA) protein is the main protective and immunodominant antigen of IAVs. In this study, three broadly reactive nanobodies (D9.2, E12.2, and D4.2) to H3N2 influenza strains were isolated and Fc-fusion proteins (VHH-Fcs) were obtained and characterized in vitro. This modification improved the nanobodies' binding activity and allowed for their interaction with a wider range of strains. The D9.2-Fc antibody showed a 100% protection rate against mortality in vivo in a mouse lethal model. Furthermore, we demonstrated that the observed protection has to do with Fc-FcγR interactions. These results indicate that D9.2-Fc can serve as an effective antiviral agent against the H3N2 influenza infection.

Pseudovirus-Based Systems for Screening Natural Antiviral Agents: A Comprehensive Review.

Since the outbreak of COVID-19, researchers have been working tirelessly to discover effective ways to combat coronavirus infection. The use of computational drug repurposing methods and molecular docking has been instrumental in identifying compounds that have the potential to disrupt the binding between the spike glycoprotein of SARS-CoV-2 and human ACE2 (hACE2). Moreover, the pseudovirus approach has emerged as a robust technique for investigating the mechanism of virus attachment to cellular receptors and for screening targeted small molecule drugs. Pseudoviruses are viral particles containing envelope proteins, which mediate the virus's entry with the same efficiency as that of live viruses but lacking pathogenic genes. Therefore, they represent a safe alternative to screen potential drugs inhibiting viral entry, especially for highly pathogenic enveloped viruses. In this review, we have compiled a list of antiviral plant extracts and natural products that have been extensively studied against enveloped emerging and re-emerging viruses by pseudovirus technology. The review is organized into three parts: (1) construction of pseudoviruses based on different packaging systems and applications; (2) knowledge of emerging and re-emerging viruses; (3) natural products active against pseudovirus-mediated entry. One of the most crucial stages in the life cycle of a virus is its penetration into host cells. Therefore, the discovery of viral entry inhibitors represents a promising therapeutic option in fighting against emerging viruses.

Development of Peptide Displacement Assays to Screen for Antagonists of DDB1 Interactions.

The DNA damage binding protein 1 (DDB1) is an essential component of protein complexes involved in DNA damage repair and the ubiquitin-proteasome system (UPS) for protein degradation. As an adaptor protein specific to Cullin-RING E3 ligases, DDB1 binds different receptors that poise protein substrates for ubiquitination and subsequent degradation by the 26S proteasome. Examples of DDB1-binding protein receptors are Cereblon (CRBN) and the WD-repeat containing DDB1- and CUL4-associated factors (DCAFs). Cognate substrates of CRBN and DCAFs are involved in cancer-related cellular processes or are mimicked by viruses to reprogram E3 ligases for the ubiquitination of antiviral host factors. Thus, disrupting interactions of DDB1 with receptor proteins might be an effective strategy for anticancer and antiviral drug discovery. Here, we developed fluorescence polarization (FP)-based peptide displacement assays that utilize full-length DDB1 and fluorescein isothiocyanate (FITC)-labeled peptide probes derived from the specific binding motifs of DDB1 interactors. A general FP-based assay condition applicable to diverse peptide probes was determined and optimized. Mutagenesis and biophysical analyses were then employed to identify the most suitable peptide probe. The FITC-DCAF15 L49A peptide binds DDB1 with a dissociation constant of 68 nM and can be displaced competitively by unlabeled peptides at sub-μM to low nM concentrations. These peptide displacement assays can be used to screen small molecule libraries to identify novel modulators that could specifically antagonize DDB1 interactions toward development of antiviral and cancer therapeutics.

Predicting drug-Protein interaction with deep learning framework for molecular graphs and sequences: Potential candidates against SAR-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 disease, which represents a new life-threatening disaster. Regarding viral infection, many therapeutics have been investigated to alleviate the epidemiology such as vaccines and receptor decoys. However, the continuous mutating coronavirus, especially the variants of Delta and Omicron, are tended to invalidate the therapeutic biological product. Thus, it is necessary to develop molecular entities as broad-spectrum antiviral drugs. Coronavirus replication is controlled by the viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme, which is required for the virus's life cycle. In the cases of severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV), 3CLpro has been shown to be a promising therapeutic development target. Here we proposed an attention-based deep learning framework for molecular graphs and sequences, training from the BindingDB 3CLpro dataset (114,555 compounds). After construction of such model, we conducted large-scale screening the in vivo/vitro dataset (276,003 compounds) from Zinc Database and visualize the candidate compounds with attention score. geometric-based affinity prediction was employed for validation. Finally, we established a 3CLpro-specific deep learning framework, namely GraphDPI-3CL (AUROC: 0.958) achieved superior performance beyond the existing state of the art model and discovered 10 molecules with a high binding affinity of 3CLpro and superior binding mode.

Extrahepatic Malignancies and Antiviral Drugs for Chronic Hepatitis B: A Nationwide Cohort Study.

Chronic hepatitis B (CHB) is related to an increased risk of extrahepatic malignancy (EHM), and antiviral treatment is associated with an incidence of EHM comparable to controls. We compared the risks of EHM and intrahepatic malignancy (IHM) between entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment. Using data from the National Health Insurance Service of Korea, this nationwide cohort study included treatment-naïve CHB patients who initiated ETV (n=24,287) or TDF (n=29,199) therapy between 2012 and 2014. The primary outcome was the development of any primary EHM. Secondary outcomes included overall IHM development. E-value was calculated to assess the robustness of results to unmeasured confounders. The median follow-up duration was 5.9 years, and all baseline characteristics were well balanced after propensity score matching. EHM incidence rate differed significantly between within versus beyond 3 years in both groups (P<0.1, Davies test). During the first 3 years, EHM risk was comparable in the propensity score-matched cohort (5.88 versus 5.84/1,000 person-years; subdistribution hazard ratio [SHR]=1.01, 95% confidence interval [CI]=0.88-1.17, P=0.84). After year 3, however, TDF was associated with a significantly lower EHM incidence compared to ETV (4.92 versus 6.91/1,000 person-years; SHR=0.70, 95% CI=0.60-0.81, P<0.01; E-value for SHR=2.21). Regarding IHM, the superiority of TDF over ETV was maintained both within (17.58 versus 20.19/1,000 person-years; SHR=0.88, 95% CI=0.81-0.95, P<0.01) and after year 3 (11.45 versus 16.20/1,000 person-years; SHR=0.68, 95% CI=0.62-0.75, P<0.01; E-value for SHR=2.30). TDF was associated with approximately 30% lower risks of both EHM and IHM than ETV in CHB patients after 3 years of antiviral therapy.

Study of humoral and cellular immunity following the immunization of C57Bl/6 mice with a prototype of the inactivated Chikungunya vaccine

Introduction. Chikungunya virus infection is a problem for the health care system of affected regions due to the lack of specific prevention, as well as effective antiviral drugs. The critical role of cellular immunity in viral control and clearance for the Chikungunya fever has been demonstrated in many studies. Therefore, effective stimulation of not only humoral but also cellular immunity is of undeniable importance when assessing the effectiveness of a potential vaccine for the prevention of this infection. The aim of the present study was to investigate the formation of protective immunity after administration of a drug containing inactivated Chikungunya virus (CHIKV) to C57Bl/6 mice. Materials and methods. Inactivated CHIKV (concentrations of 10 μg and 40 μg) was administered intramuscularly to C57Bl/6 mice twice with an interval of 14 days. Indicators of humoral immunity were assessed by ELISA and neutralization test (NT), cellular immunity — by the production of IFN-γ and splenocyte proliferation in vitro. The concentration of cytokines IL-1, IL-2, IL-6, IL-10, IL-12p70 and TNF was determined by ELISA. When assessing the protective immunity in animals, CHIKV was injected into the dorsal surface of the foot of the right hind paw at a dose of 2.89 ± 0.10 lg TCD50 in a volume of 20 μl. Results. The most pronounced immune response was noted to the administration of 40 μg of inactivated CHIKV, which was manifested in the balanced production of the studied cytokines, the formation of specific humoral (according to the results of ELISA and NT) and cellular — specific proliferation of splenocytes in vitro and production of IFN-γ. When assessing efficacy, the development of foot edema in immunized animals was significantly lower than in animals in the control group. Discussion. CHIKV, inactivated by beta-propiolactone, had pronounced immunogenic properties. The balance of production of pro- and anti-inflammatory cytokines, as well as the Th1/Th2 immune response, characterized the formation of adaptive immunity in mice without a pronounced inflammatory response. The formation of a specific humoral and cellular immune response has been demonstrated. A study of protection in a non-lethal animal model confirmed the efficacy of the inactivated vaccine. Conclusion. Double administration of the inactivated CHIKV vaccine at a dose of 40 μg to C57Bl/6 mice demonstrated pronounced immunogenicity, which allows us to evaluate it as a promising prophylactic vaccine.

SP2509, a specific antagonist of LSD1, exhibits antiviral properties against Porcine epidemic diarrhea virus

BackgroundPorcine epidemic diarrhea virus (PEDV), a type of coronavirus, is one of the main pathogens that can infect pigs of all ages. It causes diarrhea and acute death of newborn piglets, resulting in massive economic losses to the worldwide swine industry. While vaccination remains the primary approach in combating PEDV, it often fails to address all the challenges posed by the infection, particularly in light of the emergence of evolving mutant strains. Therefore, there is a critical need to identify potent antiviral drugs that can effectively safeguard pigs against PEDV infection.ResultsIn this study, the antiviral efficacy of SP2509, a specific antagonist of Lysine-specific demethylase 1(LSD1), was evaluated in vitro. The RT-qPCR, Western blot, TCID50, and IFA showed that at a concentration of 1µmol/L, SP2509 significantly inhibited PEDV infection. Additionally, viral life cycle assays showed that SP2509 operates by impeding PEDV internalization and replication rather than attachment and release. Regarding mechanism, in Huh-7 cells, knockdowns LSD1 can suppress PEDV replication. This indicated that the inhibition effect of SP2509 on PEDV largely depends on the activity of its target protein, LSD1.ConclusionOur results in vitro show that SP2509 can inhibit PEDV infection during the internalization and replication stage and revealed a role of LSD1 as a restriction factor for PEDV. These imply that LSD1 might be a target for interfering with the viral infection, and SP2509 could be developed as an effective anti-PEDV agent.

A Review on cLF36, a Novel Recombinant Antimicrobial Peptide-Derived Camel Lactoferrin.

Lactoferrin is an antimicrobial peptide (AMP) playing a pivotal role in numerous biological processes. The primary antimicrobial efficacy of lactoferrin is associated with its N-terminal end, which contains various peptides, such as lactoferricin and lactoferrampin. In this context, our research team has developed a refined chimeric 42-mer peptide known as cLF36 over the past few years. This peptide encompasses the complete amino acid sequence of camel lactoferrampin and partial amino acid sequence of lactoferricin. The peptide's activity against human, avian, and plant bacterial pathogens has been assessed using different biological platforms, including prokaryotic (P170 and pET) and eukaryotic (HEK293) expression systems. The peptide positively influenced the growth performance and intestinal morphology of chickens challenged with pathogen bacteria. Computational methods and in vitro studies showed the peptide's antiviral effects against hepatitis C virus, influenza virus, and rotavirus. The chimeric peptide exhibited higher activity against certain tumor cell lines compared to normal cells, which may be attributed to the peptide's interaction with negatively charged glycosaminoglycans on the surface of tumor cells. Importantly, this peptide exhibited no toxicity against host cells and demonstrated remarkable thermal and protease stability in serum. In conclusion, while our investigations suggest that the chimeric peptide, cLF36, may offer potential as a candidate or complementary option to some available antibiotics, antiviral agents, and chemical pesticides, significant uncertainties remain regarding its cost-effectiveness, as well as its pharmacodynamic and pharmacokinetic characteristics, which require further elucidation.

Assessment of pharmacotherapy efficacy for the treatment of exacerbations of chronic obstructive pulmonary disease associated with viral infection

Justification. Knowledge of the differences in response to therapy between phenotypes of exacerbations of chronic obstructive pulmonary disease (COPD) is necessary to improve treatment outcomes. Objective: to determine the most effective additional pharmacological methods for virus-associated exacerbations of COPD. Material and methods. The study included patients hospitalized with exacerbations of COPD with viral (n = 60) and viral-bacterial (n = 60) infections, and a comparison group with exacerbations of COPD with bacterial infection (n = 60). The diagnosis of COPD was based on spirometric criteria, viral infection — according to the results of PCR-RV of sputum for RNA of respiratory viruses. Treatment was carried out in real clinical practice. The groups were comparable in the use of systemic glucocorticoids, short-acting bronchodilators. Dyspnea was assessed using the TDI index (primary endpoint), lung function (spirometry, diffusion capacity for carbon monoxide), exercise tolerance (6-minute walk test), length of hospital stay (secondary endpoints). The сorrelations were determined with the use of Cox proportional hazards model. Results. In the groups with virus-associated and viral-bacterial exacerbations, unlike bacterial exacerbations, the following types of treatment were associated with achieving TDI +1 (odds ratio — OR, 95 % confidence interval — CI): fixed triple combination (OR 2.69; 95 % CI 1.48–4.90; p = 0.010 and OR 2.74; 95 % CI 1.29–3.80; p = 0.031), inhalation of 3 % sodium chloride solution (OR 3.64; 95 % CI 1.45–5.42; p = 0.001 and OR 3.23; 95 % CI 2.15–5.43;\ p = 0.042), antiviral drugs (OR 2.91; 95 % CI 1.15–3.62; p = 0.009 and OR 2.76; 95 % CI 1.31–3.90; p = 0.008). As a result of treatment, an increase in DLco/Va, SpO2 after a 6-minute walk, and a decrease in the length of hospital stay were observed. Conclusion. Detection of virus-associated infections is a promising marker for determining indications for prescribing long-acting anticholinergic drugs and beta-adrenomimetics, inhaled corticosteroids, inhalations of hypertonic sodium chloride solution, and antiviral drugs for exacerbations of COPD.

Severe ocular Mpox in person living with advanced HIV treated with extended course of tecovirimat.

People living with HIV are disproportionately represented among people with severe mpox. Mild and self-limiting conjunctival involvement has been well-documented, and severe ocular complications, including keratitis, corneal scarring, and the associated loss of vision, are increasingly recognized. Tecovirimat is the first-line antiviral therapy for severe mpox, but data around the efficacy of systemic antiviral agents for mpox are limited, particularly in cases of ocular mpox. Here, we describe a case of sight-threatening necrotic blepharokeratoconjunctivitis in a person with advanced HIV, requiring an extended course of tecovirimat due to persistent mpox viral shedding for nearly 5 months.

Design, synthesis and Anti-PVY activity of planar chiral thiourea derivatives incorporated with [2.2]Paracyclophane.

Potato virus Y (PVY) is a prominent representative of plant viruses. It can inflict severe damage upon Solanaceae plants, leading to global dissemination and substantial economic losses. To discover new antiviral agents, a class of planar chiral thiourea molecules through the key step of N-heterocyclic carbene-catalyzed nitrile formation reaction was synthesized with excellent optical purities for antiviral evaluations against plant virus PVY. The absolute configurations of the planar chiral compounds exhibited obvious distinctions in the anti-PVY activities. Notability, compound (S)-4u exhibited remarkable curative activities against PVY, with a half maximal effective concentration (EC50) of 349.3 μg mL-1, which was lower than that of the ningnanmycin (NNM) (EC50 = 400.8 μg mL-1). Additionally, The EC50 value for the protective effects of (S)-4u was 146.2 μg mL-1, which was superior to that of NNM (276.4 μg mL-1). Furthermore, the mechanism-of-action of enantiomers of planar chiral compound 4u was investigated through molecular docking, defensive enzyme activity tests and chlorophyll content tests. Biological mechanism studies have demonstrated that the configuration of planar chiral target compounds plays a crucial role in the molecular interaction with PVY-CP, enhancing the activity of defense enzymes and affecting chlorophyll content. The current study has provided significant insights into the roles played by planar chiralities in plant protection against viruses. This paves the way for the development of novel green pesticides bearing planar chiralities with excellent optical purities. © 2024 Society of Chemical Industry.

Covid-19 A Comprehensive Review of Signs, Symptoms, Diagnosis, and Treatment Strategies

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted global health. This review aims to provide a comprehensive overview of the signs, symptoms, diagnosis, and treatment modalities of COVID-19. The clinical presentation of COVID-19 varies widely, ranging from asymptomatic or mild symptoms to severe respiratory distress and multiorgan failure. Common symptoms include fever, cough, fatigue, and dyspnea, with less frequent symptoms such as anosmia, ageusia, and gastrointestinal symptoms. Diagnosis primarily relies on reverse transcription-polymerase chain reaction (RT-PCR) testing of respiratory specimens. However, imaging modalities such as chest X-ray and Antibody Test Antigen test in diagnosis, especially in cases with atypical presentations. Treatment strategies include supportive care, antiviral therapy, and, in severe cases, and other intensive care measures. The development and distribution of vaccines have been pivotal in controlling the spread of the virus. Despite significant progress in understanding and managing COVID-19, ongoing research is crucial to refine diagnostic strategies, develop effective therapies, and improve patient outcomes. Antiviral drugs, such as remdesivir, poxolovid, molonupiravir, have been widely used to inhibit viral replication and reduce the severity and duration of symptoms. Immunomodulators, including tocilizumab have been used to target specific pathways involved in the hyperinflammatory response seen in severe COVID-19. Monoclonal antibodies, such as casirivimab/imdevimab and sotrovimab, have been employed for passive immunization to neutralize the virus and reduce the risk of severe disease progression

Zingiber officinale-Mediated biosynthesis of bimetallic Gold/Silver (BAu/Ag) nanoalloys; an insight into antiviral and anticancer activities

Utilizing plant extracts in the green synthesis of bimetallic nanoalloys receives more attention due to its eco-friendly, cheap, single-step, easy-handling method, producing highly active and biocompatible nanoalloys. Therefore, the aqueous extract of ginger rhizome was used to form bimetallic gold/silver (Au/Ag) nanoalloys. There were 37.3 mg.g−1 of total soluble carbs, 0.75 mg.g−1 of proteins, and 0.03 mg.g−1 of phenolic compounds quantified in ginger rhizome. The production of BAu/Ag-NPs relies on these components. The as-formed BAu/Ag-NPs were characterized using UV–Vis spectroscopy. The results showed that the peak surface plasmon resonance (SPR) occurred between 440 and 545 nm. The existence of several functional groups involved in the reduction and stability of the generated nanoalloys was shown by Fourier-transform infrared (FT-IR). The nanoalloys, with an average size of 49.1 ± 16.2 nm, were observed to be spherical using transmission electron microscopy (TEM). Energy-dispersive X-ray (EDX) indicated that the synthesized nanoalloy mainly consisted of Au and Ag ions, which made up (31.2 % and 47.1 %) and (45.9 % and 28.6 %) of the sample’s atomic and weight percentages, respectively. The crystallography of the nanoalloys was confirmed using XRD analysis. When examined for their capacity to suppress viral replication, the synthesized nanoalloys showed remarkable results, with 78.2 % inhibition against HAV and 69.6 % against Cox-B4. In addition, the anticancer activity of nanoalloys against oral epithelial cells (OEC), MCF7 adenocarcinoma cells, and HepG2 hepatocarcinoma cells was investigated using the MTT assay method. While the nanoalloys exhibited moderate toxicity towards normal OEC (IC50: 502.5 ± 2.8 g.mL−1), they showed substantial cytotoxicity towards cancer cells, MCF7 and HepG2, with IC50 values of 212.6 ± 4.4 and 117.9 ± 6.6 µg.mL−1, respectively. According to these data, BAu/Ag nanoalloys show potential as antiviral and anticancer drugs that selectively kill cancer cells.

How Much Potential Do Nucleoside Analogs Offer to Combat Human Corona Viruses?

Nucleoside analogs (NAs) have been extensively examined as plausible antiviral agents in recent years, in particular since the outbreak of the global pandemic of COVID-19 in 2019. In this review, the structures and antiviral properties of over 450 NAs are collected according to the type of virus, namely SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-229E, and HCoV-NL63. The activity of the NAs against HCoV-related enzymes is also presented. Selected studies dealing with the mode of action of the NAs are discussed in detail. The repurposing of known NAs appears to be the most extensively investigated scientific approach towards efficacious anti-HCoV agents. The recently reported de novo-designed NAs seem to open up additional approaches to new drug candidates.

Use of antiviral drugs and incidence of Parkinson's disease in Taiwan.

Patients infected with herpes zoster might be at risk for Parkinson's disease (PD). However, antiviral drugs may impede viral deoxyribonucleic acid (DNA) synthesis. This study aimed to determine whether the currently observed association between herpes zoster and PD is consistent with previous findings, and whether antiviral drug use is associated with PD. This retrospective cohort study used the Longitudinal Generation Tracking Database. We included patients aged 40 years and above and applied propensity score matching at 1:1 ratio for study comparability. PD risk was evaluated using Cox proportional hazards regression methods. A total of 234,730 people were analyzed. The adjusted hazard ratio (aHR) for PD in patients with herpes zoster was 1.05. Furthermore, the overall incidence of PD was lower in those treated with antiviral drugs than in the untreated ones (3.17 vs. 3.76 per 1,000 person-years); the aHR was 0.84. After stratifying for sex or age, a similar result was observed. In conclusion, herpes zoster may increase the risk of PD, particularly among females, but receiving antiviral treatment reduces the risk by 16%. Therefore, using antiviral drugs may help prevent PD. However, additional research is required to determine the underlying mechanism(s).