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.

Diminazene aceturate inhibits the SARS-CoV-2 spike protein-induced inflammation involving leukocyte migration and DNA extracellular traps formation.

AIMS: To investigate the SARS-CoV-2 Spike protein (Spk)-induced inflammatory response and its downmodulation by diminazene aceturate (DIZE). MATERIALS AND METHODS: Through inducing Spk inflammation in murine models, leukocyte migration to the peritoneum, levels of myeloperoxidase (MPO), malondialdehyde (MDA), rolling and adhesion of mesenteric leukocytes, and vascular permeability were investigated. Extracellular DNA traps (DETs) induced by Spk and the production of IL-6 and TNF-α were analyzed using human neutrophils, monocytes, and macrophages. In silico assays assessed the molecular interaction between DIZE and molecules related to leukocyte migration and DETs induction. KEY FINDINGS: Spk triggered acute inflammation, demonstrated by increasing leukocyte migration. Oxidative stress was evidenced by elevated levels of MPO and MDA in the peritoneal liquid. DIZE attenuated cell migration, rolling, and leukocyte adhesion, improved vascular barrier function, mitigated DETs, and reduced the production of Spk-induced pro-inflammatory cytokines. Computational studies supported our findings, showing the molecular interaction of DIZE with targets such as ß2 integrin, PI3K, and PAD2 due to its intermolecular coupling. SIGNIFICANCE: Our results outline a novel role of DIZE as a potential therapeutic agent for mitigating Spk-induced inflammation.

In Silico Comparative Analysis of Ivermectin and Nirmatrelvir Inhibitors Interacting with the SARS-CoV-2 Main Protease.

Exploring therapeutic options is crucial in the ongoing COVID-19 pandemic caused by SARS-CoV-2. Nirmatrelvir, which is a potent inhibitor that targets the SARS-CoV-2 Mpro, shows promise as an antiviral treatment. Additionally, Ivermectin, which is a broad-spectrum antiparasitic drug, has demonstrated effectiveness against the virus in laboratory settings. However, its clinical implications are still debated. Using computational methods, such as molecular docking and 100 ns molecular dynamics simulations, we investigated how Nirmatrelvir and Ivermectin interacted with SARS-CoV-2 Mpro(A). Calculations using density functional theory were instrumental in elucidating the behavior of isolated molecules, primarily by analyzing the frontier molecular orbitals. Our analysis revealed distinct binding patterns: Nirmatrelvir formed strong interactions with amino acids, like MET49, MET165, HIS41, HIS163, HIS164, PHE140, CYS145, GLU166, and ASN142, showing stable binding, with a root-mean-square deviation (RMSD) of around 2.0 Å. On the other hand, Ivermectin interacted with THR237, THR239, LEU271, LEU272, and LEU287, displaying an RMSD of 1.87 Å, indicating enduring interactions. Both ligands stabilized Mpro(A), with Ivermectin showing stability and persistent interactions despite forming fewer hydrogen bonds. These findings offer detailed insights into how Nirmatrelvir and Ivermectin bind to the SARS-CoV-2 main protease, providing valuable information for potential therapeutic strategies against COVID-19.

Rational Approach toward COVID-19's Main Protease Inhibitors: A Hierarchical Biochemoinformatics Analysis.

This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 Mpro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for Mpro, ranging from -6.2 to -9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein-ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and Mpro, with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with Mpro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.

Takotsubo syndrome as an outcome of the use of checkpoint inhibitor therapy in patients with COVID-19.

Takotsubo Syndrome (TS) is a heart disease caused by extreme exposure of the body to physical or psychological stress. In the context of COVID-19, the virus can be a significant source of stress, with particular attention being paid to the cytokine storm as a cause of damage to the body. New research shows that the production of specific cytokines is linked to the activation of immune checkpoint proteins such as PD-1, PD-L1, and CTLA-4 on T cells. Although initially beneficial in combating infections, it can suppress defense and aid in disease progression. Therefore, checkpoint inhibitor therapy has been highlighted beyond oncological therapies, given its effectiveness in strengthening the immune system. However, this treatment can lead to excessive immune responses, inflammation, and stress on the heart, which can cause Takotsubo Syndrome in patients. Several studies investigate the direct link between this therapy and cardiac injuries in these patients, which can trigger TS. From this perspective, we must delve deeper into this treatment and consider its effects on the prognosis against SARS-CoV-2 infection.

Enhancing pulmonary delivery and immunomodulation of respiratory diseases through virus-mimicking nanoparticles.

This study introduces the nanobromhexine lipid particle (NBL) platform designed for effective pulmonary drug delivery. Inspired by respiratory virus transport mechanisms, NBL address challenges associated with mucus permeation and inflammation in pulmonary diseases. Composed of low molecular weight polyethylene glycol-coated lipid nanoparticles with bromhexine hydrochloride, NBL exhibit a size of 118 ± 24 nm, a neutral zeta potential, osmolarity of 358 ± 28 mOsmol/kg, and a pH of 6.5. Nebulizing without leakage and showing no toxicity to epithelial cells, NBL display mucoadhesive properties with a 60% mucin-binding efficiency. They effectively traverse the dense mucus layer of Calu-3 cultures in an air-liquid interface, as supported by a 55% decrease in MUC5AC density and a 29% increase in nanoparticles internalization compared to non-exposed cells. In assessing immunomodulatory effects, NBL treatment in SARS-CoV-2-infected lung cells leads to a 40-fold increase in anti-inflammatory MUC1 gene expression, a proportional reduction in pro-inflammatory IL-6 expression, and elevated anti-inflammatory IL-10 expression. These findings suggest a potential mechanism to regulate the excessive IL-6 expression triggered by virus infection. Therefore, the NBL platform demonstrates promising potential for efficient pulmonary drug delivery and immunomodulation, offering a novel approach to addressing mucus permeation and inflammation in pulmonary diseases.

Targeting GPVI with glenzocimab in COVID-19 patients: Results from a randomized clinical trial.

BACKGROUND: Glenzocimab is a novel antithrombotic agent which targets platelet glycoprotein VI (GPVI) and does not induce haemorrhage. SARS-CoV-2 triggers a prothrombotic state and lung injury whose mechanisms include coagulopathy, endothelial dysfunction, and inflammation with dysregulated platelets. METHODS AND PATIENTS: GARDEN was a randomised double-blind, exploratory phase II study of glenzocimab in SARS-CoV-2 respiratory failure (NCT04659109). PCR+ adults in Brazil and France (7 centres) were randomized to standard-of-care (SOC) plus glenzocimab (1000 mg/dayx3 days) or placebo, followed for 40 days. Primary efficacy endpoint was clinical progression at Day 4. All analyses concerned the intention-to-treat population. RESULTS: Between December 2020 and August 2021, 61 patients received at least one dose (30 glenzocimab vs 32 placebo) and 58 completed the study (29 vs 29). Clinical progression of COVID-19 ARDS was not statistically different between glenzocimab and placebo arms (43.3% and 29.0%, respectively; p = 0.245). Decrease in the NEWS-2 category at D4 was statistically significant (p = 0.0290) in the glenzocimab arm vs placebo. No Serious Adverse Event (SAE) was deemed related to study drug; bleeding related events were reported in 6 patients (7 events) and 4 patients (4 events) in glenzocimab and placebo arms, respectively. CONCLUSIONS: Therapeutic GPVI inhibition assessment during COVID-19 was conducted in response to a Public Health emergency. Glenzocimab in coagulopathic patients under therapeutic heparin was neither associated with increased bleeding, nor SAE. Clinical impact of glenzocimab on COVID-19 ARDS was not demonstrated. A potential role for GPVI inhibition in other types of ARDS deserves further experimentation. Glenzocimab is currently studied in stroke (ACTISAVE: NCT05070260) and cardiovascular indications.

The Malaria Box molecules: a source for targeting the RBD and NTD cryptic pocket of the spike glycoprotein in SARS-CoV-2.

CONTEXT: SARS-CoV-2, responsible for COVID-19, has led to over 500 million infections and more than 6 million deaths globally. There have been limited effective treatments available. The study aims to find a drug that can prevent the virus from entering host cells by targeting specific sites on the virus's spike protein. METHOD: We examined 13,397 compounds from the Malaria Box library against two specific sites on the spike protein: the receptor-binding domain (RBD) and a predicted cryptic pocket. Using virtual screening, molecular docking, molecular dynamics, and MMPBSA techniques, they evaluated the stability of two compounds. TCMDC-124223 showed high stability and binding energy in the RBD, while TCMDC-133766 had better binding energy in the cryptic pocket. The study also identified that the interacting residues are conserved, which is crucial for addressing various virus variants. The findings provide insights into the potential of small molecules as drugs against the spike protein.

3-Chymotrypsin-like Protease (3CLpro) of SARS-CoV-2: Validation as a Molecular Target, Proposal of a Novel Catalytic Mechanism, and Inhibitors in Preclinical and Clinical Trials.

Proteases represent common targets in combating infectious diseases, including COVID-19. The 3-chymotrypsin-like protease (3CLpro) is a validated molecular target for COVID-19, and it is key for developing potent and selective inhibitors for inhibiting viral replication of SARS-CoV-2. In this review, we discuss structural relationships and diverse subsites of 3CLpro, shedding light on the pivotal role of dimerization and active site architecture in substrate recognition and catalysis. Our analysis of bioinformatics and other published studies motivated us to investigate a novel catalytic mechanism for the SARS-CoV-2 polyprotein cleavage by 3CLpro, centering on the triad mechanism involving His41-Cys145-Asp187 and its indispensable role in viral replication. Our hypothesis is that Asp187 may participate in modulating the pKa of the His41, in which catalytic histidine may act as an acid and/or a base in the catalytic mechanism. Recognizing Asp187 as a crucial component in the catalytic process underscores its significance as a fundamental pharmacophoric element in drug design. Next, we provide an overview of both covalent and non-covalent inhibitors, elucidating advancements in drug development observed in preclinical and clinical trials. By highlighting various chemical classes and their pharmacokinetic profiles, our review aims to guide future research directions toward the development of highly selective inhibitors, underscore the significance of 3CLpro as a validated therapeutic target, and propel the progression of drug candidates through preclinical and clinical phases.

Skin- and Eco-Friendly Hand Sanitizer: A Novel Composition of Natural Extracts to Prevent the Spread of Respiratory Viruses.

Respiratory diseases caused by viruses are a serious global health threat. Although the use of hand sanitizers containing alcohol and synthetic antiseptic agents is recognized as an effective, simple, and low-cost measure to combat viral transmission, they can harm human health and the environment. Thus, this work aimed to study the efficacy of combining Camellia sinensis and Chamomilla recutita extracts in a skin- and eco-friendly leave-on hand sanitizer to prevent the spread of respiratory viruses. An oil-in-water emulsion containing C. recutita oily extract (5.0%), C. recutita glycolic extract (0.2%) and C. sinensis glycolic extract (5.0%) showed virucidal activity against HAdV-2 (respiratory virus) and two surrogate viruses of SARS-CoV-2 (HSV-1 and MVH-3), showing great potential to prevent the spread of respiratory viruses. These natural extracts combined are also promising to combat a broad spectrum of other viruses, in the form of antiseptic mouthwashes or throat sprays, surface disinfectants, and veterinary products, among others. Complementally, the developed hand sanitizer demonstrated efficacy against bacteria and fungus.

The effect of the COVID-19 pandemic on the incidence and resistance of Gram-negative bacilli and antimicrobial consumption in the intensive care units of a referral hospital in Buenos Aires.

BACKGROUND: There was a reported increase in the antimicrobial consumption in hospitals during the COVID-19 pandemic, accompanied by an increase in infections due to multidrug-resistant (MDR) bacteria. METHODS: This retrospective time series study from intensive care units in Buenos Aires examined changes in antibiotic consumption (defined daily doses/1000 patients/day), the incidence of Gram-negative bacilli (GNB) and the mechanism of resistance. Antibiotics were categorised into group 1 (agents against MDR GNB) and group 2 (agents against non-MDR infections). Bacteriological samples included respiratory samples and blood cultures. Periods were divided into pre-pandemic (July 2019 to March 2020) and pandemic (April 2020 to March 2022). Correlation coefficients (r) were analysed and the Mann-Whitney test was performed to compare both periods. RESULTS: During the study period, GNB incidence, group 1 antibiotic consumption and resistance mechanisms increased, whereas antibiotics decreased in group 2. A significant positive correlation was seen between the consumption of antibiotics in group 1 and the incidence of GNB (r = 0.63; P < 0.001) and resistance (r = 0.52; P = 0.002). Significant differences were found between pre-pandemic and pandemic periods regarding the medians of group 1 consumption (520 [408-570] vs. 753 [495-851] DDD/1000 patients/day; P = 0.029), incidence of GNB (12 [10-13] vs. 43 [25-52.5] cases/month; P < 0.001) and resistance mechanisms (5 [4-8] vs. 17 [10-25] cases/month; P < 0.001), extended-spectrum beta lactamases (2 [1-2] vs. 6 [3-8] cases/month; P < 0.001) and metallo-beta-lactamases (0 [0-0] vs. 6 [1.75-8.5] cases/month; P < 0.001). CONCLUSION: During the COVID-19 pandemic, the rise in GNB incidence and the amount of resistance mechanisms significantly correlated with the increase in consumption of agents against MDR strains.

Challenges in Treating Pediatric Cancer Patients during the COVID-19 Pandemic: Balancing Risks and Care.

The COVID-19 pandemic has resulted in millions of fatalities worldwide. The case of pediatric cancer patients stands out since, despite being considered a population at risk, few studies have been carried out concerning symptom detection or the description of the mechanisms capable of modifying the course of the COVID-19 disease, such as the interaction and response between the virus and the treatment given to cancer patients. By synthesizing existing studies, this paper aims to expose the treatment challenges for pediatric patients with COVID-19 in an oncology context. Additionally, this updated review includes studies that utilized the antiviral agents Remdesivir and PaxlovidTM in pediatric cancer patients. There is no specific treatment designed exclusively for pediatric cancer patients dealing with COVID-19, and it is advisable to avoid self-medication to prevent potential side effects. Managing COVID-19 in pediatric cancer patients is indeed a substantial challenge. New strategies, such as chemotherapy application rooms, have been implemented for children with cancer who were positive for COVID-19 but asymptomatic since the risk of disease progression is greater than the risk of complications from SARS-CoV-2.

Synthesis, In Silico Study, and In Vitro Antifungal Activity of New 5-(1,3-Diphenyl-1H-Pyrazol-4-yl)-4-Tosyl-4,5-Dihydrooxazoles.

The increase in multi-drug resistant Candida strains has caused a sharp rise in life-threatening fungal infections in immunosuppressed patients, including those with SARS-CoV-2. Novel antifungal drugs are needed to combat multi-drug-resistant yeasts. This study aimed to synthesize a new series of 2-oxazolines and evaluate the ligands in vitro for the inhibition of six Candida species and in silico for affinity to the CYP51 enzymes (obtained with molecular modeling and protein homology) of the same species. The 5-(1,3-diphenyl-1H-pyrazol-4-yl)-4-tosyl-4,5-dihydrooxazoles 6a-j were synthesized using the Van Leusen reaction between 1,3-diphenyl-4-formylpyrazoles 4a-j and TosMIC 5 in the presence of K2CO3 or KOH without heating, resulting in short reaction times, high compound purity, and high yields. The docking studies revealed good affinity for the active site of the CYP51 enzymes of the Candida species in the following order: 6a-j > 4a-j > fluconazole (the reference drug). The in vitro testing of the compounds against the Candida species showed lower MIC values for 6a-j than 4a-j, and for 4a-j than fluconazole, thus correlating well with the in silico findings. According to growth rescue assays, 6a-j and 4a-j (like fluconazole) inhibit ergosterol synthesis. The in silico toxicity assessment evidenced the safety of compounds 6a-j, which merit further research as possible antifungal drugs.

Antiviral, anti-inflammatory and antioxidant effects of curcumin and curcuminoids in SH-SY5Y cells infected by SARS-CoV-2.

COVID-19, caused by SARS-CoV-2, affects neuronal cells, causing several symptoms such as memory loss, anosmia and brain inflammation. Curcuminoids (Me08 e Me23) and curcumin (CUR) are derived from Curcuma Longa extract (EXT). Many therapeutic actions have been linked to these compounds, including antiviral action. Given the severe implications of COVID-19, especially within the central nervous system, our study aims to shed light on the therapeutic potential of curcuminoids against SARS-CoV-2 infection, particularly in neuronal cells. Here, we investigated the effects of CUR, EXT, Me08 and Me23 in human neuroblastoma SH-SY5Y. We observed that Me23 significantly decreased the expression of plasma membrane-associated transmembrane protease serine 2 (TMPRSS2) and TMPRSS11D, consequently mitigating the elevated ROS levels induced by SARS-CoV-2. Furthermore, Me23 exhibited antioxidative properties by increasing NRF2 gene expression and restoring NQO1 activity following SARS-CoV-2 infection. Both Me08 and Me23 effectively reduced SARS-CoV-2 replication in SH-SY5Y cells overexpressing ACE2 (SH-ACE2). Additionally, all of these compounds demonstrated the ability to decrease proinflammatory cytokines such as IL-6, TNF-α, and IL-17, while Me08 specifically reduced INF-γ levels. Our findings suggest that curcuminoid Me23 could serve as a potential agent for mitigating the impact of COVID-19, particularly within the context of central nervous system involvement.

Macrolide resistance among Streptococcus agalactiae during COVID-19 public health emergency in Brazil.

During COVID-19 public health emergence, azithromycin was excessively used in Brazil, as part of a controversial "early treatment", recommended by former national health authorities. Excessive usage of macrolides may increase resistance rates among beta-hemolytic streptococci. Therefore, this study aimed to investigate the occurrence of resistance to erythromycin and clindamycin among Streptococcus agalactiae recovered from February 2020 to May 2023. Bacterial isolates (n = 116) were obtained from pregnant women and submitted to antimicrobial susceptibility testing, investigation of macrolide resistance phenotypes and genotypes, and identification of capsular type. The overall rate of erythromycin not susceptible (NS) isolates was 25.9%, while resistance to clindamycin was 5.2%. Drug efflux, associated with the M phenotype and mef(A) gene, was the prevalent mechanism of resistance (80%). Capsular type Ia was predominant (39.8%), followed by II, III, and V (17.7% each). A higher diversity of types was observed in the last years of the study. Type IV has had an increasing trend over time, being the fourth most common in 2023. The majority of the isolates that expressed the M phenotype presented capsular type Ia, while those with iMLS phenotype presented capsular type V. Despite no causal relationship can be established, azithromycin excessive usage may be a possible factor associated with this higher rate of erythromycin NS isolates, compared with most previous national studies. On the other hand, resistance to clindamycin has not changed significantly. Therefore, in the studied clinical setting, clindamycin remains a useful alternative to intrapartum prophylaxis among penicillin-allergic pregnant women.

Tocilizumab demonstrates superiority in decreasing C-reactive protein levels in hospitalized COVID-19 patients, compared to standard care treatment alone.

Severe acute respiratory syndrome coronavirus 2 has caused a global pandemic, leading to health, economic, and political crisis. The virus triggers the activation of inflammatory reactants including interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP), causing multiorgan damage, particularly affecting the lungs. Tocilizumab, an IL-6 receptor blocker, has the potential to diminish the progression of the disease and reduce organ damage and long-term complications. The aim of this observational retrospective cohort study was to evaluate the efficacy of tocilizumab in decreasing CRP levels in hospitalized coronavirus disease 2019 (COVID-19) patients compared to standard care without the drug. The study included 141 patients during their Hospital Stay (HS), with 100 in the Tocilizumab group and 41 in the non-Tocilizumab group. Clinical information was collected from the electronic clinical record, analyzed using statistical software, and homogenized the CRP levels from the severe group to the levels of the less complicated group at 48 h of hospitalization. The results showed a statistically significant greater decrease in CRP levels in the Tocilizumab group at 48 h after the use of the treatment, with no differences in mortality or length of stay between the groups. In conclusion, tocilizumab accelerates the diminishing of CRP levels compared to standard treatment alone, and its use may have potential benefits in the management of severe COVID-19 patients when used alongside with follow-up quantification of CRP levels reduction.IMPORTANCESevere acute respiratory syndrome coronavirus 2 has caused a global pandemic, leading to health, economic, and political crises. International guidelines for managing coronavirus disease 2019 (COVID-19) give recommendations according to the severity of the disease and the level of oxygen therapy needed. Tocilizumab is an option for the therapeutic management of hospitalized patients with any level of oxygen therapy; IL-6 serum level is the parameter for the follow-up on the efficacy, but it is not available at many hospitals. In this study, we demonstrate that C-reactive protein determination can predict the response to tocilizumab in severe COVID-19, the target patients for treatment with this drug. The use of this affordable and extensively available biomarker supports clinical decisions for the early escalation of the therapy and for the rational use of this drug on those prone to improve with the use of it.

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.

Pharmacodynamic of Recombinant Human Interferon Alpha-2b Nasal Drops and Effective Prophylaxis Against SARS-COV-2 Infection.

The recombinant human interferon alpha-2b (IFN-α2b) nasal drop formulation (Nasalferon) was studied as prophylaxis for SARS-CoV-2. Healthy volunteers between 19 and 80 years of age received 0.5 million international units of IFN in one drop (0.05 mL ) in each nostril, twice a day, for 10 consecutive days. The nondetection of SARS-CoV-2 by real-time polymerase chain reaction was the primary outcome variable. Several IFN-α biomarkers, including intranasal gene expression and innate immune effector activity, were increased in participants who received intranasal IFN-α2b. The study included 2,930 international travelers and 5,728 persons who were their close contacts. The subjects were treated with Nasalferon in January 2021, and 9,162 untreated travelers were included as controls. COVID-19 rate in treated subjects was significantly lower than in untreated subjects (0.05% vs. 4.84%). The proportion of travelers with COVID-19 decreased from 60.9% to 2.2% between December 2020 and February 2021. Furthermore, 1,719 tourism workers also received Nasalferon, and no cases of SARS-CoV-2 infection were detected, whereas 39 COVID-19 cases (10.6%) were reported in 367 untreated subjects. The main adverse events associated with the use of intranasal IFN-α2b were nasal congestion, headache, and rhinorrhea. Our prophylactic health interventions study demonstrates that the daily administration of Nasalferon for 10 days decreases the risk of developing COVID-19 in healthy volunteers. [Figure: see text].

Emerging threat: Antimicrobial resistance proliferation during epidemics - A case study of the SARS-CoV-2 pandemic in South Brazil.

The escalating global concern of antimicrobial resistance poses a significant challenge to public health. This study delved into the occurrence of resistant bacteria and antimicrobial resistance genes in the waters and sediments of urban rivers and correlated this emergence and the heightened use of antimicrobials during the COVID-19 pandemic. Isolating 45 antimicrobial-resistant bacteria across 11 different species, the study identifies prevalent resistance patterns, with ceftriaxone resistance observed in 18 isolates and ciprofloxacin resistance observed in 13 isolates. The detection of extended-spectrum ß-lactamases, carbapenemases, and acquired quinolone resistance genes in all samples underscores the gravity of the situation. Comparison with a pre-pandemic study conducted in the same rivers in 2019 reveals the emergence of previously undetected new resistant species, and the noteworthy presence of new resistant species and alterations in resistance profiles among existing species. Notably, antimicrobial concentrations in rivers increased during the pandemic, contributing significantly to the scenario of antimicrobial resistance observed in these rivers. We underscore the substantial impact of heightened antimicrobial usage during epidemics, such as COVID-19, on resistance in urban rivers. It provides valuable insights into the complex dynamics of antimicrobial resistance in environmental settings and calls for comprehensive approaches to combat this pressing global health issue, safeguarding both public and environmental health.