Exploring the antiviral activities of the FDA-approved drug sulfadoxine and its derivatives against Chikungunya virus.

BACKGROUND: Currently, there is no antiviral licensed to treat chikungunya fever, a disease caused by the infection with Alphavirus chikungunya (CHIKV). Treatment is based on analgesic and anti-inflammatory drugs to relieve symptoms. Our study aimed to evaluate the antiviral activity of sulfadoxine (SFX), an FDA-approved drug, and its derivatives complexed with silver(I) (AgSFX), salicylaldehyde Schiff base (SFX-SL), and with both Ag and SL (AgSFX-SL) against CHIKV. METHODS: The anti-CHIKV activity of SFX and its derivatives was investigated using BHK-21 cells infected with CHIKV-nanoluc, a marker virus-carrying nanoluciferase reporter. Dose-response and time of drug-addition assays were performed in order to assess the antiviral effects of the compounds, as well as in silico data and ATR-FTIR analysis for insights on their mechanisms of action. RESULTS: The SFX inhibited 34% of CHIKV replication, while AgSFX, SFX-SL, and AgSFX-SL enhanced anti-CHIKV activity to 84%, 89%, and 95%, respectively. AgSFX, SFX-SL, and AgSFX-SL significantly decreased viral entry and post-entry to host cells, and the latter also protected cells against infection. Additionally, molecular docking calculations and ATR-FTIR analysis demonstrated interactions of SFX-SL, AgSFX, and AgSFX-SL with CHIKV. CONCLUSIONS: Collectively, our findings suggest that the addition of metal ions and/or Schiff base to SFX improved its antiviral activity against CHIKV.

Evaluation of Thiazolidine Derivatives with Potential Anti-ZIKV Activity.

OBJECTIVE: In this study, we have synthesized 19 Thiazolidine (TZD) derivatives to investigate their potential anti-ZIKV effects. METHODS: Nineteen thiazolidine derivatives were synthesized and evaluated for their cytotoxicity and antiviral activity against the ZIKA virus. RESULTS: Among them, six demonstrated remarkable selectivity against the ZIKV virus, exhibiting IC50 values of <5µM, and the other compounds did not demonstrate selectivity for the virus. Interestingly, several derivatives effectively suppressed the replication of ZIKV RNA copies, with derivatives significantly reducing ZIKV mRNA levels at 24 hours post-infection (hpi). Notably, two derivatives (ZKC-4 and -9) stood out by demonstrating a protective effect against ZIKV cell entry. Informed by computational analysis of binding affinity and intermolecular interactions within the NS5 domain's N-7 and O'2 positions, ZKC-4 and FT-39 displayed the highest predicted affinities. Intriguingly, ZKC-4 and ZKC-9 derivatives exhibited the most favorable predicted binding affinities for the ZIKV-E binding site. CONCLUSION: The significance of TZDs as potent antiviral agents is underscored by these findings, suggesting that exploring TZD derivatives holds promise for advancing antiviral therapeutic strategies.

A mimetic peptide of ACE2 protects against SARS-CoV-2 infection and decreases pulmonary inflammation related to COVID-19.

Since human angiotensin-converting enzyme 2 (ACE2) serves as a primary receptor for SARS-CoV-2, characterizing ACE2 regions that allow SARS-CoV-2 to enter human cells is essential for designing peptide-based antiviral blockers and elucidating the pathogenesis of the virus. We identified and synthesized a 25-mer mimetic peptide (encompassing positions 22-46 of the ACE2 alpha-helix α1) implicated in the S1 receptor-binding domain (RBD)-ACE2 interface. The mimetic (wild-type, WT) ACE2 peptide significantly inhibited SARS-CoV-2 infection of human pulmonary Calu-3 cells in vitro. In silico protein modeling predicted that residues F28, K31, F32, F40, and Y41 of the ACE2 alpha-helix α1 are critical for the original, Delta, and Omicron strains of SARS-CoV-2 to establish the Spike RBD-ACE2 interface. Substituting these residues with alanine (A) or aspartic acid (D) abrogated the antiviral protective effect of the peptides, indicating that these positions are critical for viral entry into pulmonary cells. WT ACE2 peptide, but not the A or D mutated peptides, exhibited significant interaction with the SARS-CoV-2 S1 RBD, as shown through molecular dynamics simulations. Through identifying the critical amino acid residues of the ACE2 alpha-helix α1, which is necessary for the Spike RBD-ACE2 interface and mobilized during the in vitro viral infection of cells, we demonstrated that the WT ACE2 peptide protects susceptible K18-hACE2 mice against in vivo SARS-CoV-2 infection and is effective for the treatment of COVID-19.

Taming the storm: potential anti-inflammatory compounds targeting SARS-CoV-2 MPro.

In severe COVID-19 cases, an exacerbated inflammatory response triggers a cytokine storm that can worsen the prognosis. Compounds with both antiviral and anti-inflammatory activities show promise as candidates for COVID-19 therapy, as they potentially act against the SARS-CoV-2 infection regardless of the disease stage. One of the most attractive drug targets among coronaviruses is the main protease (MPro). This enzyme is crucial for cleaving polyproteins into non-structural proteins required for viral replication. The aim of this review was to identify SARS-CoV-2 MPro inhibitors with both antiviral and anti-inflammatory properties. The interactions of the compounds within the SARS-CoV-2 MPro binding site were analyzed through molecular docking when data from crystallographic structures were unavailable. 18 compounds were selected and classified into five different superclasses. Five of them exhibit high potency against MPro: GC-376, baicalein, naringenin, heparin, and carmofur, with IC50 values below 0.2 µM. The MPro inhibitors selected have the potential to alleviate lung edema and decrease cytokine release. These molecules mainly target three critical inflammatory pathways: NF-κB, JAK/STAT, and MAPK, all previously associated with COVID-19 pathogenesis. The structures of the compounds occupy the S1/S2 substrate binding subsite of the MPro. They interact with residues from the catalytic dyad (His41 and Cys145) and/or with the oxyanion hole (Gly143, Ser144, and Cys145), which are pivotal for substrate recognition. The MPro SARS-CoV-2 inhibitors with potential anti-inflammatory activities present here could be optimized for maximum efficacy and safety and be explored as potential treatment of both mild and severe COVID-19.

Antiviral action of aqueous extracts of propolis from Scaptotrigona aff. postica (Hymenoptera; Apidae) against Zica, Chikungunya, and Mayaro virus.

The limited availability of antivirals for new highly pathogenic strains of virus has become a serious public health. Therefore, news products against these pathogens has become an urgent necessity. Among the multiple sources for news antibiotics and antivirals, insect exudates or their products has become an increasingly frequent option. Insects emerged 350 million years ago and have showed a high adaptability and resistance to the most varied biomes. Their survival for so long, in such different environments, is an indication that they have a very efficient protection against environmental infections, despite not having a developed immune system like mammals. Since the ancient civilizations, the products obtained from the bee have been of great pharmacological importance, being used as antimicrobial, anti-inflammatory, antitumor and several other functions. Investigations of biological activity of propolis have been carried out, mainly in the species Apis mellifera, and its product have showed activity against some important viruses. However, for the Meliponini species, known as stingless bees, there are few studies, either on their chemical composition or on their biological activities. The importance of studying these bees is because they come from regions with native forests, and therefore with many species of plants not yet studied, in addition to which they are regions still free of pesticides, which guarantees a greater fidelity of the obtained data. Previous studies by our group with crude hydroalcoholic extract of propolis demonstrated an intense antiviral activity against Herpes, influenza, and rubella viruses. In this work, we chose to use aqueous extracts, which eliminates the presence of other compounds besides those originally present in propolis, in addition to extracting substances different from those obtained in alcoholic extracts. Therefore, this study aimed to identify, isolate and characterize compounds with antiviral effects from aqueous propolis extracts from Scaptotrigona aff postica, in emerging viruses such as zicavirus, chikungunya, and mayaro virus. The evaluation of the antiviral activity of the crude and purified material was performed by reducing infectious foci in VERO cell cultures. The results obtained with crude propolis, indicate a high reduction of zica virus (64×) and mayaro (128×) when was used 10% v/v of propolis. The reduction of chikungunya virus was of 256 fold, even when was used 5% v/v of propolis. The chemical characterization of the compounds present in the extracts was performed by high-pressure liquid chromatography. Through the purification of propolis by HPLC and mass spectrometry, it was possible to identify and isolate a peak with antiviral activity. This substance showed activity against all viruses tested. When purified fraction was used, the reduction observed was of 16 fold for zicavirus, 32 fold for mayaro virus and 512 fold for chikungunya virus. Likewise, it was observed that the antiviral response was concentration dependent, being more intense when propolis was added 2 h after the viral infection. Now we are carrying out the chemical characterization of the purified compounds that showed antiviral action.

Cyanobacterial and microalgae polymers: antiviral activity and applications.

At the end of 2019, the world witnessed the beginning of the COVID-19 pandemic. As an aggressive viral infection, the entire world remained attentive to new discoveries about the SARS-CoV-2 virus and its effects in the human body. The search for new antivirals capable of preventing and/or controlling the infection became one of the main goals of research during this time. New biocompounds from marine sources, especially microalgae and cyanobacteria, with pharmacological benefits, such as anticoagulant, anti-inflammatory and antiviral attracted particular interest. Polysaccharides (PS) and extracellular polymeric substances (EPS), especially those containing sulfated groups in their structure, have potential antiviral activity against several types of viruses including HIV-1, herpes simplex virus type 1, and SARS-CoV-2. We review the main characteristics of PS and EPS with antiviral activity, the mechanisms of action, and the different extraction methodologies from microalgae and cyanobacteria biomass.

The Mechanism of Action of L-Tyrosine Derivatives against Chikungunya Virus Infection In Vitro Depends on Structural Changes.

Although the disease caused by chikungunya virus (CHIKV) is of great interest to public health organizations around the world, there are still no authorized antivirals for its treatment. Previously, dihalogenated anti-CHIKV compounds derived from L-tyrosine (dH-Y) were identified as being effective against in vitro infection by this virus, so the objective of this study was to determine the mechanisms of its antiviral action. Six dH-Y compounds (C1 to C6) dihalogenated with bromine or chlorine and modified in their amino groups were evaluated by different in vitro antiviral strategies and in silico tools. When the cells were exposed before infection, all compounds decreased the expression of viral proteins; only C4, C5 and C6 inhibited the genome; and C1, C2 and C3 inhibited infectious viral particles (IVPs). Furthermore, C1 and C3 reduce adhesion, while C2 and C3 reduce internalization, which could be related to the in silico interaction with the fusion peptide of the E1 viral protein. Only C3, C4, C5 and C6 inhibited IVPs when the cells were exposed after infection, and their effect occurred in late stages after viral translation and replication, such as assembly, and not during budding. In summary, the structural changes of these compounds determine their mechanism of action. Additionally, C3 was the only compound that inhibited CHIKV infection at different stages of the replicative cycle, making it a compound of interest for conversion as a potential drug.

Development and validation of Mayaro virus with luciferase reporter genes as a tool for antiviral assays.

Arboviruses are etiological agents in an extensive group of emerging diseases with great clinical relevance in Brazil, due to the wide distribution of their vectors and the favorable environmental conditions. Among them, the Mayaro virus (MAYV) has drawn attention since its emergence as the etiologic agent of Mayaro fever, a highly debilitating disease. To study viral replication and identify new drug candidates, traditional antiviral assays based on viral antigens and/or plaque assays have been demonstrating low throughput, making it difficult to carry out larger-scale assays. Therefore, we developed and characterized two DNA-launched infectious clones reporter viruses based on the MAYV strain BeAr 20290 containing the reporter genes of firefly luciferase (FLuc) and nanoluciferase (NLuc), designated as MAYV-firefly and MAYV-nanoluc, respectively. The viruses replicated efficiently with similar properties to the parental wild-type MAYV, and luminescence expression levels reflected viral replication. Reporter genes were also preserved during passage in cell culture, remaining stably expressed for one round of passage for MAYV-firefly and three rounds for MAYV-nanoluc. Employing the infectious clone, we described the effect of Rimantadine, an FDA-approved Alzheimer's drug, as a repurposing agent for MAYV but with a broad-spectrum activity against Zika virus infection. Additionally, we validated MAYV-nanoluc as a tool for antiviral drug screening using the compound EIDD-2749 (4'-Fluorouridine), which acts as an inhibitor of alphavirus RNA-dependent RNA polymerase.

Antiviral Activities of Mastoparan-L-Derived Peptides against Human Alphaherpesvirus 1.

Human alphaherpesvirus 1 (HSV-1) is a significantly widespread viral pathogen causing recurrent infections that are currently incurable despite available treatment protocols. Studies have highlighted the potential of antimicrobial peptides sourced from Vespula lewisii venom, particularly those belonging to the mastoparan family, as effective against HSV-1. This study aimed to demonstrate the antiviral properties of mastoparans, including mastoparan-L [I5, R8], mastoparan-MO, and [I5, R8] mastoparan, against HSV-1. Initially, Vero cell viability was assessed in the presence of these peptides, followed by the determination of antiviral activity, mechanism of action, and dose-response curves through plaque assays. Structural analyses via circular dichroism and nuclear magnetic resonance were conducted, along with evaluating membrane fluidity changes induced by [I5, R8] mastoparan using fluorescence-labeled lipid vesicles. Cytotoxic assays revealed high cell viability (>80%) at concentrations of 200 µg/mL for mastoparan-L and mastoparan-MO and 50 µg/mL for [I5, R8] mastoparan. Mastoparan-MO and [I5, R8] mastoparan exhibited over 80% HSV-1 inhibition, with up to 99% viral replication inhibition, particularly in the early infection stages. Structural analysis indicated an α-helical structure for [I5, R8] mastoparan, suggesting effective viral particle disruption before cell attachment. Mastoparans present promising prospects for HSV-1 infection control, although further investigation into their mechanisms is warranted.

Sofosbuvir Off-label Treatment of Yellow Fever Patients During an Outbreak in Brazil, 2018: A Cohort Study.

We enrolled 21 patients with laboratory-confirmed yellow fever (YF), hospitalized at Eduardo de Menezes Hospital, Brazil, to be treated with sofosbuvir, a drug approved for hepatitis C. Given the absence of specific YF antiviral treatments, the off-label nonrandomized sofosbuvir treatment aimed to address high disease severity and the risk of fatal outcomes. Patients received a daily dose of 400 mg sofosbuvir from 4 to 10 days post-symptom onset. YF viral load (VL) comparisons were made between treated and nontreated patients who either survived or died. The genomic VL for the treated group steadily decreased after day 7 post-symptom onset, suggesting that sofosbuvir might reduce YF VL. This study underscores the urgent need for YF antiviral therapies, advocating for randomized clinical trials to further explore sofosbuvir's role in YF treatment.

T cell-mediated Immune response and correlates of inflammation and their relationship with COVID-19 clinical severity: not an intuitive guess.

BACKGROUND: Predictors of the outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remain to be fully determined. We evaluated selected viral characteristics and immunological responses that might predict and/or correlate to the clinical outcome of COVID-19. METHODS: For individuals developing divergent clinical outcomes, the magnitude and breadth of T cell-mediated responses were measured within 36 h of symptom onset. Peripheral Blood Mononuclear Cells (PBMCs) were subjected to in vitro stimulation with SARS-CoV-2-based peptides. In addition, SARS-CoV-2 sequences were generated by metagenome, and HLA typing was performed using Luminex technology. FINDINGS: CD4+ T cell activation was negatively correlated with SARS-CoV-2 basal viral load in patients with severe COVID-19 (p = 0·043). The overall cellular immune response, as inferred by the IFN-γ signal, was higher at baseline for patients who progressed to mild disease compared to patients who progressed to severe disease (p = 0·0044). Subjects with milder disease developed higher T cell responses for MHC class I and II-restricted peptides (p = 0·033). INTERPRETATION: Mounting specific cellular immune responses in the first days after symptom onset, as inferred by IFN-γ magnitude in the ELISPOT assay, may efficiently favor a positive outcome. In contrast, progression to severe COVID-19 was accompanied by stronger cellular immune responses, higher CD4 + T cell activation, and a higher number of in silico predicted high-affinity class I HLA alleles.

Current challenges in the discovery of treatments against Mayaro fever.

INTRODUCTION: Mayaro fever is an emerging viral disease that manifests as an acute febrile illness. The disease is self-limiting, however joint pain can persist for months leading to chronic arthralgia. There is no specific treatment available, which ultimately leads to socioeconomic losses in populations at risk as well as strains to the public health systems. AREAS COVERED: We reviewed the candidate treatments proposed for Mayaro virus (MAYV) infection and disease, including antiviral compounds targeting viral or host mechanisms, and pathways involved in disease development and pathogenicity. We assessed compound screening technologies and experimental infection models used in these studies and indicated the advantages and limitations of available technologies and intended therapeutic strategies. EXPERT OPINION: Although several compounds have been suggested as candidate treatments against MAYV infection, notably those with antiviral activity, most compounds were assessed only in vitro. Compounds rarely progress toin vivo or preclinical studies, and such difficulty may be associated with limited experimental models. MAYV biology is largely inferred from related alphaviruses and reflected by few studies focusing on target proteins or mechanisms of action for MAYV. Therapeutic strategies targeting pathogenic inflammatory responses have shown potential against MAYV-induced disease in vivo, which might reduce long-term sequelae.

Antiviral Activity of Kappaphycus alvarezii Seaweed against ZIKV.

INTRODUCTION: Zika virus (ZIKV) is a flavivirus transmitted through the bites of infected Aedes mosquitoes. These viruses can also be transmitted through sexual contact, vertical transmission, and possibly transfusion. Most cases are asymptomatic, but symptoms can include rash, conjunctivitis, fever, and arthralgia, which are characteristic of other arboviruses. Zika infection can lead to complications such as microcephaly, miscarriage, brain abnormalities, and Guillain-Barré syndrome (GBS). OBJECTIVE: The aim is to determine the inhibitory potential of the algae Kappaphycus alvarezii (K. alvarezii) on ZIKV replication. METHODOLOGY: Cytotoxicity experiments were performed using Vero cells to determine the CC50, and ZIKV replication inhibition assays (ATCC® VR-1839™) were conducted to determine the EC50. The mechanism of action was also studied to assess any synergistic effect with Ribavirin. RESULTS: K. alvarezii demonstrated low toxicity with a CC50 of 423 µg/mL and a potent effect on ZIKV replication with an EC50 of 0.65 µg/mL and a Selectivity Index (SI) of 651, indicating the extract's safety. Virucidal effect assays were carried out to evaluate the possible mechanism of action, and the compound addition time was studied, showing the potential to delay the treatment of infected cells by up to 6 hours. A potential synergistic effect was observed when K. alvarezii extract was combined with suboptimal concentrations of Ribavirin, resulting in 99% inhibition of viral replication. CONCLUSION: Our data demonstrate the significant potential of K. alvarezii extract and highlight the need for further studies to investigate its mechanism of action. We propose this extract as a potential anti-Zika compound.

The search for an antiviral lead molecule to combat the neglected emerging Oropouche virus.

Oropouche virus (OROV) is a member of the Peribunyaviridae family and the causative agent of a dengue-like febrile illness transmitted by mosquitoes. Although mild symptoms generally occur, complications such as encephalitis and meningitis may develop. A lack of proper diagnosis, makes it a potential candidate for new epidemics and outbreaks like other known arboviruses such as Dengue, Yellow Fever and Zika virus. The study of natural molecules as potential antiviral compounds is a promising alternative for antiviral therapies. Wedelolactone (WDL) has been demonstrated to inhibit some viral proteins and virus replication, making it useful to target a wide range of viruses. In this study, we report the in silico effects of WDL on the OROV N-terminal polymerase and its potential inhibitory effects on several steps of viral infection in mammalian cells in vitro, which revealed that WDL indeed acts as a potential inhibitor molecule against OROV infection.

Arylamines QSAR-Based Design and Molecular Dynamics of New Phenylthiophene and Benzimidazole Derivatives with Affinity for the C111, Y268, and H73 Sites of SARS-CoV-2 PLpro Enzyme.

A non-structural SARS-CoV-2 protein, PLpro, is involved in post-translational modifications in cells, allowing the evasion of antiviral immune response mechanisms. In this study, potential PLpro inhibitory drugs were designed using QSAR, molecular docking, and molecular dynamics. A combined QSAR equation with physicochemical and Free-Wilson descriptors was formulated. The r2, q2, and r2test values were 0.833, 0.770, and 0.721, respectively. From the equation, it was found that the presence of an aromatic ring and a basic nitrogen atom is crucial for obtaining good antiviral activity. Then, a series of structures for the binding sites of C111, Y268, and H73 of PLpro were created. The best compounds were found to exhibit pIC50 values of 9.124 and docking scoring values of -14 kcal/mol. The stability of the compounds in the cavities was confirmed by molecular dynamics studies. A high number of stable contacts and good interactions over time were exhibited by the aryl-thiophenes Pred14 and Pred15, making them potential antiviral candidates.

Interleukin 27, like interferons, activates JAK-STAT signaling and promotes pro-inflammatory and antiviral states that interfere with dengue and chikungunya viruses replication in human macrophages.

Interferons (IFNs) are a family of cytokines that activate the JAK-STAT signaling pathway to induce an antiviral state in cells. Interleukin 27 (IL-27) is a member of the IL-6 and/or IL-12 family that elicits both pro- and anti-inflammatory responses. Recent studies have reported that IL-27 also induces a robust antiviral response against diverse viruses, both in vitro and in vivo, suggesting that IFNs and IL-27 share many similarities at the functional level. However, it is still unknown how similar or different IFN- and IL-27-dependent signaling pathways are. To address this question, we conducted a comparative analysis of the transcriptomic profiles of human monocyte-derived macrophages (MDMs) exposed to IL-27 and those exposed to recombinant human IFN-α, IFN-γ, and IFN-λ. We utilized bioinformatics approaches to identify common differentially expressed genes between the different transcriptomes. To verify the accuracy of this approach, we used RT-qPCR, ELISA, flow cytometry, and microarrays data. We found that IFNs and IL-27 induce transcriptional changes in several genes, including those involved in JAK-STAT signaling, and induce shared pro-inflammatory and antiviral pathways in MDMs, leading to the common and unique expression of inflammatory factors and IFN-stimulated genes (ISGs)Importantly, the ability of IL-27 to induce those responses is independent of IFN induction and cellular lineage. Additionally, functional analysis demonstrated that like IFNs, IL-27-mediated response reduced chikungunya and dengue viruses replication in MDMs. In summary, IL-27 exhibits properties similar to those of all three types of human IFN, including the ability to stimulate a protective antiviral response. Given this similarity, we propose that IL-27 could be classified as a distinct type of IFN, possibly categorized as IFN-pi (IFN-π), the type V IFN (IFN-V).

Nanostructured lipid carriers loaded with essential oils: a strategy against SARS-CoV-2.

This work aimed to investigate the effectiveness of Lippia sidoides and Syzygium aromaticum essential oils (EOs) encapsulated in nanostructured lipid carriers (NLCs) as SARS-CoV-2 inhibitors through virucidal activity assessment. We developed anionic and cationic NLCs loaded with the EOs and assessed their physicochemical properties and SARS-CoV-2 virucidal activity, focusing on the effects of EO type and the NLCs composition. The NLCs exhibited particle sizes of 141.30 to 160.53 nm for anionic and 109.30 to 138.60 nm for cationic types, with PDIs between 0.16 and 0.25. High zeta potentials (>29.0 in modulus) indicated stable formulations. The NLCs effectively encapsulated the EOs, achieving encapsulation efficiencies between 84.6 to 100% w/w of marker compound. The EOs-loaded NLCs reduced the SARS-CoV-2 virion count, exceeding 2 logs over the control. NLCs loaded with Lippia sidoides and Syzygium aromaticum EOs represent an innovative strategy for combating SARS-CoV-2.

Virus adsorbent systems based on Amazon holocellulose and nanomaterials.

The environment preservation has been an important motivation to find alternative, functional, and biodegradable materials to replace polluting petrochemicals. The production of nonbiodegradable face masks increased the concentration of microplastics in the environment, highlighting the need for sustainable alternatives, such as the use of local by-products to create efficient and eco-friendly filtering materials. Furthermore, the use of smart materials can reduce the risk of contagion and virus transmission, especially in the face of possible mutations. The development of novel materials is necessary to ensure less risk of contagion and virus transmission, as well as to preserve the environment. Taking these factors into account, 16 systems were developed with different combinations of precursor materials (holocellulose, polyaniline [ES-PANI], graphene oxide [GO], silver nanoparticles [AgNPs], and activated carbon [AC]). Adsorption tests of the spike protein showed that the systems containing GO and AC were the most efficient in the adsorption process. Similarly, plate tests conducted using the VSV-IN strain cultured in HepG2 cells showed that the system containing all phases showed the greatest reduction in viral titer method. In agreement, the biocompatibility tests showed that the compounds extracted from the systems showed low cytotoxicity or no significant cytotoxic effect in human fibroblasts. As a result, the adsorption tests of the spike protein, viral titration, and biocompatibility tests showed that systems labeled as I and J were the most efficient. In this context, the present research has significantly contributed to the technological development of antiviral systems, with improved properties and increased adsorption efficiency, reducing the viral titer and contributing efficiently to public health. In this way, these alternative materials could be employed in sensors and devices for filtering and sanitization, thus assisting in mitigating the transmission of viruses and bacteria. RESEARCH HIGHLIGHTS: Sixteen virus adsorbent systems were developed with different combinations of precursor materials (holocellulose, polyaniline (ES-PANI), graphene oxide (GO), silver nanoparticles (AgNPs), and activated carbon (AC)). The system that included all of the nanocomposites holocellulose, PANI, GO, AgNPs, and AC showed the greatest reduction in viral titration. The biocompatibility tests revealed that all systems caused only mild or moderate cytotoxicity toward human fibroblasts.

Influence of diimine bidentate ligand in the nitrosyl and nitro terpyridine ruthenium complex on the HSA/DNA interaction and antiviral activity.

Nitric oxide (NO) acts in different physiological processes, such as blood pressure control, antiparasitic activities, neurotransmission, and antitumor action. Among the exogenous NO donors, ruthenium nitrosyl/nitro complexes are potential candidates for prodrugs, due to their physicochemical properties, such as thermal and physiological pH stability. In this work, we proposed the synthesis and physical characterization of the new nitro terpyridine ruthenium (II) complexes of the type [RuII(L)(NO2)(tpy)]PF6 where tpy = 2,2':6',2″-terpyridine; L = 3,4-diaminobenzoic acid (bdq) or o-phenylenediamine (bd) and evaluation of influence of diimine bidentate ligand NH.NHq-R (R = H or COOH) in the HSA/DNA interaction as well as antiviral activity. The interactions between HSA and new nitro complexes [RuII(L)(NO2)(tpy)]+ were evaluated. The Ka values for the HSA-[RuII(bdq)(NO2)(tpy)]+ is 10 times bigger than HSA-[RuII(bd)(NO2)(tpy)]+. The sites of interaction between HSA and the complexes via synchronous fluorescence suppression indicate that the [RuII(bdq)(NO2)(tpy)]+ is found close to the Trp-241 residue, while the [RuII(bd)(NO2)(tpy)]+ complex is close to Tyr residues. The interaction with fish sperm fs-DNA using direct spectrophotometric titration (Kb) and ethidium bromide replacement (KSV and Kapp) showed weak interaction in the system fs-DNA-[RuII(bdq)(NO)(tpy)]+. Furthermore, fs-DNA-[RuII(bd)(NO2)(tpy)]+ and fs-DNA-[RuII(bd)(NO)(tpy)]3+ system showed higher intercalation constant. Circular dichroism spectra for fs-DNA-[RuII(bd)(NO2)(tpy)]+ and fs-DNA-[RuII(bd)(NO)(tpy)]3+, suggest semi-intercalative accompanied by major groove binding interaction modes. The [RuII(bd)(NO2)(tpy)]+ and [RuII(bd)(NO)(tpy)]3+ inhibit replication of Zika and Chikungunya viruses based in the nitric oxide release under S-nitrosylation reaction with cysteine viral.

Curcumin and quercetin co-encapsulated in nanoemulsions for nasal administration: A promising therapeutic and prophylactic treatment for viral respiratory infections.

One of the most frequent causes of respiratory infections are viruses. Viruses reaching the airways can be absorbed by the human body through the respiratory mucosa and mainly infect lung cells. Several viral infections are not yet curable, such as coronavirus-2 (SARS-CoV-2). Furthermore, the side effect of synthetic antiviral drugs and reduced efficacy against resistant variants have reinforced the search for alternative and effective treatment options, such as plant-derived antiviral molecules. Curcumin (CUR) and quercetin (QUE) are two natural compounds that have been widely studied for their health benefits, such as antiviral and anti-inflammatory activity. However, poor oral bioavailability limits the clinical applications of these natural compounds. In this work, nanoemulsions (NE) co-encapsulating CUR and QUE designed for nasal administration were developed as promising prophylactic and therapeutic treatments for viral respiratory infections. The NEs were prepared by high-pressure homogenization combined with the phase inversion temperature technique and evaluated for their physical and chemical characteristics. In vitro assays were performed to evaluate the nanoemulsion retention into the porcine nasal mucosa. In addition, the CUR and QUE-loaded NE antiviral activity was tested against a murine ß-COV, namely MHV-3. The results evidenced that CUR and QUE loaded NE had a particle size of 400 nm and retention in the porcine nasal mucosa. The antiviral activity of the NEs showed a percentage of inhibition of around 99 %, indicating that the developed NEs has interesting properties as a therapeutic and prophylactic treatment against viral respiratory infections.