The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach DOI Open Access
Luisa Di Paola, Hamid Hadi‐Alijanvand, Xingyu Song

et al.

Journal of Proteome Research, Journal Year: 2020, Volume and Issue: 19(11), P. 4576 - 4586

Published: June 17, 2020

SARS-CoV-2 has caused the largest pandemic of twenty-first century (COVID-19), threatening life and economy all countries in world. The identification novel therapies vaccines that can mitigate or control this global health threat is among most important challenges facing biomedical sciences. To construct a long-term strategy to fight both other possible future threats from coronaviruses, it critical understand molecular mechanisms underlying virus action. viral entry associated infectivity stems formation spike protein complex with angiotensin-converting enzyme 2 (ACE2). detection putative allosteric sites on molecule be used elucidate pathways targeted drugs weaken spike-ACE2 interaction and, thus, reduce infectivity. In study, we present results application different computational methods aimed at detecting protein. adopted tools consisted contact networks (PCNs), SEPAS (Affinity by Flexibility), perturbation response scanning (PRS) based elastic network modes. All these were applied ACE2 SARS-CoV2 SARS-CoV proteins. analyses converged toward specific region (allosteric modulation [AMR]), complexes predicted act as an site modulating binding ACE2. Preliminary hepcidin (a strong structural sequence AMR) indicated inhibitory effect affinity

Language: Английский

Notch signaling pathway in cancer: from mechanistic insights to targeted therapies DOI Creative Commons

Qingmiao Shi,

Chen Xue,

Yifan Zeng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 27, 2024

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The receptor ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical signaling transduction. Accumulating evidence indicates that the pathway serves as both an oncogenic factor a tumor suppressor various cancer types. Dysregulation of this promotes epithelial-mesenchymal transition angiogenesis malignancies, closely linked proliferation, invasion, metastasis. Furthermore, contributes maintaining stem-like properties cells, thereby enhancing invasiveness. regulatory metabolic reprogramming microenvironment suggests pivotal involvement balancing suppressive effects. Moreover, implicated conferring chemoresistance cells. Therefore, comprehensive understanding these biological processes crucial developing innovative therapeutic strategies targeting signaling. This review focuses on research progress cancers, providing in-depth insights into potential mechanisms regulation occurrence progression cancer. Additionally, summarizes pharmaceutical clinical trials therapy, aiming offer new human malignancies.

Language: Английский

Citations

84
Ultrasensitive and Specific Clustered Regularly Interspaced Short Palindromic Repeats Empowered a Plasmonic Fiber Tip System for Amplification-Free Monkeypox Virus Detection and Genotyping DOI Creative Commons
Yuzhi Chen, Zhi Chen, Tianzhong Li

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(13), P. 12903 - 12914

Published: June 29, 2023

The urgent necessity for highly sensitive diagnostic tools has been accentuated by the ongoing mpox (monkeypox) virus pandemic due to complexity in identifying asymptomatic and presymptomatic carriers. Traditional polymerase chain reaction-based tests, despite their effectiveness, are hampered limited specificity, expensive bulky equipment, labor-intensive operations, time-consuming procedures. In this study, we present a clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a-based platform with surface plasmon resonance-based fiber tip (CRISPR-SPR-FT) biosensor. compact CRISPR-SPR-FT biosensor, 125 μm diameter, offers high stability portability, enabling exceptional specificity diagnosis precise identification of samples fatal mutation site (L108F)

Language: Английский

Citations

50
Facile biosensors for rapid detection of COVID-19 DOI Open Access
Lizhou Xu, Danyang Li,

Sami Ramadan

et al.

Biosensors and Bioelectronics, Journal Year: 2020, Volume and Issue: 170, P. 112673 - 112673

Published: Oct. 1, 2020

Language: Английский

Citations

124
Genetic comparison among various coronavirus strains for the identification of potential vaccine targets of SARS-CoV2 DOI Open Access

Navpreet Kaur,

Rimaljot Singh,

Zahid Dar

et al.

Infection Genetics and Evolution, Journal Year: 2020, Volume and Issue: 89, P. 104490 - 104490

Published: Aug. 1, 2020

Language: Английский

Citations

106
An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors DOI Creative Commons
Alfonso Trezza, Daniele Iovinelli, Annalisa Santucci

et al.

Scientific Reports, Journal Year: 2020, Volume and Issue: 10(1)

Published: Aug. 17, 2020

Abstract The Coronavirus disease 2019 (COVID-19) is an infectious caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). virus has rapidly spread in humans, causing ongoing pandemic. Recent studies have shown that, similarly to SARS-CoV, SARS-CoV-2 utilises Spike glycoprotein on envelope recognise and bind human receptor ACE2. This event initiates fusion of viral host cell membranes then entry into cell. Despite several clinical studies, there are currently no approved vaccines or drugs that specifically target SARS-CoV-2. Until effective vaccine available, repurposing FDA could significantly shorten time reduce cost compared de novo drug discovery. In this study we attempted overcome limitation silico virtual screening applying a robust strategy. We combined integrated docking simulations, with molecular dynamics (MD), Supervised MD (SuMD) Steered (SMD) simulations identify protein – ACE2 interaction inhibitor. Our data showed Simeprevir Lumacaftor receptor-binding domain high affinity prevent interaction.

Language: Английский

Citations

102
Alveolar epithelial cell type II as main target of SARS-CoV-2 virus and COVID-19 development via NF-Kb pathway deregulation: A physio-pathological theory DOI Open Access
Maurizio Carcaterra, C. Caruso

Medical Hypotheses, Journal Year: 2020, Volume and Issue: 146, P. 110412 - 110412

Published: Nov. 23, 2020

Language: Английский

Citations

99
Identification of potential plant bioactive as SARS-CoV-2 Spike protein and human ACE2 fusion inhibitors DOI Open Access
Rahul Singh, Vijay Kumar Bhardwaj, Jatin Sharma

et al.

Computers in Biology and Medicine, Journal Year: 2021, Volume and Issue: 136, P. 104631 - 104631

Published: July 8, 2021

Language: Английский

Citations

96
Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach DOI Open Access
Syed Mohammad Lokman, Md. Rasheduzzaman, Asma Salauddin

et al.

Infection Genetics and Evolution, Journal Year: 2020, Volume and Issue: 84, P. 104389 - 104389

Published: June 2, 2020

Language: Английский

Citations

93
The role of non‐coding RNAs in drug resistance of oral squamous cell carcinoma and therapeutic potential DOI Creative Commons
Xiang Meng,

Qiuyue Lou,

Wenying Yang

et al.

Cancer Communications, Journal Year: 2021, Volume and Issue: 41(10), P. 981 - 1006

Published: July 20, 2021

Oral squamous cell carcinoma (OSCC), the eighth most prevalent cancer in world, arises from interaction of multiple factors including tobacco, alcohol consumption, and betel quid. Chemotherapeutic agents such as cisplatin, 5-fluorouracil, paclitaxel have now become first-line options for OSCC patients. Nevertheless, patients eventually acquire drug resistance, leading to poor prognosis. With discovery identification non-coding RNAs (ncRNAs), functions dysregulated ncRNAs development resistance are gradually being widely recognized. The mechanisms intricate involve efflux, epithelial-mesenchymal transition, DNA damage repair, autophagy. At present, strategies explore reversal need be urgently developed. Nano-delivery self-cellular delivery platforms considered effective overcome due their tumor targeting, controlled release, consistent pharmacokinetic profiles. In particular, combined application new technologies (including CRISPR systems) opened up horizons treatment OSCC. Hence, this review explored emerging regulatory OSCC, elucidated ncRNA-meditated discussed potential value using nanoparticles self-cells carriers

Language: Английский

Citations

89
Antiviral Peptides as Promising Therapeutics against SARS-CoV-2 DOI Creative Commons
Surid Mohammad Chowdhury, Shafi Ahmad Talukder, Akib Mahmud Khan

et al.

The Journal of Physical Chemistry B, Journal Year: 2020, Volume and Issue: 124(44), P. 9785 - 9792

Published: Oct. 23, 2020

Over 50 peptides, which were known to inhibit SARS-CoV-1, computationally screened against the receptor-binding domain (RBD) of spike protein SARS-CoV-2. Based on binding affinity and interaction, 15 peptides selected, showed higher compared α-helix human ACE2 receptor. Molecular dynamics simulation demonstrated that two S2P25 S2P26, most promising candidates, could potentially block entry Tyr489 Tyr505 residues present in "finger-like" projections RBD found be critical for peptide interaction. Hydrogen bonding hydrophobic interactions played important roles prompting peptide-protein Structure-activity relationship indicated containing aromatic (Tyr Phe), nonpolar (Pro, Gly, Leu, Ala), polar (Asn, Gln, Cys) significant contributors. These findings can facilitate rational design selective inhibitors targeting

Language: Английский

Citations

85