Antiviral Therapy最新文献

Background: COVID-19 has become the center of attention since its outbreak in December 2019. Despite the discovery of its preventive vaccine, role of healthy immune system is undebatable. Functional foods are continuously hunted as a promising option for a safe natural therapeutic treatment.Purpose: This review demonstrates how functional foods can boost host immune system, promote antiviral operation, and synthesize biologically effective molecules against SARS-COV-2.Research Methodology: For current review, online search was conducted for nature-based functional immune boosters against SARS-COV-2.Conclusion: Functional foods, alongside a healthy lifestyle, fortifies the human immune system and could all help to dramatically lower the cost burden of COVID-19, the suffering of the patients, and the mortality rates worldwide.

Background: Integrase strand transfer inhibitors (INSTIs) have been associated with excess weight gain in people living with HIV compared to other antiretroviral agents. The mechanisms that underlie these effects are not well defined. Thus, we aimed to examine the effects of switching to INSTI-containing regimens on clinical metabolic parameters.

Setting: A secondary analysis of a prospective cohort study in which people living with HIV on a stable efavirenz-based regimen were switched to a cobicistat-boosted elvitegravir or raltegravir-containing regimen. Participants remained on the NRTI backbone of tenofovir disoproxil fumarate and emtricitabine.

Methods: Frozen plasma samples from 19 participants were used to determine concentrations of leptin, adiponectin, insulin and lactate at baseline and 8 weeks post-switch. Fasting lipids and blood glucose not reported in the initial study were obtained to examine metabolic changes. Anthropometric data including height and weight were abstracted from the medical record.

Results: Participants switched from efavirenz to cobicistat-boosted elvitegravir without change in tenofovir disoproxil fumarate/emtricitabine backbone showed a 20% increase in HOMA-IR after 8 weeks (1.84 vs 2.24, p < .05), due mostly to increases in fasting insulin. This increase occurred independent of weight gain in the cohort as whole (83.4 vs 85.9 kg, pre vs post, p = .04), but was linked to increases in circulating lactate.

Conclusions: Participants switched to an INSTI-based regimen tended to gain weight, and those switched to cobicistat-boosted elvitegravir had increases in markers of insulin resistance and elevation in plasma lactic acid compared to raltegravir, suggesting that elvitegravir may promote metabolic perturbations in people living with HIV.

Background: Nirmatrelvir has been shown to reduce morbidity and mortality associated with COVID-19. However, it is underutilized due to concerns regarding COVID-19 symptom rebound following nirmatrelvir's standard 5-day course. This study aims to identify and evaluate a nirmatrelvir dosage regimen that lowers symptom rebound.

Methods: Based on nirmatrelvir pharmacokinetics, we propose a novel 8-day regimen: two doses twice-daily followed by six doses once-daily to reduce rebound frequency. We then carried out a retrospective case series study of clinical outcomes among our patients to investigate their frequency of COVID-19 symptom rebound following nirmatrelvir usage.

Results: Among the 58 prescribed case patients, 49 filled and initiated the prescription. Of those 49 patients, four took the medication for fewer than 5 days, 24 for 5 days (standard regimen), and 21 for 7 or 8 days (extended regimen). Among 5-day treatment cases (n = 24), 8 (33%) experienced clinical rebound, whereas among the 7-day or 8-day treatment cases (n = 21), 2 (9.5%) experienced rebound.

Conclusions: These findings suggest that a longer nirmatrelvir/ritonavir course might reduce rebound symptoms compared to the standard 5-day regimen.

Background: The COVID-19 pandemic has created an urgent need for effective therapeutic agents. The SARS-CoV-2 Main Protease (M^pro) plays a crucial role in viral replication and immune evasion, making it a key target for drug development. While several studies have explored M^pro inhibition, identifying FDA-approved drugs with potential efficacy remains a critical research focus.

Purpose: This study aims to identify FDA-approved drugs that could inhibit SARS-CoV-2 M^pro. Using computational screening, we seek compounds that share structural similarities with a known co-crystallized ligand (PRD_002214) and exhibit strong binding affinity to the enzyme, providing viable candidates for COVID-19 treatment.

Research design: A systematic in silico approach was used, screening 3009 FDA-approved drugs. The initial screening focused on structural similarity to PRD_002214 (PDB ID: 6LU7), followed by molecular docking studies to predict binding affinity. Promising compounds were further analyzed through molecular dynamics (MD) simulations to evaluate their stability and interactions with M^pro over 100 ns.

Study sample: Of the 3009 FDA-approved drugs screened, 74 were selected for initial evaluation. After refinement, 28 compounds underwent docking analysis, with eight showing strong binding potential to M^pro.

Analysis: Molecular docking assessed the binding affinity and interaction of the selected compounds with M^pro. MD simulations were conducted on the top compound, Atazanavir, to study its dynamic interactions. MM-GBSA, PLIP, and PCAT analyses were used to validate binding affinity and interactions.

Results: Eight compounds, including Carfilzomib, Atazanavir, Darunavir, and others, exhibited promising binding affinities. Among them, Atazanavir showed the highest binding strength and was selected for further MD simulation studies. These simulations revealed that Atazanavir forms stable interactions with M^pro, demonstrating favorable binding and dynamic stability. The binding affinity was further confirmed through MM-GBSA, PLIP, and PCAT analyses, supporting Atazanavir's potential as an effective M^pro inhibitor.

Conclusions: In silico results suggest that Atazanavir is a promising candidate for targeting SARS-CoV-2 M^pro, with strong binding affinity and dynamic stability. These findings support its potential as a lead compound for further preclinical and clinical testing, though in vitro and in vivo validation are needed to confirm its therapeutic efficacy against COVID-19.

Introduction: BIC/FTC/TAF showed efficacy and tolerability in randomized trials as a switch strategy in virologically-suppressed people living with HIV. We evaluated its effectiveness in a real-life setting.

Methods: A retrospective monocentric cohort including 431 virologically-suppressed (HIV-RNA <50 copies/ml) people switching to BIC/FTC/TAF in the period 2018-2022 was evaluated. Probabilities of virological failure (VF, i.e.2 consecutive HIV-RNA ≥50 copies/ml or a single HIV-RNA ≥200 copies/ml) and of treatment discontinuation (TD) were estimated by Kaplan-Meier, and predictors of both outcomes were identified through multivariable Cox regression. Analysis-of-variance for repeated measures was used to examine changes in CD4 count and CD4-to-CD8 ratio.

Results: Overall, 16 VF occurred during 22 months of median follow-up time. Estimated probabilities of VF at 1, 2 and 3 years were 2.0% (95% CI 1.04.2%), 2.9% (95% CI 1.5%-5.6%) and 5.5% (95% CI 3.2%-9.2%), respectively. Caucasian ethnicity and a history of previous VF independently predicted VF. TD occurred in 42 cases, predominantly for simplification. One discontinuation due to VF was reported. No predictors of discontinuation were identified. An increase in CD4-to-CD8 ratio over 3 years was evidenced (p < 0.001). Total cholesterol decreased over 3 years (p < 0.001). Triglycerides did not significantly change (p = 0.465).

Conclusions: BIC/FTC/TAF demonstrated high effectiveness, tolerability and safety.

Introduction: This study aimed to analyze the risk factors for varicella encephalitis in children and establish a predictive model.

Methods: This retrospective cohort study included a varicella encephalitis group (n = 75) and a varicella-non-encephalitis group (n = 135). Logistic regression analysis was employed to find risk factors for varicella encephalitis and create a predictive model.

Results: Older age, vomiting, poor mental status, and prolonged rash duration were independent risk factors for varicella encephalitis (p < .05). The predictive model for varicella encephalitis combined above four factors. The ROC curve of the predictive model showed an area under the curve of 0.955 (95% CI 0.925-0.986) for varicella encephalitis in children with a sensitivity of 94.7%, and a specificity of 86.0%.

Conclusion: Children with varicella who are older, experience vomiting, exhibit poor mental status, or have a prolonged rash duration should be closely monitored clinically. The predictive model combining these four factors demonstrates good predictive efficiency.

Angiotensin-converting enzyme 2 (ACE2) is the receptor that enables SARS-CoV-2 to invade host cells. Previous studies have reported that reducing ACE2 expression may have an anti-SARS-CoV-2 effect. In this study, we constructed a pGL4.10-F2-ACE2 vector with double luciferase genes (firefly and Renilla luciferase) under the control of the ACE2 promoter and used it to screen compounds from Chinese traditional medicinal herbs (CTMHs) that can inhibit ACE2 transcription in human cells. We transfected HEK293T cells with pGL4.10-F2-ACE2 and treated them with CTMH compounds and then measured fluorescence to evaluate the indirect inhibition of ACE2 transcription. Out of 37 compounds tested, andrographolide demonstrated a dose-dependent inhibition of ACE2 transcription. We further confirmed by RT-qPCR and Western blot assays that andrographolide also reduced ACE2 expression in BEAS-2B cells in a dose-dependent manner. Moreover, pseudovirus infection assays in BEAS-2B cells demonstrated that andrographolide can inhibit SARS-CoV-2 infection in a dose-dependent manner. These results suggest that andrographolide has potential anti-SARS-CoV-2 activity and could be a candidate drug for COVID-19 prevention and treatment.

Background: Monkeypox has emerged as a noteworthy worldwide issue due to its daily escalating case count. This illness presents diverse symptoms, including skin manifestations, which have the potential to spread through contact. The transmission of this infectious agent is intricate and readily transfers between individuals.Methods: The hypothetical protein MPXV-SI-2022V502225_00135 strain of monkeypox underwent structural and functional analysis using NCBI-CD Search, Pfam, and InterProScan. Quality assessment utilized PROCHECK, QMEAN, Verify3D, and ERRAT, followed by protein-ligand docking, visualization, and a 100-nanosecond simulation on Schrodinger Maestro.Results: Different physicochemical properties were estimated, indicating a stable molecular weight (49147.14) and theoretical pI (5.62) with functional annotation tools predicting the target protein to contain the domain of Chordopox_A20R domain. In secondary structure analysis, the helix coil was found to be predominant. The three-dimensional (3D) structure of the protein was obtained using a template protein (PDB ID: 6zyc.1), which became more stable after YASARA energy minimization and was validated by quality assessment tools like PROCHECK, QMEAN, Verify3D, and ERRAT. Protein-ligand docking was conducted using PyRx 9.0 software to examine the binding and interactions between a ligand and a hypothetical protein, focusing on various amino acids. The model structure, active site, and binding site were visualized using the CASTp server, FTsite, and PyMOL. A 100 nanosecond simulation was performed with ligand CID_16124688 to evaluate the efficiency of this protein.Conclusion: The analysis revealed significant binding interactions and enhanced stability, aiding in drug or vaccine design for effective antiviral treatment and patient management.

Background: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) was developed as a once-daily, complete antiretroviral (ARV) regimen therapy to address the need for simplified protease inhibitor-based ARV regimens. This study assessed the swallowability and acceptability for long-term use of scored placebo tablets matching the D/C/F/TAF FDC tablets in children living with HIV-1.

Methods: This study (NCT04006704) was a Phase 1, open-label, randomized, single-dose, 2-period, 2-sequence crossover study in children living with HIV-1, aged ≥6 to <12 years and weighing ≥25 to <40 kg, on a stable ARV regimen for ≥3 months. Participants were asked to swallow whole (size, 21 × 11 × 7 mm) and split matching placebo D/C/F/TAF tablets. Swallowability of the matching placebo D/C/F/TAF tablets (primary endpoint) was assessed by observers. Acceptability of taking matching placebo D/C/F/TAF tablets and current ARVs was evaluated by participants using a 3-point questionnaire. Participants rated the acceptability for long-term daily use of the placebo D/C/F/TAF tablets, and observers assessed how easily caregivers could split a scored tablet by hand, using 3-point questionnaires.

Results: Among the 24 participants who enrolled and completed the study, 95.8% (23/24) were able to swallow the whole and split matching placebo D/C/F/TAF tablets after 1 or 2 attempts. Most participants (>70%) rated the acceptability of tablets for long-term daily use as acceptable or good to take. Breaking the tablets was considered easy or OK by 79.2% (19/24) of caregivers.

Conclusion: Scored D/C/F/TAF FDC tablets are swallowable - with whole favoured over split - and considered at least acceptable for long-term daily intake in children living with HIV-1 aged ≥6 to <12 years.

Trial registration: ClinicalTrials.gov Identifier: NCT04006704.