Comparative efficacy and safety of tenofovir amibufenamide vs tenofovir alafenamide in the initial 48-week treatment of high viral load chronic hepatitis B: A single-centre retrospective study
Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB).
Antiviral potential of phenolic compounds against HSV-1: In-vitro study
This in vitro study aimed to investigate the effect of several phenolic compounds, including doxorubicin, quercetin, and resveratrol, on HSV-1 infection.
Analysis of risk factors and prediction model construction for varicella encephalitis in children: A retrospective cohort study
This study aimed to analyze the risk factors for varicella encephalitis in children and establish a predictive model.
Clinical outcomes in patients with mild to moderate coronavirus disease 2019 treated with monoclonal antibody therapy versus an untreated control cohort
Monoclonal antibody therapy (MAT) received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for mild to moderate COVID-19 treatment in adults at a high-risk for progression to severe disease in November 2020. This study assessed the impact of MAT on clinical outcomes.
approach to characterize the structure and function of a hypothetical protein of Monkeypox virus exploring Chordopox-A20R domain-containing protein activity
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. 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. 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: ), 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. The analysis revealed significant binding interactions and enhanced stability, aiding in drug or vaccine design for effective antiviral treatment and patient management.
Andrographolide suppresses SARS-CoV-2 infection by downregulating ACE2 expression: A mechanistic study
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.
Assessment of swallowability and acceptability of scored darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) tablets in HIV-1-infected children aged ≥6 to <12 years, using matching placebo tablets: A randomized study
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.
Failure of bamlanivimab with selection of E484K mutation in an allogeneic stem cell transplant recipient with nosocomial SARS-CoV-2 infection
We report the case of an allogeneic stem cell transplant recipient with nosocomial acquisition of SARS-CoV-2 infection who received antispike neutralizing monoclonal antibody bamlanivimab 2 days after diagnosis of SARS-CoV-2 infection but progressed to severe COVID-19 pneumonia and died with the selection of E484K/Q resistance mutations to bamlanivimab.
Adverse drug reactions attributed to generic substitution of antiretroviral medications among HIV treatment and pre-exposure prophylaxis clients in British Columbia, Canada
In British Columbia, antiretrovirals (ARVs) for HIV treatment (HIV-Tx) and pre-exposure prophylaxis (PrEP) are free-of-charge through publicly-funded Drug Treatment Programs (DTPs). When available, less costly generics are substituted for brand-name ARVs. We describe the incidence and type of product substitution issue (PSI) adverse drug reactions (ADRs) attributed to generic ARVs.
RVX-208, an inducer of Apolipoprotein A-I, inhibits the particle production of hepatitis B virus through activation of cGAS-STING pathway
Previously, we have demonstrated that Apolipoprotein A-I (ApoA-I) could inhibit the secretion of Hepatitis B virus (HBV), suggesting that stimulation of ApoA-I may block particle production. In the present study, we evaluated the anti-HBV effect of RVX-208, a small-molecule stimulator of ApoA-I gene expression.
Cross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA
Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function for the treatment of heavily treatment-experienced people with HIV (PWH) harbouring multidrug resistance in combination with an optimized background regimen (OBR). Here, we describe in vitro analysis of the interplay between entry inhibitors (EI; enfuvirtide, fostemsavir, ibalizumab, and maraviroc) susceptibility and LEN susceptibility in samples from 72 participants in the phase 2/3 CAPELLA study, as well as the emergence of resistance in CAPELLA through 52 weeks.
Waitlist-controlled trial of an online intervention to address mental health among older people living with HIV
Older people living with HIV (PLWH) often experience elevated levels of depression, anxiety, and loneliness. This waitlist-controlled trial examined the effectiveness of online audio mindfulness lessons in impacting these feelings among older PLWH. Among 214 participants, the mean (SD) age was 60.4 (5.9) years, 89% were male, and 69% were white. After 25 days, the intervention group showed significant improvements versus the waitlist control group in symptoms of depression (20.3% improvement, < .01) and symptoms of anxiety (22.4% improvement, = .03), but not in loneliness as measured by a Daily Diary (12.9% improvement, = .07) or the 3-Item Loneliness Scale (4.8% improvement, = .27). Secondary analyses among participants with elevated baseline symptoms of depression showed a 26.3% improvement ( < .01), with a moderate effect size (Hedge's g = 0.69). Similarly, those with elevated baseline symptoms of anxiety showed a 25.6% improvement ( < .01), a moderate effect size (g = 0.54), while those with moderate or severely elevated loneliness showed an 18.9% improvement in daily loneliness ( < .01), a moderate effect size (g = 0.55). This waitlist-controlled trial is the first to show that a series of brief, online audio mindfulness lessons improves mental health outcomes among older PLWH. For many patients, this intervention may offer relief that is both accessible and affordable.
Dolutegravir and rilpivirine as successful initial antiretroviral therapy in a treatment-naive patient with HIV-1: A case report
Retrospective chart review of transplant recipients with cytomegalovirus infection who received maribavir in the Phase 3 SOLSTICE trial: Data at 52 weeks post-maribavir treatment initiation
Cytomegalovirus (CMV) infection is a frequent complication in haematopoietic cell/solid organ transplant (HCT/SOT) recipients. Previous studies report all-cause mortality rates of 31% and 50% in HCT/SOT recipients post-treatment initiation with conventional anti-CMV therapies for refractory or resistant CMV.
Computer-assisted drug discovery of potential natural inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase through a multi-phase approach
The COVID-19 pandemic has led to significant loss of life and economic disruption worldwide. Currently, there are limited effective treatments available for this disease. SARS-CoV-2 RNA-dependent RNA polymerase (SARS-CoV-2 RdRp) has been identified as a potential target for drug development against COVID-19. Natural products have been shown to possess antiviral properties, making them a promising source for developing drugs against SARS-CoV-2.
HIV drug resistance in the era of contemporary antiretroviral therapy: A clinical perspective
Contemporary antiretroviral therapy (ART) regimens have high barriers to the development of drug resistance. However, resistance to earlier antiretrovirals and uncommon cases of resistance to contemporary ART illustrate the continued need for good clinical management of HIV drug resistance. Here, we describe HIV drug-resistance mechanisms, the interaction of HIV drug-resistant mutations and the patterns of drug resistance to contemporary ART. We then provide guidance on the management of HIV drug resistance, including how to limit the development of resistance and manage virologic failure that is complicated by resistance. To complement this, links to resources and treatment guidelines are provided that can assist with the interpretation of HIV drug resistance test results and optimal ART selection in the clinic.
Andrographolide inhibits infectious bronchitis virus-induced apoptosis, pyroptosis, and inflammation
Avian infectious bronchitis virus (IBV), a coronavirus, causes a huge economic loss to the poultry industry. Andrographolide (APL) is a compound with a variety of pharmacological properties, including antiviral and anti-inflammatory effects. In this study, APL was evaluated for antiviral activity by its anti-apoptotic, anti-pyroptosis, and anti-inflammatory effects.
Subacute thyroiditis following COVID-19 vaccination: Case presentation
Subacute thyroiditis (SAT) is an organ-specific disease that various drugs, including COVID-19 vaccines, can trigger. COVID-19 infection has been associated with thyroid gland damage and disease SARS-CoV-2 direct action, euthyroid sick syndrome, and immune-mediated mechanisms are all potential mechanisms of thyroid damage. It denotes thyroid gland inflammation, most commonly of viral origin, and belongs to the transitory, self-limiting thyroid gland diseases group, causing complications in approximately 15% of patients in the form of permanent hypothyroidism. Some authors say SAT is the most common thyroid disease associated with COVID-19. The occurrence of SAT many weeks after administering the second COVID-19 vaccine is rare and has limited documentation in academic literature. This study aims to present the occurrence of SAT after administering the COVID-19 vaccine. We present the case of a 37-year-old man who developed SAT 23 days after receiving the second dose of Pfizer BioNTech's COVID-19 mRNA vaccine. Due to neck pain and an elevated body temperature (up to 38.2°C), a 37-year-old male subject presented for examination 23 days after receiving the second Pfizer BioNTech mRNA vaccine against SARS-CoV-2 viral infection. The patient denied ever having an autoimmune disease or any other disease. Painful neck palpation and a firm, slightly enlarged thyroid gland with no surrounding lymphadenopathy were identified during the exam. The heart rate was 104 beats per minute. All of the remaining physical findings were normal. Data collected during the disease are integral to the medical record. Hematology and biochemistry analyses at the initial and follow-up visits revealed minor leukocytosis, normocytic anaemia, and thrombocytosis, followed by a mild increase in lactate dehydrogenase and decreased iron levels. The patient's thyroid function and morphology had recovered entirely from post-vaccine SAT.: Results from this study emphasise the need for healthcare professionals to promptly report any case of SAT related to COVID-19 vaccination. Further investigation is warranted to understand the immunopathogenesis of COVID-19-associated thyroiditis and the impact of COVID-19 immunization on this condition.
Hepatitis C virus/Hepatitis B virus coinfection: Current prospectives
In endemic areas, hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection is common, and patients with coinfection have a higher risk of developing liver disease such as hepatocellular carcinoma, liver fibrosis and cirrhosis. In such cases, HCV predominates, and HBV replication is suppressed by HCV. HCV core proteins and interferons that are activated by HCV are responsible for the suppression of HBV. Immunosuppression is also seen in patients with HCV and HBV coinfections. A decrease in HCV-neutralizing antibody response and circulation of Th1-like Tfh cells is observed in patients with HCV and HBV coinfection. Both viruses interacted in the liver, and treatment of HCV/HBV coinfection is genotype-based and complex due to the interaction of both viruses. In HCV-dominant cases, direct-acting antiviral drugs and peg interferon plus ribavirin are used for the treatment, with continuous monitoring of AST and ALT. HBV-dominant cases are less common and are treated with peg interferon and nucleoside nucleotide analogues with monitoring of AST and ALT. The SVR rate in HCV-HBV coinfection is higher than that in monoinfection when treated with direct-acting antiviral drugs. But there is a risk of reactivation of HBV during and after therapy. The rate of reactivation is lower in patients treated with direct-acting antiviral drugs as compared to those treated with peg interferon plus ribavirin. Biomarkers of HBV such as HBcrAg, HBV DNA and HBVpg RNA are not effective in the prediction of HBV reactivation; only the hepatitis B surface antigen titre can be used as a biomarker for HBV reactivation. HCV can also be reactive, but this is found in very rare cases in which HBV is present and is treated first.
Fanconi syndrome, diabetes insipidus, and acute kidney injury due to tenofovir disoproxil fumarate: A case report
Tenofovir disoproxil fumarate is widely used in Botswana as part of the first-line antiretroviral regimen in the 'Treat All' strategy implemented in 2016 by the Ministry of Health. Its use has been associated with several uncommon adverse renal effects, though rarely all in conjunction or without the combined use of protease inhibitors.
Letter to the editor on use of antibodies from convalescent sera in the treatment of moderate and severe Covid-19 infection