SARS‐CoV‐2 Papain‐Like Protease: Structure, Function and Inhibition

ChemBioChem, Год журнала: 2022, Номер 23(19)

Опубликована: Авг. 22, 2022

Abstract Emerging variants of SARS‐CoV‐2 and potential novel epidemic coronaviruses underline the importance investigating various viral proteins as drug targets. The papain‐like protease has been less explored than other proteins; however, its substantive role in replication impact on host immune response make it a suitable target to study. This review article focuses structure function (PL pro ) SARS‐CoV‐2, including concern, compares those coronaviruses, such SARS‐CoV‐1 MERS‐CoV. protease's recognition motif is mirrored ubiquitin ISG15, which are involved antiviral response. Inhibitors, GRL0617 derivatives, their prospects future agents also discussed.

Язык: Английский

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Androgen receptor, a possible anti-infective therapy target and a potent immune respondent in SARS-CoV-2 spike binding: a computational approach

Expert Review of Anti-infective Therapy, Год журнала: 2023, Номер 21(3), С. 317 - 327

Опубликована: Фев. 9, 2023

Although androgen in gender disparity of COVID-19 has been implied, no direct link provided.Here, we applied AlphaFold multimer, network and single cells database analyses to highlight specificity Androgen receptor (AR) against spike binding protein (RBD) SARS-CoV-2.LXXL motifs RBD are essential for AR binding. LXXA mutation complex with the depicting slightly reduced energy, as LXXLL motif usually mediates nuclear coregulators. Moreover, preferred bind a LYRL interaction interface, showed affinity Omicron compared other variants (alpha, beta, gamma, delta). Importantly, is conserved antigenic epitope (9 residues) T-cell response. Network analysis AR-related genes signaling regulation, CD8+ spatial location AR+ cells, which consistent function.We provided potent mechanisms linking immune response vaccination shift. could be an anti-infective therapy target anti-Omicron new lineages.

Язык: Английский

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Colorectal Cancer Risk Prediction Using the rs4939827 Polymorphism of the SMAD7 Gene in the Romanian Population

Diagnostics, Год журнала: 2024, Номер 14(2), С. 220 - 220

Опубликована: Янв. 19, 2024

Colorectal cancer (CRC) is globally recognized as a prevalent malignancy known for its significant mortality rate. Recent years have witnessed rising incidence trend in colorectal cancer, emphasizing the necessity early diagnosis. Our study focused on examining impact of SMAD7 gene variant rs4939827 risk occurrence. The composition our group included 340 individuals, comprising 170 CRC diagnosed patients and healthy controls. We performed genotyping all biological samples using TaqMan assay ABI 7500 Real-Time PCR System (Applied Biosystems, Waltham, MA, USA). This investigation variant, assessing association with clinicopathological characteristics. Genotyping results revealed 42.6% prevalence C allele (p = 0.245) 22.8% T control subjects 0.109). concluded that there was an elevated dominant model CC/CT+TT, p-value 0.113 odds ratio (OR) 2.781, within 95% confidence interval (CI) 0.998 to 3.456. findings research indicate correlation between variants likelihood developing population. Consequently, these could be instrumental facilitating diagnosis utilizing information single-nucleotide polymorphism (SNP) genetic susceptibility disease.

Язык: Английский

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Risk of Admission to the Pediatric Intensive Care Unit for SARS-CoV-2 Delta and Omicron Infections

Journal of the Pediatric Infectious Diseases Society, Год журнала: 2023, Номер 12(4), С. 189 - 197

Опубликована: Фев. 14, 2023

The severity of SARS-CoV-2-related diseases in children remains unclear. This study aimed to describe the incidence French pediatric intensive care units (PICUs) admissions with acute COVID-19, incidental positive SARS-CoV-2 test result, and multisystem inflammatory syndrome (MIS-C) during delta omicron variant periods.This used PICU registry obtain data on all patients admitted 41 PICUs diagnosed or MIS-C between August 30, 2021 April 20, 2022. Data regarding total number polymerase chain reaction results according type variants were obtained from National Public Health Agency.Of 745 children, 244 (32.8%) for 246 (33.0%) results, 255 (34.2%) MIS-C. each group was higher than omicron. rate ratios 7.47 (95% CI, 4.22-13.26) 4·78 2.30-9.94) 10.46 5.98-18.31) compared variant. median age 66 (7.7-126.8) months; 314 (42%) had comorbidities. Patients COVID-19 similar proportions No patient died, whereas mortality rates groups 6.8% 3.8%, respectively.The significantly

Язык: Английский

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Risk Factors for Severe and Critical Coronavirus Disease 2019 in Children

The Pediatric Infectious Disease Journal, Год журнала: 2024, Номер 43(3), С. 234 - 241

Опубликована: Янв. 18, 2024

Background: Coronavirus disease 2019 (COVID-19) is generally mild in children; however, severe or critical cases may occur. In this nationwide study, we analyzed clinical manifestations children diagnosed with acute respiratory syndrome coronavirus 2 to identify high-risk groups for and compared the features between Delta- Omicron-dominant periods. Methods: Data were retrieved from National Health Insurance Service (NHIS) database merged Korea Disease Control Prevention Agency-COVID-19-NHIS cohort, which includes information on COVID-19 vaccination records. We included individuals <20 years old during both periods (Delta: July 25, 2021–January 15, 2022; Omicron: January 16, 2022–March 31, 2022). Results: Proportion of was higher Delta period than Omicron period. The saw increased hospitalization pneumonia croup likelihood neurological manifestations. risk depended age group highest 12–19 years; 0–4 years). This high multiple complex chronic conditions obesity asthma but not Two-dose provided strong protection against (adjusted odds ratio: 0.20), reduced effectiveness 0.91). However, it significantly illness 0.14). Conclusions: These findings can facilitate identification at COVID-19, who require intensive medical support, development policies.

Язык: Английский

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Unravelling Insights into the Evolution and Management of SARS-CoV-2

BioMedInformatics, Год журнала: 2024, Номер 4(1), С. 385 - 409

Опубликована: Фев. 3, 2024

Worldwide, the COVID-19 pandemic, caused by brand-new coronavirus SARS-CoV-2, has claimed a sizable number of lives. The virus’ rapid spread and impact on every facet human existence necessitate continuous dynamic examination its biology management. Despite this urgency, does not currently have any particular antiviral treatments. As result, scientists are concentrating repurposing existing medications or creating ones. This comprehensive review seeks to provide an in-depth exploration our current understanding starting with analysis prevalence, pathology, evolutionary trends. In doing so, aims clarify complex network factors that contributed varying case fatality rates observed in different geographic areas. work, we explore world SARS-CoV-2 mutations their implications for vaccine efficacy therapeutic interventions. viral landscape pandemic poses significant challenge, leading investigate genetic foundations virus mechanisms underlying these alterations. Numerous hypotheses been proposed as developed, covering various subjects like selection pressures driving mutation, possibility escape, consequences clinical therapy. Furthermore, will shed light trials investigating novel medicines development, including promising field drug repurposing, providing window into changing treatment approaches. study provides compiling huge evolving body knowledge highlighting complexities public health, igniting additional investigation control unprecedented global health disaster.

Язык: Английский

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Infection kinetics, syncytia formation, and inflammatory biomarkers as predictive indicators for the pathogenicity of SARS-CoV-2 Variants of Concern in Calu-3 cells

PLoS ONE, Год журнала: 2024, Номер 19(4), С. e0301330 - e0301330

Опубликована: Апрель 3, 2024

The ongoing COVID-19 pandemic has led to the emergence of new SARS-CoV-2 variants as a result continued host-virus interaction and viral genome mutations. These have been associated with varying levels transmissibility disease severity. We investigated phenotypic profiles six (WT, D614G, Alpha, Beta, Delta, Omicron) in Calu-3 cells, human lung epithelial cell line. In our model demonstrated that all variants, except for Omicron, had higher efficiency virus entry compared wild-type. Delta variant greatest advantage terms early infection kinetics marked syncytia formation, which could facilitate cell-to-cell spreading, while Omicron displayed slower replication fewer formation. also identified strongest inducer inflammatory biomarkers, including pro-inflammatory cytokines/chemokines (IP-10/CXCL10, TNF-α, IL-6), anti-inflammatory cytokine (IL-1RA), growth factors (FGF-2 VEGF-A), these mediators were not significantly elevated infection. findings are consistent observations there was generally more pronounced response angiogenesis activity within lungs patients well severe symptoms mortality rate during wave, less lower observed current wave Thailand. Our suggest infectivity kinetics, enhanced specific mediator production may serve predictive indicators virulence potential future variants.

Язык: Английский

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Mosaic Recombination Inflicted Various SARS-CoV-2 Lineages to Emerge into Novel Virus Variants: a Review Update

Indian Journal of Clinical Biochemistry, Год журнала: 2022, Номер 38(4), С. 418 - 425

Опубликована: Дек. 17, 2022

Язык: Английский

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Kinetics of severe acute respiratory syndrome coronavirus 2 infection antibody responses

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Авг. 5, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world, causing severe morbidity and mortality. Since first reports of Coronavirus disease 2019 (COVID-19) in late 2019, research on characteristics specific humoral immunity against SARS-CoV-2 patients with COVID-19 made great progress. However, our knowledge persistent to infection is limited. The existence protective after will affect future transmission severity. Therefore, it important gather about kinetics antibody responses. In this review, we summarize information obtained so far immune response, especially neutralizing antibodies their relationship addition, emergence variants concern, effect concern initial vaccination.

Язык: Английский

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Towards Efficient and Accurate SARS-CoV-2 Genome Sequence Typing Based on Supervised Learning Approaches

Microorganisms, Год журнала: 2022, Номер 10(9), С. 1785 - 1785

Опубликована: Сен. 4, 2022

Despite the active development of SARS-CoV-2 surveillance methods (e.g., Nextstrain, GISAID, Pangolin), global emergence various viral lineages that potentially cause antiviral and vaccine failure has driven need for accurate efficient genome sequence classifiers. This study presents an optimized method accurately identifies sequences using existing schemes. For Nextstrain GISAID clades, a template matching-based is proposed to quantify differences between clades play important role in classification evaluation. Furthermore, improve typing accuracy sequences, ensemble model integrates combination machine learning-based (such as Random Forest Catboost) with weights Pangolin, clades. Cross-validation applied optimize parameters weight settings model. To efficiency model, addition one-hot encoding method, we have nucleotide site mutation-based data structure requires less computational resources performs better typing. Based on accumulated database >1 million performance evaluations show system 99.879%, 97.732%, 96.291% respectively. A single prediction only takes average <20 ms portable laptop. Overall, this provides benefits current future variants.

Язык: Английский

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