The Ability of Combined Flavonol and Trihydroxyorganic Acid to Suppress SARS-CoV-2 Reproduction DOI Creative Commons
Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk

et al.

Viruses, Journal Year: 2024, Volume and Issue: 17(1), P. 37 - 37

Published: Dec. 30, 2024

The global burden of COVID-19 continues to rise, and despite significant progress in vaccine development, there remains a critical need for effective treatments the severe inflammation acute lung injury associated with SARS-CoV-2 infection. In this study, we explored antiviral properties plant-derived complex consisting flavonol hydroxyorganic acid compounds. Our research focused on ability suppress activity several key proteins involved replication maturation SARS-CoV-2. These include ACE2 protein, HRV 3C Protease, Mpro (Main Protease). It was shown that plant-based effectively inhibited these viral proteins. addition its effects proteins, were Vero E6 cells. At dose 22 μg/mL, drug demonstrated maximum activity, significantly reducing vitro. preliminary studies, showed both prophylactic therapeutic potential, suggesting it may be useful preventing infection, as well severity disease once an individual has been infected Based compelling results propose potential compound Its inhibit exhibit protective positions valuable candidate further clinical evaluation. As fight against continues, therapies like could complement existing provide new options managing treating disease.

Language: Английский

Comparative Analysis of Neuropsychiatric Adverse Reactions Associated with Remdesivir and Nirmatrelvir/Ritonavir in COVID-19 Treatment: Insights from EudraVigilance Data DOI Open Access

Aliteia-Maria Pacnejer,

M.E. Negru, Anca Maria Arseniu

et al.

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(6), P. 1886 - 1886

Published: March 11, 2025

Remdesivir (RDV) and nirmatrelvir/ritonavir (NMVr) are among the most widely used antivirals in treatment of COVID-19, aiming to reduce disease severity progression. Adverse neuropsychiatric effects, such as anxiety, sleep disturbances, movement disorders, have emerged significant concerns associated with these treatments. To better understand safety profiles RDV NMVr, this study performs a pharmacovigilance analysis individual case reports (ICSRs) from EudraVigilance (EV) database. Objectives: This evaluates risk adverse events NMVr. Comparisons other antiviral drugs, including darunavir, sofosbuvir, ribavirin, tenofovir, ritonavir, sotrovimab, also performed develop comprehensive understanding profiles. Methods: A retrospective ICSRs submitted EV until 7 July 2024, data extraction on 12 was conducted. Demographic characteristics (age, sex, geographic region, reporter type) were included descriptive analysis. Disproportionality using reporting odds ratio (ROR) 95% confidence intervals (CI) compare drug reaction (ADRs) frequencies across 27 system organ classes (SOCs), emphasis “Nervous disorders” “Psychiatric disorders. Results: The total number significantly higher for NMVr (n = 8078) compared 3934). Nervous disorders accounted 3.07% 17.31% reports, while psychiatric represented 0.92% ADRs reported 60) 3.61% 672). On hand, showed lower frequency headache (ROR: 0.1057; CI: 0.0676–0.1653). Conclusions: presents than RDV, underscoring need enhanced monitoring, particularly patients preexisting central nervous (CNS) conditions. These findings contribute optimizing informing clinical decision making.

Language: Английский

Citations

1
From Detection to Protection: Antibodies and Their Crucial Role in Diagnosing and Combatting SARS-CoV-2 DOI Creative Commons
Anoop Kumar, Prajna Tripathi, Prashant Kumar

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(5), P. 459 - 459

Published: April 25, 2024

Understanding the antibody response to SARS-CoV-2, virus responsible for COVID-19, is crucial comprehending disease progression and significance of vaccine therapeutic development. The emergence highly contagious variants poses a significant challenge humoral immunity, underscoring necessity grasping intricacies specific antibodies. This review emphasizes pivotal role antibodies in shaping immune responses their implications diagnosing, preventing, treating SARS-CoV-2 infection. It delves into kinetics characteristics explores current antibody-based diagnostics, discussing strengths, clinical utility, limitations. Furthermore, we underscore potential SARS-CoV-2-specific antibodies, various therapies such as monoclonal polyclonal anti-cytokines, convalescent plasma, hyperimmunoglobulin-based therapies. Moreover, offer insights vaccines, emphasizing neutralizing order confer immunity along with emerging concern (VOCs) circulating Omicron subvariants. We also highlight challenges field, risks antibody-dependent enhancement (ADE) shed light on associated original antigenic sin (OAS) effect long COVID. Overall, this intends provide valuable insights, which are advancing sensitive diagnostic tools, identifying efficient therapeutics, developing effective vaccines combat evolving threat global scale.

Language: Английский

Citations

5
Does early combination vs. Monotherapy improve clinical outcomes of clinically extremely vulnerable patients with COVID-19? Results from a retrospective propensity-weighted analysis DOI Creative Commons
Maria Mazzitelli, Alberto Enrico Maraolo, Claudia Cozzolino

et al.

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: Oct. 4, 2024

Language: Английский

Citations

4
Structure–Activity Relationship of Ciprofloxacin towards S-Spike Protein of SARS-CoV-2: Synthesis and In-Silico Evaluation DOI
Sahil Kumar,

Papiya Dey,

Arup Kumar Pathak

et al.

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

The recent outbreak of the coronavirus (COVID-19) pandemic, caused by SARS-CoV-2 virus, has posed serious threats to global health systems. Although several directions have been put WHO for effective treatment, use antibiotics, particularly ciprofloxacin, in suspected and acquired Covid-19 patients raised an even more concern antibiotic resistance. Ciprofloxacin reported inhibit entry into host cells via interacting with spike (S) protein. However, a proper structure-activity relationship study ciprofloxacin S-protein is lacking, which inhibits researchers from developing potent fluoroquinolone analogue, specific inhibition viral entry. Herein, order study, we accomplished short convergent synthesis different derivatives detailed

Language: Английский

Citations

0
An ultra-long heavy chain bovine antibody neutralizes SARS-CoV-2 and reacts broadly with sarbecoviruses DOI Creative Commons
Theocharis Tsoleridis, Chengcheng Fan,

Emily J. Park

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract The threat of emergence further SARS-CoV-2 variants, and the future spillover potential other sarbecoviruses has prompted continued efforts to isolate broadly reactive monoclonal antibodies for therapeutic use. In this study, we generated from immunised cattle, primarily because their ability produce with ultra-long heavy chain complementarity determining region 3 (CDRH3) domains. Such have been shown potent cross-reactive neutralisation phenotypes in virus infections. Following extended immunisation different forms spike protein using single B-cell sorting phage display techniques, isolated 33 mAbs, including 10 CDRH3s (>50 amino acids). Of these, mAbs P7 99 exhibited remarkable breadth potency. Notably, mAb P7, which possessed an CDRH3, neutralised all tested SARS-CoV-1, IC 50 values ranging 0.01 µg/mL 1.06 µg/mL. This antibody was also against a panel RBDs diverse sarbecovirus species. Structural studies revealed that targets receptor-binding domain (RBD) overlaps ACE2 binding site. Although structure Fab-RBD complex not resolvable, data suggest induces trimer dissociation by occluded RBD epitope, likely mediated CDRH3 structure. Syrian hamster challenge experiments, several VOCs, showed significantly reduced lung viral load. These findings highlight bovine-derived, especially those possessing CDRH3s, as effective therapeutics current threats. One Sentence Summary Monoclonal derived cows exhibit pan-sarbecovirus reactivity, highlighting use

Language: Английский

Citations

0
Immunobiology and immunotherapy of COVID-19 DOI
Kenneth Lundström

Progress in molecular biology and translational science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Unveiling the Threat of Disease X: Preparing for the Next Global Pandemic DOI Open Access
Mengyuan Zhao,

Luping Lei,

Yinghan Jiang

et al.

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(2)

Published: Feb. 1, 2025

ABSTRACT The term “Disease X”, first introduced by the World Health Organization (WHO) in 2018, symbolizes threat of an unknown pathogen capable causing a global pandemic. Classified as “priority pathogens,” Disease X stands alongside well‐known threats like SARS, Ebola, and ZIKV due to its potential for widespread outbreaks. SARS‐CoV‐2 is considered X” fulfill this prediction, demonstrating devastating impact such pathogens can have. A future could pose even greater threat, with catastrophic consequences. This paper examines origins pathogens, drawing lessons from outbreaks MERS, SARS‐CoV‐2. It also highlights strategic approaches detect, prevent, respond effectively mitigate risk pandemics.

Language: Английский

Citations

0
Epimaps of the SARS-CoV-2 Receptor-Binding Domain Mutational Landscape: Insights into Protein Stability, Epitope Prediction, and Antibody Binding DOI Creative Commons
Eleni Pitsillou, Assam El‐Osta, Andrew Hung

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 301 - 301

Published: Feb. 18, 2025

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses an ongoing threat to the efficacy vaccines and therapeutic antibodies. Mutations predominantly affect receptor-binding domain (RBD) spike protein, which mediates viral entry. RBD is also a major target monoclonal antibodies that were authorised for use during pandemic. In this study, in silico approach was used investigate mutational landscape SARS-CoV-2 variants, including currently circulating Omicron subvariants. A total 40 single-point mutations assessed their potential effect on protein stability dynamics. Destabilising effects predicted such as L455S F456L, while stabilising R346T. Conformational B-cell epitope predictions subsequently performed wild-type (WT) variant RBDs. from located within residues regions found correspond sites targeted by Furthermore, homology models generated utilised protein-antibody docking. binding characteristics 10 against WT 14 evaluated. Through evaluating affinities, interactions, energy contributions residues, contributing evasion identified. findings study provide insight into structural molecular mechanisms underlying neutralising antibody evasion. Future development could focus broadly antibodies, engineering with enhanced affinity, targeting beyond RBD.

Language: Английский

Citations

0
Efficacy and Safety of Sotrovimab Versus Oral Antiviral for Early Treatment in High-Risk Patients in Omicron Era: A Multicenter Retrospective Study DOI Creative Commons
Antonio Russo, Mariantonietta Pisaturo,

Chiara Cacace

et al.

Pathogens, Journal Year: 2025, Volume and Issue: 14(3), P. 216 - 216

Published: Feb. 22, 2025

Introduction: High-risk patients with COVID-19 benefit from early treatment to prevent severe outcomes. Sotrovimab, a monoclonal antibody, and oral antivirals such as nirmatrelvir/ritonavir molnupiravir have been used for intervention, but their comparative efficacy safety, particularly during the Omicron-dominant phase, require further evaluation. Methods: A multicenter, retrospective study performed in southern Italy including all adult who received antiviral (sotrovimab or nirmatrelvir/r molnupiravir) between January 2022 February 2024 (omicron phase). Demographic, clinical, treatment-related data were analyzed assess primary endpoints of 28-day mortality hospitalization. Logistic regression models identified predictors key Results: total 668 high-risk treated sotrovimab (n = 326) 342: 69 273 nirmatrelvir/ritonavir) included. There was no significant difference groups (0.8% vs. 1.8% antivirals; p 0.679). However, exhibited longer median time SARS-CoV-2 negativization (13 11 days; 0.008) higher non–COVID-19-related hospitalizations (2.45% 0%; 0.003). Multivariable analysis cardiovascular cerebrovascular diseases sole predictor prolonged viral positivity (OR 1.585, 95% CI 1.072–2.345; 0.021). Additionally, immunocompromised status 16.929, 1.835–156.170; 0.013) chronic non-COVID-19 oxygen therapy 10.714, 1.623–70.725; 0.014) strongly associated mortality. Conclusions: Sotrovimab demonstrated similar preventing hospitalization among patients. Patient-specific factors, comorbidities immunosuppression, significantly influenced outcomes should guide choices.

Language: Английский

Citations

0
Development of antiviral drugs for COVID-19 in 2025: unmet needs and future challenges DOI
Daniele Focosi, David J. Sullivan, Massimo Franchini

et al.

Expert Review of Anti-infective Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

The success in the COVID-19 pandemic containment largely originated from vaccine- and infection-elicited immunity, with SARS-CoV-2 infection only marginally mitigated by availability of antiviral drugs. current lack effective prophylactic therapeutic agents immunocompromised patients highlights need for a radical change design both drug manufacturing clinical trials. In this review authors summarize their suggestions manufacturers, reviewing classes small molecule antivirals passive immunotherapies highlighting limitations unexploited potential. Molecular serological testing can improve appropriateness. Efficacy be improved combining different while preserving economical sustainability. Respiratory delivery should better investigated

Language: Английский

Citations

0