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Chrysanthemum stunt viroid (CSVd) telah banyak dilaporkan menjadi salah satu faktor pembatas dalam usaha produksi bunga potong krisan. Penelitian bertujuan untuk mengetahui pengaruh perlakuan suhu rendah (5 ℃) dan antiviral ribavirin terhadap pertumbuhan dan pembebasan CSVd pada planlet krisan yang dikultur dari ujung tunas. Tanaman terinfeksi CSVd diperoleh dari kebun percobaan milik pemerintah di Cianjur, Jawa Barat. Penelitian dilakukan dengan beberapa tahap, yaitu 1) pengambilan sampel tanaman, 2) deteksi viroid dengan metode RT-PCR, 3) inisiasi eksplan dan perbanyakkan bahan tanaman secara in vitro, 4) perlakuan suhu rendah 5 ℃ dengan tiga taraf waktu inkubasi (1, 3, dan 5 bulan), 5) perlakuan antiviral ribavirin dengan tiga taraf konsentrasi (25, 100, dan 125 ppm), dan 6) konfirmasi bahan tanaman bebas viroid dengan RT-PCR. Hasil penelitian menunjukkan bahwa penyimpanan suhu rendah dan perlakuan ribavirin menurunkan laju pertambahan tinggi tunas dan jumlah daun. Sampai pada konsentrasi 125 ppm, walaupun menurunkan laju pertumbuhan tunas dan jumlah daun, ribavirin tidak menimbulkan toksisitas terhadap tanaman. Akan tetapi, kombinasi perlakuan suhu rendah (1, 3, dan 5 bulan) dengan ribavirin (25, 100, dan 125 ppm) belum mampu mengeliminasi CSVd dari jaringan pada semua taraf perlakuan.

Background: Oxidative stress and its end products, such as malondialdehyde (MDA) play a leading role in the pathogenesis of hepatitis C. Melatonin is a hormone that helps regulate circadian rhythms, which likely play a role in infectious diseases in terms of susceptibility, clinical expression, and outcome. Objective: The present study was conducted to assess serum malondialdehyde and melatonin levels in patients with chronic hepatitis C infection before and after the intake of direct-acting antivirals. Method: Forty hepatitis C patients were the subjects of this study. While ten healthy volunteers who matched in age and socioeconomic status served as the control subjects. Malondialdehyde and melatonin were assayed in the serum of the three groups, and the results were statistically analyzed. Results: Hepatitis C patients had significantly higher malondialdehyde (p < 0.001) but significantly lower melatonin (p < 0.001) as compared to the healthy controls. After 12 weeks of treatment with direct-acting antivirals, the malondialdehyde level decreased significantly (p < 0.001) and the melatonin level increased significantly (p < 0.001). A significant negative correlation between malondialdehyde and melatonin was observed. Conclusion: The present findings suggest that treatment of hepatitis C patients with Direct-acting antivirals improves liver function parameters and antioxidant profiles. [ABSTRACT FROM AUTHOR]

2014, 58: 3636 20 Zhang, N. Zhang, S. Szostak, J W. J. Am. Chem. Soc. 2012, 134: 3691 21 Kim, S C. Zhou, L. Zhang, W. O'Flaherty, D K. Rondo-Brovetto, V. Szostak, J W. J. Am. Chem. Soc. 2020, 142: 2317 22 Guschlbauer, W. Jankowski, K. Nucleic Acids Res. 1980, 8: 1421 23 Plavec, J. Tong, W. Chattopadhyaya, J. J. Am. Chem. Soc. 1993, 115: 9734 24 Prakash, T P. Chem. Biodivers. Keywords: nucleosides; hepatitis C; prodrugs; antiviral agents; protides; density functional theory EN nucleosides hepatitis C prodrugs antiviral agents protides density functional theory 1607 1615 9 07/31/23 20230815 NES 230815 Graph Nucleosides and nucleotides have long been recognized as privileged chemical structures due to their integral role in life as the monomers of nucleic acids. Synthesis and Antiviral Evaluation of 2',3'- - C -Disubstituted Nucleoside Analogue ProTides to Test a Conformational Model of Potency Against Hepatitis C See: Ashby, E C. Parris, G E. J. Am. Chem. Soc. 1971, 93: 1206 63 Hugelshofer, C L. Palani, V. Sarpong, R. J. Am. Chem. Soc. 2019, 141: 8431 64 Krasovskiy, A. Kopp, F. Knochel, P. Angew. [Extracted from the article]

A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the analysis of ribavirin in chicken. Samples was extracted with 0.1% formic acid and purified by Hypercarb cartridge prior to LC–MS/MS analysis. The eluates were evaporated to dryness, reconstituted in 1 mL 5mM ammonium acetate containing 5% acetonitrile (v/v) and 0.1% (v/v) formic acid. Chromatographic separation was performed on a Hypercarb analytical column under a gradient elution program with acetonitrile and 0.1% (v/v) formic acid in 5 mM ammonium acetate at a flow rate of 0.6 ml/min. The intraday and interday accuracy ranged from − 7.83 − 1.39%, and − 6.38 − 2.25%, with precisions between 1.34 − 3.88%% and 1.10 − 4.67%. The limits of detection (LODs) and limits of quantitation (LOQs) of ribavirin was 0.1 ng/mL and 0.5 ng/mL, respectively. The method was validated for linearity, accuracy, precision, matrix effect and stability. Application of the method confirmed 3 ribavirin positive samples out of 50 commercial chicken samples, with concentrations of ribavirin ranging from 0.9 μg/kg to 5.8 μg/kg a, respectively. Additionally, both AB Sciex 5500 and Agilent 6945B were proven to be suitable in ribavirin separation and quantification. The described method is suitable for the determination of ribavirin in chicken in analytical practice to monitor illegal addition of this kind of anti–viral drug. [ABSTRACT FROM AUTHOR]

The introduction of direct‐acting antiviral (DAA) treatment of hepatitis C virus (HCV) infected patients has greatly increased treatment success rates. However, viral response kinetics to DAA treatment may depend on pre‐existing resistance‐associated substitutions (RASs) in HCV. The aim of this study was to describe how pre‐existing RASs affect DAA treatment‐induced reduction in HCV RNA titers in HCV genotypes 1‐ and 3‐infected individuals. Patients with HCV genotype 1 infection (N = 31) treated with either sofosbuvir/ledipasvir/ribavirin or paritaprevir/ombitasvir/ritonavir/dasabuvir/ribavirin and HCV genotype 3‐infected patients (N = 16) treated with either sofosbuvir/daclatasvir/ribavirin or sofosbuvir/ribavirin were analyzed. HCV RNA levels were determined at baseline and frequently during treatment, and RAS profiles were obtained by deep sequencing at baseline. In total, 33/47 (70.2%) of the patients had baseline RASs. However, treatment‐specific RASs were detected at baseline only in 12.9% and 18.8% of HCV genotypes 1‐ and 3‐infected patients, respectively. In genotype 1‐infected individuals, reduction in HCV RNA titer during the first week of treatment was not affected by evidence of either treatment‐specific RASs or cirrhosis or treatment regimen. In genotype 3‐infected individuals receiving sofosbuvir/daclatasvir/ribavirin, the presence of daclatasvir‐specific NS5A RASs at baseline correlated with a reduced decline of HCV RNA in the first treatment week. For both genotypes 1‐ and 3‐infected individuals, cirrhosis but not treatment‐specific RAS were associated with the time of clearance of HCV RNA. It is, however, important to note that this study involves DAA regimens that were used only during the original introduction of interferon‐free DAA‐based treatments. [ABSTRACT FROM AUTHOR]

Apple hammerhead viroid (AHVd) was detected in the apple cultivar 'Šampion' and in mixed infection with Solanum nigrum ilarvirus 1 (SnIV-1) in the cultivars 'Selena' and 'Jonagored Supra', using a high-throughput sequencing method. Experiments were conducted to eliminate both pathogens in apples using meristem tip cultures in combination with the antivirotics ribavirin, rimantadine, and zidovudine. Elimination of both pathogens was verified by repeated RT-PCR and qRT-PCR assays after 7–11 months. Elimination of SnIV-1 from all cultivars was successful with each of the three antivirotics at concentrations of 20, 40, and 80 mg L−1. Elimination of AHVd was also achieved, although less effectively and only with ribavirin in the concentration range of 20–160 mg L−1. [ABSTRACT FROM AUTHOR]

The human respiratory syncytial virus (hRSV) is a major cause of serious lower respiratory infections and poses a considerable risk to public health globally. Only a few treatments are currently used to treat RSV infections, and there is no RSV vaccination. Therefore, the need for clinically applicable, affordable, and safe RSV prevention and treatment solutions is urgent. In this study, an ion-activated in situ gelling formulation containing the broad-spectrum antiviral 18β-glycyrrhetinic acid (GA) was developed for its antiviral effect on RSV. In this context, pH, mechanical characteristics, ex vivo mucoadhesive strength, in vitro drug release pattern, sprayability, drug content, and stability were all examined. Rheological characteristics were also tested using in vitro gelation capacity and rheological synergism tests. Finally, the cytotoxic and antiviral activities of the optimized in situ gelling formulation on RSV cultured in the human laryngeal epidermoid carcinoma (HEp-2) cell line were evaluated. In conclusion, the optimized formulation prepared with a combination of 0.5% w/w gellan gum and 0.5% w/w sodium carboxymethylcellulose demonstrated good gelation capacity and sprayability (weight deviation between the first day of the experiment (T0) and the last day of the experiment (T14) was 0.34%), desired rheological synergism (mucoadhesive force (Fb): 9.53 Pa), mechanical characteristics (adhesiveness: 0.300 ± 0.05 mJ), ex vivo bioadhesion force (19.67 ± 1.90 g), drug content uniformity (RSD%: 0.494), and sustained drug release over a period of 6 h (24.56% ± 0.49). The optimized formulation demonstrated strong anti-hRSV activity (simultaneous half maximal effective concentration (EC50) = 0.05 µg/mL; selectivity index (SI) = 306; pre-infection EC50 = 0.154 µg/mL; SI = 100), which was significantly higher than that of ribavirin (EC50 = 4.189 µg/mL; SI = 28) used as a positive control against hRSV, according to the results of the antiviral activity test. In conclusion, this study showed that nasal in situ gelling spray can prevent viral infection and replication by directly inhibiting viral entry or modulating viral replication. [ABSTRACT FROM AUTHOR]

The combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is recommended for the retreatment of patients with HCV infection in whom previous direct-acting antiviral (DAA) treatment failed. However, whether ribavirin further increases the therapeutic efficacy of SOF/VEL/VOX retreatment remains unclear. We aimed to test this hypothesis in a randomized-controlled trial. We randomly assigned 315 patients with DAA treatment failure from five Egyptian sites into two groups. Group A (n = 158) received SOF/VEL/VOX for 12 weeks, and group B (n = 157) received SOF/VEL/VOX + weight-based ribavirin for 12 weeks. Therapeutic efficacy was defined as SVR12 (sustained virologic response 12 weeks after treatment end). Safety and tolerability were evaluated by monitoring treatment-related adverse events (AEs) and laboratory abnormalities. Males comprised 53.9% of group A and 57.1% of group B (p = 0.58); mean ages were 51.8 and 47.3 years in group A and B, respectively. Seventeen patients in each group were lost to follow-up. SVR12 rates were 87.3% (138/158) by intention-to-treat analysis and 97.8% (138/141) by per-protocol analysis in group A; and 87.9% (138/157) and 98.5% (138/140), respectively, in group B (p = n.s. for intention-to-treat and per-protocol analyses). Both regimens were well-tolerated, with no deaths and only one serious AE (anemia) in group B, which required ribavirin discontinuation. Fifty-five patients in group A vs. 77 in group B experienced any AE (p = 0.002). This randomized-controlled trial showed equal, high efficacy of both regimens for the retreatment of previous DAA failures, although ribavirin was associated with more AEs. Therefore SOF/VEL/VOX monotherapy should be the preferred retreatment strategy. NCT04695769. HCV treatment guidelines recommend retreatment of direct-acting antiviral (DAA) treatment failures with the combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) for 12 weeks. However, whether ribavirin exerts an additional/synergistic effect remains unclear. The present study confirmed that SOF/VEL/VOX without ribavirin is the best regimen for retreatment of DAA treatment failures, and thus will help guide clinicians caring for patients who are not cured with a first course of DAA therapy. [Display omitted] • Whether ribavirin improves the efficacy of SOF/VEL/VOX in HCV retreatment is unclear. • Ribavirin did not increase the cure rate compared to SOF/VEL/VOX monotherapy but led to more adverse events. • SOF/VEL/VOX monotherapy is the preferred retreatment strategy for those who have experienced a prior DAA treatment failure. [ABSTRACT FROM AUTHOR]

About 5% of chronic hepatitis C (CHC) patients experienced treatment failure with direct-acting antiviral (DAA) treatment. The global data on the practice and treatment outcomes of Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) in DAA-experienced CHC patients remains sparse. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of SOF/VEL/VOX as a salvage treatment in DAA-experienced CHC patients. We searched five electronic databases from inception to 31 January 2023. The study outcomes were SVR12 and treatment-related adverse effects, with subgroup analysis performed based on genotype, cirrhosis, HCC, prior SOF/VEL exposure, and region. We identified and analyzed data from 24 studies (2877 DAA-experienced CHC patients); 17.2% had prior SOF/VEL exposure, 25% received ribavirin with SOF/VEL/VOX, and 42% had pre-treatment resistance-associated substitution (RAS) testing performed. Eastern Mediterranean had a higher pooled SVR12 than the America and Europe regions (p < 0.05). Predictors of SOF/VEL/VOX failure were genotype 3, active HCC, baseline cirrhosis, and prior SOF/VEL. Baseline RAS mutation and ribavirin supplementation were not associated with higher SVR12. Treatment discontinuation because of drug-related adverse events was uncommon (10 studies, 0.2%). In summary, SOF/VEL/VOX is efficacious and safe for retreatment in DAA-experienced CHC patients, even with RAS mutation. Our findings support SOF/VEL/VOX as a first-line rescue treatment for DAA-experienced CHC patients. [ABSTRACT FROM AUTHOR]

Variations in the hepatitis C virus (HCV) core sequence have been related to disease progression and response to antiviral therapy. Previously we showed that the methylation status of RASSF1A and p16 genes, and IL28B genotypes affects the response to pegylated interferon/ribavirin (PEG-IFN/RBV) therapy. Herein we investigated whether amino acid (aa) substitutions in the HCV core region alone or in combination with IL28B genotypes and RASSF1A/p16 methylation affect the response to PEG-IFN/RBV therapy and liver disease progression. Among 29 examined patients, we found no association between single aa substitutions and response to therapy. However, we observed that patients with the HCV core aa substitution at position 75 and CT/TT IL28B genotypes were non-responders (NR), (P=0.023). Moreover, these patients had unmethylated RASSF1A. In contrast, most patients (75%) with aa substitutions at position 91 and CC IL28B genotype achieved sustained virologic response (SVR), (P=0.030), and 70% of them had methylated RASSF1A gene. Our results suggest that combined analysis of aa substitutions in the core protein, the IL28B rs12979860 polymorphism, and the methylation status of the RASSF1A gene may help in predicting treatment response to PEG-IFN/RBV in genotype 1b chronic hepatitis C patients. [ABSTRACT FROM AUTHOR]

N',N''-Bis[(E)-phenylmethylidene]carbonic dihydrazide, azotic ligands with lone electron pairs, have wide range of applications in catalysis, medicine, corrosion, and analytical chemistry. Keeping this broad range of applications in view, we have developed a new green method for the rapid synthesis of N',N''-Bis[(E)-phenylmethylidene]carbonic dihydrazide and its derivatives. By using a new protocol, a range of carbonic dihydrazides 1-22 has been synthesized in excellent yields. All synthesized compounds have been characterized by elemental analyses, 1H-NMR, EIMS and HR-MS. These carbonic dihydrazides have also been synthesized via conventional method. On comparisons of new and conventional methods, it is evident that newly developed solvent-free method is more proficient, high yielding, and simple. As protease inhibitors are known to inhibit not only proliferation of cancer cell lines but also to cure hepatitis C virus and HIV aids infections, therefore, all purified and characterized compounds have also been evaluated for their potential to act as in vitro α-chymotrypsin (an enzyme belongs to protease family) inhibitors. Among tested compounds, ten compounds have shown varying degree of αchymotrypsin inhibition potential. [ABSTRACT FROM AUTHOR]

The article focuses on the Encephalitis caused by Borna Disease Virus 1 (BoDV-1), which has been identified as a pathogen causing severe brain inflammation in humans since 2018. It mentions emergence of BoDV-1 as a human pathogen, its transmission, clinical symptoms, and the diagnostic challenge. It emphasize the importance of serological testing in addition to direct pathogen detection and neither a vaccine nor an approved therapy for this condition, which has a high fatality rate.

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Background: Human respiratory syncytial virus (HRSV) is a common cause of severe lower respiratory tract infections in infants and young children. There is no vaccine or effective treatment for this viral infection. However, Short hairpin RNA (shRNA) has many therapeutic applications, such as an effective treatment for viral infections. To find novel strategies to combat HRSV replication, specific shRNA targeting the HRSV fusion (F) gene was generated in the present study. The results were compared to ribavirin, the only Food and Drug Administration-approved antiviral drug to treat HRSV infection. Methods: ShRNA targeting a highly conserved region of the HRSV-F gene was designed to inhibit HRSV replication in vitro within the Hep-2 cell line. Real-time polymerase chain reaction (PCR) was performed to quantify virus replication and assess viral load reduction on harvested supernatant from Hep-2 cells infected with HRSV and treated with a scramble control vector, an shRNA vector, ribavirin, and a combination of ribavirin and shRNA of different concentrations at 24, 48, and 72 h after treatment. Results: Using real‑time reverse transcription PCR (RT‑PCR), a similar significant reduction in the viral load (99.8%) was observed by the effect of shRNA or ribavirin compared to the control group (P = 0.008). Combination treatment of ribavirin and F-shRNA resulted in a significant reduction in viral load compared to treatment with ribavirin or F‑shRNA separately (P = 0.043). Conclusions: Our study demonstrated that shRNA against the F gene could potentially be used as a novel therapeutic agent for HRSV infection. [ABSTRACT FROM AUTHOR]

Ribavirin (RIB) was successfully determined by fluorescence spectroscopy upon its quenching to environment friendly phosphorus and nitrogen co-doped carbon quantum dots (PNQDs). Different analytical parameters affecting the fluorescence spectra have been optimized and validated in accordance to the ICH guidelines. The proposed method has provided an efficient tracing of the interaction between RIB molecules and the synthesized QDs in an acidic medium (off-mode). The RIB molecules have shown excellent sensitivity by quenching of the emission band at 401 nm upon excitation at 245 nm throughout a linear range of 0.06–10.00 µg/mL with detection and quantitation limits down to 14.00 and 40.00 ng/mL, respectively. The quenching mode was proven to be static in raw samples and samples extracted of spiked plasma for quenching rate constants of 1.30 × 1012 L M−1 S−1 and 1.73 × 1012 L M−1 S−1, respectively. The proposed method has been successfully applied for determination of RIB in the commercial capsules and spiked human plasma samples with good recovery percentages in between 102.00 and 103.00%. Interestingly, these carbon dots have been utilized as nano-fluorescent platforms for assessment of the binding interaction kinetics between the RIB molecules and salmon sperm DNA (ssDNA). This has been implemented through peeling off the RIB molecules from surface of the PNQDs upon successive addition of the ssDNA and hence fluorescence restoration (turning on). Consequently, this provides a successful monitoring of its antimicrobial potency. It was evidenced a strong binding interaction with a binding constant of 2.38 × 104 mol−1/L. Significantly, this could open doors for an extended application for on-site monitoring of RIB as well as its interactions with biomolecules and microorganisms. [ABSTRACT FROM AUTHOR]

Tick-borne encephalitis virus (TBEV) belonging to arboviruses is a major member of zoonotic pathogens. TBEV infection causes severe human encephalitis without specific antiviral drugs. Due to its use of antiviral drug against a wide range of viruses, we investigated antiviral effect of ribavirin against TBEV in susceptible human cell lines A549 and SH-SY5Y. Ribavirin displayed minor cytotoxicity on multiple cell lines. Ribavirin obviously impaired TBEV replication and protected the infected cells from cytopathic effect. Importantly, ribavirin markedly inhibited TBEV propagation, as evidenced by impairment of TBEV production and viral RNA replication. Treatment with ribavirin (co-treatment and post-treatment) led to a dose-dependent reduction in TBEV titers as well as the viral RNA levels. Antiviral protein myxovirus resistance A mRNA expression was significantly upregulated and signal transducer and activator of transcription 3 was activated in TBEV-infected A549 cells upon the ribavirin treatment. Induction of inflammatory cytokine tumor necrosis factor alpha by TBEV was decreased in A549 cells with the treatment of ribavirin, whereas interleukin 1 beta release appeared to be unaffected. These results suggest that ribavirin might represent a promising safe and effective antiviral drug against TBEV. [ABSTRACT FROM AUTHOR]

This research has developed a piece of sanitizing locker-model equipment for textiles exposed to avian coronavirus, which has been put under the influence of UV light, UV + zinc oxide nanoparticles (phytosynthesized ZnONP), and water + UV, and, in turn, under the influence of the exposure time (60, 120, 180 s). The results linked to the phytosynthesis of ZnONP indicate a novel method of fabricating nanostructured material, nanoparticles with spherical morphology and an average size of 30 nm. The assays were made based on the viral viability of avian coronavirus according to the mortality of SPF embryonated eggs and a Real-Time PCR for viral load estimation. This was a model to evaluate the sanitizing effects against coronaviruses since they share a very similar structure and chemistry with SAR-CoV-2. The influence of the type of textile treatment evidenced the potential effect of the sanitizing UV light, which achieved 100% of embryo viability. The response of the ZnONP + UV nebulization showed a notorious influence of photoactivation according to the exposure time, and the 60-s treatment achieved a decrease of 88.9% in viral viability, compared to 77.8% and 55.6% corresponding to the 120 and 180-s treatments, respectively. Regarding the decrease in viral load between the types of treatments, UV 180 s reduced 98.42% and UV 60 s + ZnONP reduced 99.46%, respectively. The results show the combinatorial effect of UV light and zinc nanoparticles in decreasing the viral viability of avian coronavirus, as a model of other important coronaviruses in public health such as SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Numerous reports have explored the roles of different genetic variants in miRNA biogenesis mechanisms and the progression of various types of carcinomas. The goal of this study is to explore the association between XPO5*rs34324334 and RAN*rs14035 gene variants and susceptibility to hepatocellular carcinoma (HCC). In a cohort of 234 participants (107 HCC patients and 127 unrelated cancer-free controls) from the same geographic region, we characterized allelic discrimination using PCR-RFLP and performed subgroup analysis and multivariate regression. We found that the frequency of the XPO5*rs34324334 (A) variant was correlated with elevated risk of HCC under allelic (OR = 10.09, p-value < 0.001), recessive (OR = 24.1, p-value < 0.001), and dominant (OR = 10.1, p-value < 0.001) models. A/A genotype was associated with hepatitis C cirrhosis (p-value = 0.012), ascites (p-value = 0.003), and higher levels of alpha-fetoproteins (p-value = 0.011). Carriers of the RAN*rs14035 (T) variant were more likely to develop HCC under allelic (OR = 1.76, p-value = 0.003) and recessive (OR = 3.27, p-value < 0.001) models. Our results suggest that XPO5*rs34324334 and RAN*rs14035 variants are independent risk factors for developing HCC. [ABSTRACT FROM AUTHOR]

The current study attempted to evaluate the potential of fifty-three (53) natural compounds as Nipah virus attachment glycoprotein (NiV G) inhibitors through in silico molecular docking study. Pharmacophore alignment of the four (4) selected compounds (Naringin, Mulberrofuran B, Rutin and Quercetin 3-galactoside) through Principal Component Analysis (PCA) revealed that common pharmacophores, namely four H bond acceptors, one H bond donor and two aromatic groups were responsible for the residual interaction with the target protein. Out of these four compounds, Naringin was found to have the highest inhibitory potential (– 9.19 kcal mol−1) against the target protein NiV G, when compared to the control drug, Ribavirin (– 6.95 kcal mol−1). The molecular dynamic simulation revealed that Naringin could make a stable complex with the target protein in the near-native physiological condition. Finally, MM-PBSA (Molecular Mechanics-Poisson–Boltzmann Solvent-Accessible Surface Area) analysis in agreement with our molecular docking result, showed that Naringin (– 218.664 kJ mol−1) could strongly bind with the target protein NiV G than the control drug Ribavirin (– 83.812 kJ mol−1). [ABSTRACT FROM AUTHOR]

The present study evaluates the influence of type 2 diabetes (T2D) on important CYP450 (CYP) isoforms and P‐glycoprotein (Pgp) transporter activities before and 3 months after an intensifying treatment regimen involving 40 patients. Results have been compared with 21 non‐T2D healthy participants (the control group). CYPs and Pgp activities were assessed after administering the Geneva cocktail. The mean metabolic ratios (MR) for CYP2B6 (1.81 ± 0.93 versus 2.68 ± 0.87), CYP2C19 (0.420 ± 0.360 versus 0.687 ± 0.558) and CYP3A4/5 (0.487 ± 0.226 versus 0.633 ± 0.254) significantly decreased in T2D patients compared to the control group (p < 0.05). CYP2C9 (0.089 ± 0.037 versus 0.069 ± 0.017) activities slightly increased in diabetic patients, and no difference was observed regarding CYP1A2 (0.154 ± 0.085 versus 0.136 ± 0.065), CYP2D6 (1.17 ± 0.56 versus 1.24 ± 0.83), and Pgp activities in comparison to the control group. Three months after the intensifying treatment regimen, MRs of CYP2C9 (0.080 ± 0.030) and CYP3A4/5 (0.592 ± 0.268) improved significantly and were not statistically different compared to the control group (P > 0.05). Several covariables, such as inflammatory markers (IL‐1β and IL‐6), genotypes, diabetes and demographic‐related factors, were considered in the analyses. The results indicate that chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform‐specific manner. [ABSTRACT FROM AUTHOR]

Background: The goal of HCV treatment is eradication of the virus to prevent complications associated with the disease and decrease all-cause mortality. This work compared sustained viral response (SVR) 12 weeks after end of treatment of chronic HCV patients with different treatment regimens, namely 4 regimens. Two hundred treatment naive chronic HCV patients were selected and divided into 4 equal groups as follows: group A received pegylated interferon (peg IFN) and ribavirin (RBV); group B received peg IFN, RBV, and sofosbuvir (SOF); group C received RBV and SOF; group D received SOF, daclatasvir (DCV), and RBV. Results: The sustained viral response after 12 months of treatment is 57.23%, 72.09%, 64.40%, and 96.42% of patients in groups A, B, C, and D, respectively. Hence, group D regimen showed the best results. Conclusion: SOF and DCV and RBV have the highest SVR12 and least side effects compared to other treatment regimens. Although group D patients initially had poor pretreatment investigations relative to other groups, they proved to have the highest tolerability to this regimen. Such findings hold promising line of treatment and better prognosis even for chronic HCV patients with poor liver condition. [ABSTRACT FROM AUTHOR]

Among the seven coronaviruses that infect humans, HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 usually cause mild and common cold symptoms; however, infection with three coronaviruses, namely severe acute respiratory syndrome coronavirus [SARS-CoV], Middle East respiratory syndrome coronavirus [MERS-CoV], and the newly identified severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], often results in respiratory distress, cytokine storm and multiorgan failure [[1]]. Group 2b SARS-like coronaviruses represent a threat to global health, as evidenced by the emergence of SARS-CoV in 2002 and SARS-CoV-2 in 2019 [[2]]. Lopinavir and ritonavir, drugs used in the treatment of HIV, were proven effective against SARS-CoV [[13]], SARS-CoV-2, and MERS-CoV [[14]] through various in vitro and animal studies. Lopinavir has been shown to inhibit SARS-CoV, MERS-CoV, and SARS-CoV-2, with EC SB 50 sb concentrations of 17.1, 8 and 26 M, respectively [[16]]. [Extracted from the article]

Respiratory Syncytial Virus (RSV) is the top cause of infant hospitalization globally, with no effective treatments available. Researchers have sought small molecules to target the RNA-dependent RNA Polymerase (RdRP) of RSV, which is essential for replication and transcription. Based on the cryo-EM structure of the RSV polymerase, in silico computational analysis including molecular docking and the protein-ligand simulation of a database, including 6554 molecules, is currently undergoing phases 1–4 of clinical trials and has resulted in the top ten repurposed compound candidates against the RSV polymerase, including Micafungin, Totrombopag, and Verubecestat. We performed the same procedure to evaluate 18 small molecules from previous studies and chose the top four compounds for comparison. Among the top identified repurposed compounds, Micafungin, an antifungal medication, showed significant inhibition and binding affinity improvements over current inhibitors such as ALS-8112 and Ribavirin. We also validated Micafungin's inhibition of the RSV RdRP using an in vitro transcription assay. These findings contribute to RSV drug development and hold promise for broad-spectrum antivirals targeting the non-segmented negative-sense (NNS) RNA viral polymerases, including those of rabies (RABV) and Ebola (EBOV). [ABSTRACT FROM AUTHOR]

Ophidian serpentoviruses, positive-sense RNA viruses in the order Nidovirales, are important infectious agents of both captive and free-ranging reptiles. Although the clinical significance of these viruses can be variable, some serpentoviruses are pathogenic and potentially fatal in captive snakes. While serpentoviral diversity and disease potential are well documented, little is known about the fundamental properties of these viruses, including their potential host ranges, kinetics of growth, environmental stability, and susceptibility to common disinfectants and viricides. To address this, three serpentoviruses were isolated in culture from three unique PCR-positive python species: Ball python (Python regius), green tree python (Morelia viridis), and Stimson's python (Antaresia stimsoni). A median tissue culture infectious dose (TCID50) was established to characterize viral stability, growth, and susceptibility. All isolates showed an environmental stability of 10–12 days at room temperature (20 °C). While all three viruses produced variable peak titers on three different cell lines when incubated at 32 °C, none of the viruses detectably replicated at 35 °C. All viruses demonstrated a wide susceptibility to sanitizers, with 10% bleach, 2% chlorhexidine, and 70% ethanol inactivating the virus in one minute and 7% peroxide and a quaternary ammonium solution within three minutes. Of seven tested antiviral agents, remdesivir, ribavirin, and NITD-008, showed potent antiviral activity against the three viruses. Finally, the three isolates successfully infected 32 unique tissue culture cell lines representing different diverse reptile taxa and select mammals and birds as detected by epifluorescent immunostaining. This study represents the first characterization of in vitro properties of growth, stability, host range, and inactivation for a serpentovirus. The reported results provide the basis for procedures to mitigate the spread of serpentoviruses in captive snake colonies as well as identify potential non-pharmacologic and pharmacologic treatment options for ophidian serpentoviral infections. [ABSTRACT FROM AUTHOR]

The total alcohol extract obtained from the aerial parts of R. stricta and fractions of the liquid–liquid fractionation process were tested against picornavirus-causing foot-and-mouth disease (FMD) based on the traditional use of the plant in Saudi Arabia. The most active petroleum ether soluble fraction was subjected to chromatographic purification, and nine compounds were isolated, identified using various chemical and spectroscopic methods, and tested for their anti-viral potential. The new ester identified as α-Amyrin 3-(3′R-hydroxy)-hexadecanoate (1) was the most active compound with 51% inhibition of the viral growth and was given the name Rhazyin A. Compounds with ursane skeleton were more active than those with lupane skeleton except in the case of the acid derivatives where betulenic acid showed 26.1% inhibition against the viral growth, while ursolic acid showed only 16.6% inhibition. Moreover, molecular docking analysis using a glide extra-precision module was utilized for investigating the possible molecular interactions accounting for anti-viral activity against picornavirus of the nine isolated compounds. Molecular docking studies revealed a strong binding of the discovered hits within the active site of FMDV 3Cpro. Compound 1 showed the lowest docking score within the nine isolated compounds comparable to the two known anti-viral drugs; glycyrrhizic acid and ribavirin. The results of this research will provide lead candidates from natural origin with potential safety and efficacy compared to the synthetic ones with lower production costs for managing FMVD. [ABSTRACT FROM AUTHOR]

Currently, the only approved hepatitis C virus (HCV) treatment for children aged

Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disorder because of the persistence of mutated measles virus in the central nervous system. Till date, no curative therapy has been established for SSPE. Multiple drugs have been tried to modify the disease process but have shown mild to moderate benefit at best. It is also challenging to attribute the relative success of some strategies described in single case reports because of the known phenomenon of spontaneous improvement in 5% of patients with SSPE. Critical gaps in understanding the pathophysiological processes involved exist. Current therapies such as interferon alfa require invasive strategies for administration by the intraventricular or intrathecal route, with varying dosage regimens. Oral therapies such as isoprinosine and ribavirin are expensive and not readily available in resource-constrained settings. Most of the evidence so far favors the use of combinational regimens. In this viewpoint, we critically summarize the current evidence on disease-modifying strategies in the context of our region.

The COVID-19 pandemic has caused havoc in the health sector. Inflammatory cytokines play an important role in the disease condition. Existing evidence has provided certain insights into the repurposing of the drugs. This meta-analysis and systematic review aimed to explore the efficacy of the administration of interferon beta-1b (IFN β-1b) and standard care versus only standard care as the therapeutic agent for managing COVID-19 patients who are severely ill. The search was conducted in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Scopus, and Google Scholar, which were published during the period January 1, 2020, to February 16, 2023. All the included three studies were independently assessed for eligibility. The modified data extraction form of Cochrane were used. The quality of the three included studies was assessed using the Cochrane risk of bias tool. GradePro software was used to summarize the quality grading of the primary outcome measures. The time taken for clinical improvement was (MD: -3.28 days; 95% CI: -5.65, -0.91; P value = 0.007) when treated with IFN β-1b. The duration of hospital stays (MD: -2.43 days; 95% CI: -4.45, -0.30; P value = 0.03), and need for intensive care unit (ICU) admission (RR: 0.71; 95% CI: 0.52, 0.97; P value = 0.03) was statistically significant. Interferon beta-1b is proven to reduce the duration of hospital stay, and the improved clinical status may become a cornerstone of COVID-19 treatment.