Developing a SARS-CoV-2 main protease binding prediction random forest model for drug repurposing for COVID-19 treatment DOI Open Access
Jie Liu, Liang Xu, Wenjing Guo

et al.

Experimental Biology and Medicine, Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 24, 2023

The coronavirus disease 2019 (COVID-19) global pandemic resulted in millions of people becoming infected with the severe acute respiratory syndrome 2 (SARS-CoV-2) virus and close to seven million deaths worldwide. It is essential further explore design effective COVID-19 treatment drugs that target main protease SARS-CoV-2, a major for drugs. In this study, machine learning was applied predicting SARS-CoV-2 binding Food Drug Administration (FDA)-approved assist identification potential repurposing candidates treatment. Ligands bound Protein Data Bank compounds experimentally tested assays literature were curated. These chemicals divided into training (516 chemicals) testing (360 data sets. To identify binders as treat COVID-19, 1188 FDA-approved from Liver Toxicity Knowledge Base obtained. A random forest algorithm used constructing predictive models based on molecular descriptors calculated using Mold2 software. Model performance evaluated 100 iterations fivefold cross-validations which 78.8% balanced accuracy. model constructed whole dataset predict set applicability domain prediction confidence predicted discovered 10 COVID-19. Our results demonstrate an efficient method drug and, thus, may accelerate development targeting SARS-CoV-2.

Language: Английский

Potential Resistance of SARS-CoV-2 Main Protease (Mpro) against Protease Inhibitors: Lessons Learned from HIV-1 Protease DOI Open Access
János András Mótyán, Mohamed Mahdi, Gyula Hoffka

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3507 - 3507

Published: March 23, 2022

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome 2 (SARS-CoV-2), has been one of most devastating pandemics recent times. The lack potent novel antivirals had led to global health crises; however, emergence and approval inhibitors viral main protease (Mpro), such as Pfizer’s newly approved nirmatrelvir, offers hope not only in therapeutic front but also context prophylaxis against infection. By their nature, RNA viruses including human immunodeficiency virus (HIV) have inherently high mutation rates, lessons learnt from previous currently ongoing taught us that these can easily escape selection pressure through vital target amino acid residues monotherapeutic settings. In this paper, we review nirmatrelvir its binding SARS-CoV-2 Mpro draw a comparison HIV were rendered obsolete resistance mutations, emphasizing potential pitfalls design may be important relevance long-term use SARS-CoV-2.

Language: Английский

Citations

63
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

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1232 - 1232

Published: Jan. 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.

Language: Английский

Citations

18
Omicron Coronavirus: pH-Dependent Electrostatic Potential and Energy of Association of Spike Protein to ACE2 Receptor DOI Creative Commons
S. Hristova, Alexandar M. Zhivkov

Viruses, Journal Year: 2023, Volume and Issue: 15(8), P. 1752 - 1752

Published: Aug. 17, 2023

The association of the S-protein SARS-CoV-2 beta coronavirus to ACE2 receptors human epithelial cells determines its contagiousness and pathogenicity. We computed pH-dependent electric potential on surface interacting globular proteins Gibbs free energy at wild-type strain omicron variant. calculated isoelectric points receptor (pI 5.4) in trimeric form 7.3, wild type), 7.8, variant), experimentally verified by focusing, show that pH 6-7, S1-ACE2 is conditioned electrostatic attraction oppositely charged viral protein. comparison local potentials variant shows point mutations alter a relatively small area receptor-binding domain (RBD) S1 subunit. appearance seven charge-changing RBD (equivalent three additional positive charges) leads stronger 5.5 (typical for respiratory tract) weaker one 7.4 (characteristic blood plasma); this reveals reason higher but lower pathogenicity strain.

Language: Английский

Citations

18
Computational screening combined with well-tempered metadynamics simulations identifies potential TMPRSS2 inhibitors DOI Creative Commons

C. S. Sharanya,

D. Sasikala Wilbee,

Shijulal Nelson‐Sathi

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 13, 2024

Abstract Type-II transmembrane serine proteases are effective pharmacological targets for host defence against viral entry and in certain cancer cell progressions. These cleave spike proteins to expose the fusion peptide entry, which is essential life cycle of virus. TMPRSS2 inhibitors can also fight respiratory viruses that employ them entry. Our study combining virtual screening, all-atom molecular dynamics, well-tempered metadynamics simulation identifies vicenin-2, neohesperidin, naringin, rhoifolin as promising antagonists. The binding energies obtained − 16.3, 15.4, 13.6, 13.8 kcal/mol respectively. RMSD, RMSF, PCA, DCCM, free energy profiles correlate with stable these ligands at active site TMPRSS2. reveals molecules could be lead combating future outbreaks coronavirus other viruses.

Language: Английский

Citations

8
Optical biosensors for diagnosis of COVID-19: nanomaterial-enabled particle strategies for post pandemic era DOI Creative Commons

Yusuf Şamil Tekin,

Seyda Mihriban Kul,

Osman Sağdıç

et al.

Microchimica Acta, Journal Year: 2024, Volume and Issue: 191(6)

Published: May 10, 2024

Abstract The COVID-19 pandemic underlines the need for effective strategies controlling virus spread and ensuring sensitive detection of SARS-CoV-2. This review presents potential nanomaterial-enabled optical biosensors rapid low-cost SARS-CoV-2 biomarkers, demonstrating a comprehensive analysis including colorimetric, fluorescence, surface-enhanced Raman scattering, surface plasmon resonance methods. Nanomaterials metal-based nanomaterials, metal–organic frame–based nanoparticles, nanorods, nanoporous materials, nanoshell magnetic nanoparticles employed in production are presented detail. also discusses principles, fabrication methods, nanomaterial synthesis, their applications four categories: antibody-based, antigen-based, nucleic acid–based, aptamer-based biosensors. critical includes reports published literature between years 2021 2024. In addition, offers insights into nanobiosensors diagnosis COVID-19. integration artificial intelligence machine learning technologies with is proposed to improve efficiency diagnostic systems future scenarios. Graphical

Language: Английский

Citations

7
Unveiling the Potential: High-Affinity aptamers for point of care detection of SARS-CoV-2 RBD protein and it’s validation in clinical samples DOI

Narlawar Sagar Shrikrishna,

Sayanti Halder,

Veerbhan Kesarwani

et al.

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 493, P. 152841 - 152841

Published: June 5, 2024

Language: Английский

Citations

7
Nanomolar anti-SARS-CoV-2 Omicron activity of the host-directed TMPRSS2 inhibitor N-0385 and synergistic action with direct-acting antivirals DOI Creative Commons
Jimena Pérez‐Vargas, Gabriel Lemieux,

Connor A.H. Thompson

et al.

Antiviral Research, Journal Year: 2024, Volume and Issue: 225, P. 105869 - 105869

Published: March 26, 2024

SARS-CoV-2 Omicron subvariants with increased transmissibility and immune evasion are spreading globally alarming persistence. Whether the mutations evolution of spike (S) alter viral hijacking human TMPRSS2 for entry remains to be elucidated. This is particularly important investigate because large number diversity S reported since emergence BA.1. Here we report that a molecular determinant all clinical isolates tested in lung cells, including ancestral (BA.1, BA.2, BA.5), contemporary (BQ.1.1, XBB.1.5, EG.5.1) currently circulating BA.2.86. First, used co-transfection assay demonstrate endoproteolytic cleavage by subvariants. Second, found N-0385, highly potent inhibitor, robust inhibitor virus-like particles harbouring protein Third, show N-0385 exhibits nanomolar broad-spectrum antiviral activity against live Calu-3 cells primary patient-derived bronchial epithelial cells. Interestingly, 10-20 times more than repositioned camostat, BA.5, EG.5.1, We further shows broad synergistic clinically approved direct-acting antivirals (DAAs), i.e., remdesivir nirmatrelvir, subvariants, demonstrating potential therapeutic benefits multi-targeted treatment based on DAAs.

Language: Английский

Citations

6
Optimized production and fluorescent labeling of SARS-CoV-2 virus-like particles DOI Creative Commons

Manon Gourdelier,

Jitendriya Swain, Coline Arone

et al.

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Aug. 27, 2022

SARS-CoV-2 is an RNA enveloped virus responsible for the COVID-19 pandemic that conducted in 6 million deaths worldwide so far. particles are mainly composed of 4 main structural proteins M, N, E and S to form 100 nm diameter viral particles. Based on productive assays, we propose optimal transfected plasmid ratio mimicking infected cells. This allows Virus-Like Particle (VLPs) formation mature S. Furthermore, fluorescent or photoconvertible VLPs were generated by adding a protein tag N M mixing with unlabeled characterized western blots, atomic force microscopy coupled fluorescence immuno-spotting. Thanks live super-resolution microscopies, quantified size concentration. present 110 140 respectively MNE-VLPs MNES-VLPs concentration 10e12 VLP/ml. In this condition, able establish incorporation Spike VLPs. Finally, functionality was assessed monitoring docking internalization human pulmonary cells expressing not receptor hACE2. Results show preferential maturation N(GFP) labeled hACE2-dependent VLP potential fusion host work provides new insights use non-fluorescent study visualize life cycle safe environment (BSL-2 instead BSL-3). Moreover, optimized production can be further adapted vaccine design strategies.

Language: Английский

Citations

28
An exhaustive comprehension of the role of herbal medicines in Pre- and Post-COVID manifestations DOI
Shiv Kumar Prajapati, Akanksha Malaiya, Gaurav Mishra

et al.

Journal of Ethnopharmacology, Journal Year: 2022, Volume and Issue: 296, P. 115420 - 115420

Published: May 31, 2022

Language: Английский

Citations

27
Engineered mRNA Delivery Systems for Biomedical Applications DOI
Ji Wang,

Haofang Zhu,

Jingjing Gan

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(15)

Published: Oct. 9, 2023

Messenger RNA (mRNA)-based therapeutic strategies have shown remarkable promise in preventing and treating a staggering range of diseases. Optimizing the structure delivery system engineered mRNA has greatly improved its stability, immunogenicity, protein expression levels, which led to wider uses for therapeutics. Herein, thorough analysis optimization used is first provided systems are described great detail. Furthermore, latest advancements biomedical engineering technology, including applications combatting infectious diseases, cancer, providing replacement therapy, conducting gene editing, more, summarized. Lastly, perspective on forthcoming challenges prospects concerning advancement therapeutics offered. Despite these challenges, mRNA-based remain promising, with potential revolutionize disease treatment contribute significant field.

Language: Английский

Citations

14