Glycyl-tRNA Synthetase as a Target for Antiviral Drug Screening Against Influenza Virus DOI Open Access
Jingjing Zhang, Xiaorong Li, Jingxian Liang

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 2912 - 2912

Опубликована: Март 23, 2025

Influenza viruses are characterized by their high variability and pathogenicity, effective therapeutic options remain limited. Given these challenges, targeting host cell proteins that facilitate viral replication presents a promising strategy for antiviral drug discovery. In the present study, we observed significant upregulation of Glycyl-tRNA synthetase (GlyRS) within 24 h post-PR8 virus infection. The inhibition GlyRS expression in A549 cells resulted marked reduction infection rates across multiple influenza strains, while overexpression led to an increase infectivity during early stages These findings suggest plays critical role virus. Accordingly, screened potential inhibitors identified Lycobetaine Scutellarein using multifaceted approach. Through combination molecular dynamics simulations, further elucidated mechanisms action binding sites compounds. Both effectively suppressed viruses, activity was confirmed be mediated targeting. Therefore, inhibitors, such as Scutellarein, represent candidates combating infections provide novel insights into treatment aaRS-related diseases, opening new avenues development aaRS-targeted therapeutics.

Язык: Английский

Molecular Mechanisms of Antiviral Agents against Dengue Virus DOI Creative Commons
Michelle Felicia Lee, Yuan Seng Wu, Chit Laa Poh

и другие.

Viruses, Год журнала: 2023, Номер 15(3), С. 705 - 705

Опубликована: Март 8, 2023

Dengue is a major global health threat causing 390 million dengue infections and 25,000 deaths annually. The lack of efficacy the licensed Dengvaxia vaccine absence clinically approved antiviral against virus (DENV) drive urgent demand for development novel anti-DENV therapeutics. Various agents have been developed investigated their activities. This review discusses mechanisms action employed by various DENV. host-directed antivirals targeting host receptors direct-acting DENV structural non-structural proteins are reviewed. In addition, that target different stages during post-infection such as viral replication, maturation, assembly Antiviral designed based on these molecular could lead to discovery therapeutics treatment infections. Evaluations combinations drugs with also synergistic drug at any stage infection.

Язык: Английский

Процитировано

56

Aryl hydrocarbon receptor is a proviral host factor and a candidate pan-SARS-CoV-2 therapeutic target DOI Creative Commons
Jiandong Shi, Tingfu Du, Junbin Wang

и другие.

Science Advances, Год журнала: 2023, Номер 9(22)

Опубликована: Май 31, 2023

The emergence of a series SARS-CoV-2 variants has necessitated the search for broad-spectrum antiviral targets. aryl hydrocarbon receptor (AhR) senses tryptophan metabolites and is an immune regulator. However, role AhR in infection whether can be used as target therapy against its are yet unclear. Here, we show that with activates signaling facilitates viral replication by interfering IFN-I-driven immunity up-regulating ACE2 expression. pharmacological blockade or knockout reduces variants' vitro. Drug targeting antagonists markedly reduced vivo ameliorated lung inflammation caused hamsters. Overall, was proviral host factor candidate host-directed variants, including Delta Omicron, potentially other future.

Язык: Английский

Процитировано

29

Recent Updates on Multifunctional Nanomaterials as Antipathogens in Humans and Livestock: Classification, Application, Mode of Action, and Challenges DOI Creative Commons
Samreen Sadiq, Iltaf Khan,

Zhenyu Shen

и другие.

Molecules, Год журнала: 2023, Номер 28(22), С. 7674 - 7674

Опубликована: Ноя. 20, 2023

Pathogens cause infections and millions of deaths globally, while antipathogens are drugs or treatments designed to combat them. To date, multifunctional nanomaterials (NMs), such as organic, inorganic, nanocomposites, have attracted significant attention by transforming antipathogen livelihoods. They very small in size so can quickly pass through the walls bacterial, fungal, parasitic cells viral particles perform their antipathogenic activity. more reactive a high band gap, making them effective than traditional medications. Moreover, due some pathogen’s resistance currently available medications, performance NMs is becoming crucial. Additionally, prospective properties administration methods, eventually chosen for cutting-edge applications therapies, including drug diagnostic tools antipathogens. Herein, characteristics that facilitate identifying eliminating pathogens real-time. This mini-review analyzes antimicrobial investigates mode action. We also discussed challenges need be solved utilization

Язык: Английский

Процитировано

24

Achieving Optimal Health With Host‐Directed Therapies (HDTs) in Infectious Diseases—A New Horizon DOI Creative Commons
Amol D. Gholap,

Pankaj R. Khuspe,

Sagar R. Pardeshi

и другие.

Advanced Therapeutics, Год журнала: 2024, Номер unknown

Опубликована: Сен. 18, 2024

Abstract Host‐directed therapies (HDTs) have emerged as a promising strategy to combat viral infections by modifying host factors and immune responses restrict replication improve patient outcomes. This review summarizes the latest advances future potential of HDTs in antiviral therapy. With developments genomics proteomics, new targets essential for been identified. Gene‐editing tools, such CRISPR‐Cas9, enable precise manipulation genes linked processes, paving way innovative HDTs. Emerging approaches, including RNA interference interference, further demonstrate specifically modify inhibit replication. Additionally, probiotics are being explored their capacity enhance modulate gut microbiota, offering natural safe method boosting defenses. Despite these advancements, significant challenges remain, particularly deciphering complex host–virus interactions ensuring safety efficacy therapies. Continued research clinical evaluation realize full provides comprehensive overview current HDT strategies, emphasizing promise shaping interventions.

Язык: Английский

Процитировано

10

Transformative Approaches in SARS-CoV-2 Management: Vaccines, Therapeutics and Future Direction DOI
Ankita Saha,

Shweta Choudhary,

Priyanshu Walia

и другие.

Virology, Год журнала: 2025, Номер 604, С. 110394 - 110394

Опубликована: Янв. 11, 2025

Язык: Английский

Процитировано

1

Deciphering Host–Virus Interactions and Advancing Therapeutics for Chronic Viral Infection DOI Creative Commons
Majid Eslami,

Neda Arjmand,

Fatemeh Mahmoudian

и другие.

Viruses, Год журнала: 2025, Номер 17(3), С. 390 - 390

Опубликована: Март 10, 2025

Chronic viral infections like HIV, HBV, and HCV establish persistent interactions with the host immune system, resulting in evasion long-term dysfunction. These viruses use a range of strategies to limit defenses, such as downregulating MHC class I, disrupting interferon signaling, altering apoptosis pathways, suppressing cytotoxic T-cell activity. Key proteins, including HIV Nef, HBV X protein, NS5A, interfere antigen presentation JAK/STAT thereby reducing antiviral responses. induce exhaustion due exposure, which leads expression inhibitory receptors PD-1 CTLA-4 on T cells. Viral epigenetic changes, N6-methyladenosine modifications histone deacetylation, enhance by modulating gene infected Viruses further manipulate cytokine networks promoting an immunosuppressive environment through IL-10 TGF-β secretion, suppress inflammatory responses inhibit activation. This review examines molecular/cellular mechanisms that enable chronic escape immunity, focusing antigenic variation, disruption, control apoptotic pathways. It also addresses how genetic factors, HLA polymorphisms, influence disease progression. Lastly, we discuss host-targeted therapies, checkpoint inhibitors, treatments, CRISPR.

Язык: Английский

Процитировано

1

Applying genetic technologies to combat infectious diseases in aquaculture DOI Creative Commons
Nicholas A. Robinson, Diego Robledo, Lene Sveen

и другие.

Reviews in Aquaculture, Год журнала: 2022, Номер 15(2), С. 491 - 535

Опубликована: Сен. 5, 2022

Disease and parasitism cause major welfare, environmental economic concerns for global aquaculture. In this review, we examine the status potential of technologies that exploit genetic variation in host resistance to tackle problem. We argue there is an urgent need improve understanding mechanisms involved, leading development tools can be applied boost reduce disease burden. draw on two pressing problems as case studies-sea lice infestations salmonids white spot syndrome shrimp. review how latest capitalised upon determine underlying inter- intra-species pathogen/parasite resistance, derived knowledge could using selective breeding, gene editing and/or with targeted feed treatments vaccines. Gene brings novel opportunities, but also implementation dissemination challenges, necessitates new protocols integrate technology into aquaculture breeding programmes. There ongoing minimise risks agents evolving overcome improvements insights from epidemiological evolutionary models pathogen infestation wild cultured populations are explored. Ethical issues around different approaches achieving discussed. Application has fundamental affecting provide effective pathways lead more resistant stocks, transforming

Язык: Английский

Процитировано

39

PROTACs in the Management of Prostate Cancer DOI Creative Commons

Yedla Poornachandra,

Ahmad O. Babalghith,

Vindhya Vasini Andra

и другие.

Molecules, Год журнала: 2023, Номер 28(9), С. 3698 - 3698

Опубликована: Апрель 25, 2023

Cancer treatments with targeted therapy have gained immense interest due to their low levels of toxicity and high selectivity. Proteolysis-Targeting Chimeras (PROTACs) drawn special attention in the development cancer therapeutics owing unique mechanism action, ability target undruggable proteins, focused engagement. PROTACs selectively degrade protein through ubiquitin-proteasome system, which describes a different mode action compared conventional small-molecule inhibitors or even antibodies. Among types, prostate (PC) is most prevalent non-cutaneous men. Genetic alterations overexpression several genes, such as FOXA1, AR, PTEN, RB1, TP53, etc., suppress immune response, resulting drug resistance drugs cancer. Since progression ARV-110 (PROTAC for PC) into clinical phases, focus research has quickly shifted degraders targeting The present review highlights an overview superiority over inhibitors. We also delve underlying pathophysiology disease explain structural design linkerology strategies PROTAC molecules. Additionally, we touch on various targets cancer, including androgen receptor (AR) other critical oncoproteins, discuss future prospects challenges this field.

Язык: Английский

Процитировано

19

Structural and Functional RNA Motifs of SARS-CoV-2 and Influenza A Virus as a Target of Viral Inhibitors DOI Open Access

Izabela Szczesniak,

Agnieszka Baliga-Gil,

Aleksandra Jarmolowicz

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(2), С. 1232 - 1232

Опубликована: Янв. 8, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic, whereas influenza A virus (IAV) causes seasonal epidemics and occasional pandemics. Both viruses lead to widespread infection death. SARS-CoV-2 are RNA viruses. The genome an approximately 30 kb, positive sense, 5′ capped single-stranded molecule. possesses eight negative-sense segments. secondary structure in untranslated coding regions crucial viral replication cycle. within of has been intensively studied. Because whole cycles dependent on with no DNA intermediate, a natural promising target development inhibitors. There lot RNA-targeting strategies regulating pathogenic RNA, such as small interfering interference, antisense oligonucleotides, catalytic nucleic acids, molecules. In this review, we summarized knowledge about inhibition propagation by targeting their structure.

Язык: Английский

Процитировано

18

Navigating the Complex Landscape of Ebola Infection Treatment: A Review of Emerging Pharmacological Approaches DOI Creative Commons
Francisca Almeida-Pinto, Rui Pinto, João Rocha

и другие.

Infectious Diseases and Therapy, Год журнала: 2024, Номер 13(1), С. 21 - 55

Опубликована: Янв. 1, 2024

In 1976 Ebola revealed itself to the world, marking beginning of a series localized outbreaks. However, it was outbreak that began in 2013 incited fear and anxiety around globe. Since then, our comprehension virus has been steadily expanding. (EBOV), belonging Orthoebolavirus genus Filoviridae family, possesses non-segmented, negative single-stranded RNA genome comprising seven genes encode multiple proteins. These proteins collectively orchestrate intricate process infecting host cells. It is not possible view each protein as monofunctional. Instead, they synergistically contribute pathogenicity virus. Understanding this multifaceted replication cycle crucial for development effective antiviral strategies. Currently, two antibody-based therapeutics have received approval treating disease (EVD). 2022, first evidence-based clinical practice guideline dedicated specific therapies EVD published. Although notable progress made recent years, deaths still occur. Consequently, there an urgent need enhance therapeutic options available improve outcomes disease. Emerging can target viral direct-acting antivirals or factors host-directed antivirals. They both advantages disadvantages. One way bypass some disadvantages repurpose already approved drugs non-EVD indications treat EVD. This review offers detailed insight into role virus, understanding how interacts with cells critical emerging exert their activity. Using knowledge, delves mechanisms action current therapeutics.

Язык: Английский

Процитировано

7