Mechanistic Insights into the Mutational Landscape of the Main Protease/3CLPro and Its Impact on Long-Term COVID-19/SARS-CoV-2 Management DOI Creative Commons
Aganze Gloire-Aimé Mushebenge, Samuel Chima Ugbaja,

Nonjabulo Ntombikhona Magwaza

и другие.

Future Pharmacology, Год журнала: 2024, Номер 4(4), С. 825 - 852

Опубликована: Ноя. 28, 2024

The main proteinase (Mpro), or 3CLpro, is a critical enzyme in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle and responsible for breaking down releasing vital functional viral proteins crucial virus development transmission. As catalytically active dimer, its dimerization interface has become an attractive target antiviral drug development. Recent research extensively investigated enzymatic activity of Mpro, focusing on role regulating replication complex significance maturation infectivity. Computational investigations have identified four druggable pockets, suggesting potential allosteric sites beyond substrate-binding region. Empirical validation through site-directed alanine mutagenesis targeted residues both regions corroborated these predictions. Structural studies can inform therapeutic approaches, with metadynamics simulations shedding light H163 Mpro function providing insights into dynamic equilibrium to wild-type enzyme. Despite efficacy vaccines drugs mitigating SARS-CoV-2 spread, ongoing evolution, selective pressures, continued transmission pose challenges, potentially leading resistant mutations. Phylogenetic analyses indicated existence several variations predating introduction human population, emphasizing likelihood spread. Hydrogen/deuterium-exchange mass spectrometry reveals structural influence mutation. At same time, clinical trials 3CLPro inhibitors underscore reduced offer avenues future exploration. Understanding implications mutations holds promise shaping forthcoming strategies against COVID-19. This review delves factors influencing mutation rates identifies areas warranting further investigation, comprehensive overview mutations, categorization, terminology. Moreover, we examine their associations outcomes, illness severity, unresolved issues, prospects, including impact vaccine targeting.

Язык: Английский

Multiple functions of heterogeneous nuclear ribonucleoproteins in the positive single-stranded RNA virus life cycle DOI Creative Commons
Jingming Wang, Di Sun,

Mingshu Wang

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Сен. 2, 2022

The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a diverse family of RNA binding proteins that implicated in metabolism, such as alternative splicing, mRNA stabilization and translational regulation. According to their different cellular localization, hnRNPs display multiple functions. Most were predominantly located the nucleus, but some them could redistribute cytoplasm during virus infection. HnRNPs consist domains motifs enable these recognize predetermined nucleotide sequences. In virus-host interactions, specifically bind viral or proteins. And protein-hnRNP interactions require other host factors intermediate. Through various mechanisms, regulate translation, genome replication, switch translation replication virion release. This review highlights common features distinguish roles life cycle positive single-stranded viruses.

Язык: Английский

Процитировано

35
New perspective of small-molecule antiviral drugs development for RNA viruses DOI
Shasha Li, Huixia Li,

Ruiya Lian

и другие.

Virology, Год журнала: 2024, Номер 594, С. 110042 - 110042

Опубликована: Март 7, 2024

Язык: Английский

Процитировано

7
Viral strategies to antagonize the host antiviral innate immunity: an indispensable research direction for emerging virus-host interactions DOI Creative Commons

Na Chen,

Jiayu Jin,

Baoge Zhang

и другие.

Emerging Microbes & Infections, Год журнала: 2024, Номер unknown

Опубликована: Июнь 7, 2024

The public's health is gravely at risk due to the current global outbreak of emerging viruses, specifically SARS-CoV-2 and MPXV. Recent studies have shown that mutants (such as Omicron) exhibit a higher capability antagonize host innate immunity, increasing their human adaptability transmissibility. Furthermore, on strategies for MPXV immunity are still in initial stages. These multiple threats from viruses make it urgent study virus-host interactions, especially viral antagonism antiviral immunity. Given this, we selected several representative significantly threatened public interpreted these hoping provide ideas molecular mechanism research accelerate progress. IAV, SARS-CoV-2, SARS-CoV, MERS-CoV, EBOV, DENV, ZIKV, HIV some typical viruses. Studies could by directly or indirectly blocking immune signaling pathways. Proviral factors, restriction ncRNAs (microRNAs, lncRNAs, circRNAs, vtRNAs) essential via controlling apoptosis, ER stress, stress granule formation, metabolic pathways, may it. regulatory mechanisms include transcriptional regulation, post-translational preventing complex impeding nuclear translocation, cleavage, degradation, epigenetic regulation.

Язык: Английский

Процитировано

7
Development and Application of a High-Titer VSV-Based HCoV-NL63 Pseudovirus System via C-terminal 14 amino acid Truncation of Spike DOI
Liting Shao, Mingming Wang, Yiming Wang

и другие.

Biochemical and Biophysical Research Communications, Год журнала: 2025, Номер unknown, С. 151458 - 151458

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Roles of p53-Mediated Host–Virus Interaction in Coronavirus Infection DOI Open Access
Xue Wang, Yi Liu, Kaiyuan Li

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(7), С. 6371 - 6371

Опубликована: Март 28, 2023

The emergence of the SARS-CoV-2 coronavirus has garnered global attention due to its highly pathogenic nature and resulting health crisis economic burden. Although drugs such as Remdesivir have been considered a potential cure by targeting virus on RNA polymerase, high mutation rate unique 3' 5' exonuclease with proofreading function make it challenging develop effective anti-coronavirus drugs. As result, there is an increasing focus host-virus interactions because coronaviruses trigger stress responses, cell cycle changes, apoptosis, autophagy, dysregulation immune inflammation in host cells. p53 tumor suppressor molecule critical regulator signaling pathways, cellular DNA repair, apoptosis. However, viruses can activate or inhibit during viral infections enhance replication spread. Given pivotal role physiology, represents target for This review aims summarize relationship between from various perspectives, shed light targets antiviral drug development vaccine design.

Язык: Английский

Процитировано

12
A pan-respiratory antiviral chemotype targeting a transient host multi-protein complex DOI Creative Commons
Maya Michon, Andreas Müller‐Schiffmann,

Anuradha F. Lingappa

и другие.

Open Biology, Год журнала: 2024, Номер 14(6)

Опубликована: Июнь 1, 2024

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity PAV-431, representative compound from the series, has been validated against infectious viruses in multiple cell culture models all six families causing most respiratory diseases humans. In animals, this demonstrated efficacious porcine epidemic diarrhoea virus (a coronavirus) syncytial paramyxovirus). PAV-431 is shown to bind 14-3-3, known allosteric modulator. However, it only appears target subset 14-3-3 which dynamic multi-protein complex whose components include proteins implicated life cycles innate immunity. The composition be modified upon infection largely restored treatment. An advanced analog, PAV-104, selective virally target, thereby avoiding host toxicity. Our findings suggest new paradigm understanding, drugging, host–virus interface, leads clinical therapeutic strategy treatment disease.

Язык: Английский

Процитировано

4
The Strategies Used by Animal Viruses to Antagonize Host Antiviral Innate Immunity: New Clues for Developing Live Attenuated Vaccines (LAVs) DOI Creative Commons
Na Chen,

Baoge Zhang

Vaccines, Год журнала: 2025, Номер 13(1), С. 46 - 46

Опубликована: Янв. 8, 2025

As an essential type of vaccine, live attenuated vaccines (LAVs) play a crucial role in animal disease prevention and control. Nevertheless, developing LAVs faces the challenge balancing safety efficacy. Understanding mechanisms viruses use to antagonize host antiviral innate immunity may help precisely regulate vaccine strains maintain strong immunogenicity while reducing their pathogenicity. It improve efficacy LAVs, as well provide more reliable means for control infectious livestock diseases. Therefore, exploring viral antagonistic is significant clue which helps explore virulence factors (as new targets) provides vital theoretical basis technical support development. Among viruses, ASFV, PRRSV, PRV, CSFV, FMDV, PCV, PPV, AIV are some typical representatives. conduct in-depth research summarize strategies these viruses. Studies have indicated that by directly or indirectly blocking signaling pathways. In addition, also do this antagonizing restriction targeting replication cycle. Beyond that, via regulating apoptosis, metabolic pathways, stress granule formation. A summary might understanding pathogenic mechanism based on factors.

Язык: Английский

Процитировано

0
Insights into Virus-Host Interactions: Lessons from Caenorhabditis elegans-Orsay Virus Model DOI

Xin Wu,

Heng Liu, Yusong R. Guo

и другие.

Current Medical Science, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Язык: Английский

Процитировано

0
Structural Virology: The Key Determinants in Development of Antiviral Therapeutics DOI Creative Commons
Tanuj Handa, Ankita Saha, Aarthi Narayanan

и другие.

Viruses, Год журнала: 2025, Номер 17(3), С. 417 - 417

Опубликована: Март 14, 2025

Structural virology has emerged as the foundation for development of effective antiviral therapeutics. It is pivotal in providing crucial insights into three-dimensional frame viruses and viral proteins at atomic-level or near-atomic-level resolution. Structure-based assessment components, including capsids, envelope proteins, replication machinery, host interaction interfaces, instrumental unraveling multiplex mechanisms infection, replication, pathogenesis. The structural elucidation enzymes, proteases, polymerases, integrases, been essential combating like HIV-1 HIV-2, SARS-CoV-2, influenza. Techniques X-ray crystallography, Nuclear Magnetic Resonance spectroscopy, Cryo-electron Microscopy, Tomography have revolutionized field significantly aided discovery ubiquity chronic infections, along with emergence reemergence new threats necessitate novel strategies agents, while extensive diversity their high mutation rates further underscore critical need analysis to aid development. This review highlights significance structure-based investigations bridging gap between structure function, thus facilitating therapeutics, vaccines, antibodies tackling emerging threats.

Язык: Английский

Процитировано

0
EXOC8 of Epinephelus coioides involved in SGIV infection via Innate Immunity and Apoptosis DOI
Wei Huang, Zi-An Chen,

Q. Li

и другие.

Developmental & Comparative Immunology, Год журнала: 2025, Номер unknown, С. 105368 - 105368

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0