In Silico Screening of Potential Antiviral Inhibitors against SARS-CoV-2 Main Protease DOI Creative Commons
Kandhan Palanisamy, K. Rudharachari Maiyelvaganan, Shanmugasundaram Kamalakannan

et al.

Research Square (Research Square), Journal Year: 2022, Volume and Issue: unknown

Published: March 24, 2022

Abstract Respiratory illness due to SARS-CoV-2 emerged in 2019 and has a significant morbidity mortality rate. The main protease (Mpro) is mainly responsible for the viral replications, which acts as good drug target inhibit related diseases. Chemical compounds obtained from various herbal plants are showing potent antiviral activity against numerous Initial screening was performed with phytochemicals Mpro using molecular docking. These result shows that there strong interaction exhibited between active sites ( His-41 Cys-145 ) of chemical compounds. In addition, ADME prediction Lipinski’s rule five calculations demonstrated selected have potential drug-like properties. Further, dynamics (MD) simulations were understand stability structural changes protein-ligand complexes top MM/PBSA studies strongly suggested sitosterol, spinasterol, asarinin form stable . most hot spot residues such Thr-25, Met-49, Cys-145, Met-165, Gln-189 interacted Our suggest best inhibitor Mpro, supports these candidates could be agents SARS-CoV-2.

Language: Английский

Ionic Liquid Coating‐Driven Nanoparticle Delivery to the Brain: Applications for NeuroHIV DOI
Christine M. Hamadani, Fakhri Mahdi,

Anya Merrell

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: April 4, 2024

Abstract Delivering cargo to the central nervous system (CNS) remains a pharmacological challenge. For infectious diseases such as HIV, CNS acts latent reservoir that is inadequately managed by systemic antiretrovirals (ARTs). ARTs thus cannot eradicate and given infection, patients experience neurological deficits collectively referred “neuroHIV”. Herein, development of bioinspired ionic liquid‐coated nanoparticles (IL‐NPs) for in situ hitchhiking on red blood cells (RBCs) reported, which enables 48% brain delivery intracarotid arterial‐ infused cargo. Moreover, IL choline trans‐2‐hexenoate (CA2HA 1:2) demonstrates preferential accumulation parenchymal microglia over endothelial post‐delivery. This study further successful loading abacavir (ABC), an ART challenging encapsulate, into IL‐NPs, verifies retention antiviral efficacy vitro. IL‐NPs are not cytotoxic primary human peripheral mononuclear (PBMCs) CA2HA 1:2 coating itself confers notable anti‐viremic capacity. In addition, vitro cell culture assays show markedly increased uptake neural compared bare PLGA nanoparticles. work debuts liquids promising nanoparticle coatings assist biodistribution has potential revolutionize cargos (i.e., drugs, viral vectors) through compartmental barriers blood‐brain‐barrier (BBB).

Language: Английский

Citations

7
Bioprospecting phytochemicals of Rosmarinus officinalis L. for targeting SARS-CoV-2 main protease (Mpro): a computational study DOI Open Access
Unnati P. Patel,

Krishna Desai,

Ranjitsinh C. Dabhi

et al.

Journal of Molecular Modeling, Journal Year: 2023, Volume and Issue: 29(5)

Published: April 28, 2023

Language: Английский

Citations

14
In-silico study for the screening and preparation of ionic liquid-AVDs conjugate to combat COVID-19 surge DOI

Juhi Saraswat,

Ufana Riaz, Rajan Patel

et al.

Journal of Molecular Liquids, Journal Year: 2022, Volume and Issue: 359, P. 119277 - 119277

Published: May 3, 2022

Language: Английский

Citations

12
Effect of mixtures of ionic liquids and water on the structure and stability of the insulin dimer: a combined DFT and MD simulation study DOI
N. Giri Lakshman, S. M. Esther Rubavathy, Sridhar Priyankha

et al.

New Journal of Chemistry, Journal Year: 2023, Volume and Issue: 47(26), P. 12152 - 12163

Published: Jan. 1, 2023

The role of water and water-mediated H-bonding interactions on the stability insulin dimer in binary mixtures ILs is studied.

Language: Английский

Citations

3
Counteractive Effects of Choline Geranate (CAGE) ILs and Ethanol on Insulin’s Stability—A Leap Forward towards Oral Insulin Formulation DOI Creative Commons
Kandhan Palanisamy, Muthuramalingam Prakash

Molecules, Journal Year: 2022, Volume and Issue: 27(15), P. 5031 - 5031

Published: Aug. 8, 2022

Choline geranate (CAGE) ionic liquids (ILs) stabilize insulin, thereby aiding its oral delivery, whereas ethanol (EtOH) affects stability by disrupting the hydrophobic interactions. In this study, cognizance of stabilization mechanism insulin dimer in presence both CAGE ILs and EtOH mixtures is achieved through biased unbiased molecular dynamics (MD) simulations. Here, two order parameters are employed to study dissociation using well-tempered metadynamics (WT-MetaD). The found be strongly maintained until a 0.20 mole fraction EtOH. Besides, higher concentrations marginally affect stability. Moreover, anions form number H-bonding interactions with water molecules, which aids stabilization. Conversely, addition minimizes water-mediated geranate. Additionally, traps preventing between Furthermore, free energy landscape (FEL) reveals absence along noticeable deviations distances R contacts Q. dimerization was calculated -16.1 kcal/mol at increments fractions effectuate decrease Thus, present represents as efficient stabilizes low

Language: Английский

Citations

5
Chemical Attachment of 5-Nitrosalicylaldimine Motif to Silatrane Resulting in an Organic–Inorganic Structure with High Medicinal Significance DOI Creative Commons
Mirela‐Fernanda Zaltariov, Mihaela Turtoi, Dragos Peptanariu

et al.

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(12), P. 2838 - 2838

Published: Dec. 18, 2022

Two chemical motifs of interest for medicinal chemistry, silatrane as 1-(3-aminopropyl) (SIL M), and nitro group attached in position 5 to salicylaldehyde, are coupled a new structure, 1-(3-{[(2-hydroxy-5-nitrophenyl)methylidene]amino}propyl)silatrane (SIL-BS), through an azomethine moiety, also known versatile pharmacophore. The high purity isolated compound was structurally characterized by elemental, spectral, single crystal X-ray diffraction analysis. Given the structural premises being biologically active compound, different specific techniques protocols have been used evaluate their vitro hydrolytic stability simulated physiological conditions, cytotoxicity on two cancer cell lines (HepG2 MCF7), protein binding ability—with major role drug ADME (Absorption, Distribution, Metabolism Excretion), parallel with those SIL M. While latter had good biocompatibility, nitro-silatrane derivative, SIL-BS, exhibited higher cytotoxic activity HepG2 MCF7 lines, performance assigned, among others, capacity promote “activation reduction” mechanism. Both compounds increased bio- muco-adhesiveness, which can favor optimized therapeutic effect permeation residence time tumor location. Additional benefits these demonstrated antimicrobial several fungi bacteria species. Molecular docking computations Human Serum Albumin (HSA) MPRO COVID-19 protease potential development drugs combined therapy.

Language: Английский

Citations

5
Ionic Liquid Coating-Driven Nanoparticle Delivery to the Brain: Applications for NeuroHIV DOI Creative Commons
Christine M. Hamadani, Fakhri Mahdi,

Anya Merrell

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 14, 2023

Delivering cargo to the central nervous system (CNS) remains a pharmacological challenge. For infectious diseases such as HIV, CNS acts latent reservoir that is inadequately managed by systemic antiretrovirals (ARTs). ARTs thus cannot eradicate and given infection, patients experience an array of neurological deficits are collectively referred 'neuroHIV'. Herein we report development bioinspired ionic liquid-coated nanoparticles (IL-NPs) for

Language: Английский

Citations

2
Bridging the Gap: Can COVID-19 Research Help Combat African Swine Fever? DOI Creative Commons
Danaya Pakotiprapha, Sakonwan Kuhaudomlarp,

Ruchanok Tinikul

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(9), P. 1925 - 1925

Published: Sept. 15, 2023

African swine fever (ASF) is a highly contagious and economically devastating disease affecting domestic pigs wild boar, caused by virus (ASFV). Despite being harmless to humans, ASF poses significant challenges the industry, due sudden losses trade restrictions. The ongoing COVID-19 pandemic has spurred an unparalleled global research effort, yielding remarkable advancements across scientific disciplines. In this review, we explore potential technological spillover from into ASF. Specifically, assess applicability of diagnostic tools, vaccine development strategies, biosecurity measures developed for combating Additionally, discuss lessons learned in terms surveillance systems their implications managing By bridging gap between research, highlight interdisciplinary collaboration spillovers battle against

Language: Английский

Citations

2
Computational Approaches to Designing Antiviral Drugs against COVID-19: A Comprehensive Review DOI
Mohan Singh, Nidhi Singh,

Divya Mishra

et al.

Current Pharmaceutical Design, Journal Year: 2023, Volume and Issue: 29(33), P. 2601 - 2617

Published: Sept. 1, 2023

Abstract: The global impact of the COVID-19 pandemic caused by SARS-CoV-2 necessitates innovative strategies for rapid development effective treatments. Computational methodologies, such as molecular modelling, dynamics simulations, and artificial intelligence, have emerged indispensable tools in drug discovery process. This review aimed to provide a comprehensive overview these computational approaches their application design antiviral agents COVID-19. Starting with an examination ligand-based structure-based discovery, has delved into intricate ways through which modelling can accelerate identification potential therapies. Additionally, investigation extends phytochemicals sourced from nature, shown promise agents. Noteworthy compounds, including gallic acid, naringin, hesperidin, Tinospora cordifolia, curcumin, nimbin, azadironic nimbionone, nimbionol, nimocinol, exhibited high affinity Mpro favourable binding energy profiles compared current drugs. Although compounds hold potential, further validation vitro vivo experimentation is imperative. Throughout this exploration, emphasized pivotal role biologists, bioinformaticians, biotechnologists driving advancements clinical research therapeutic development. By combining state-of-the-art techniques insights structural biology, search potent been accelerated. collaboration between disciplines holds immense addressing transmissibility virulence SARS-CoV-2.

Language: Английский

Citations

2
Discovery of novel HDAC8 inhibitors from natural compounds by in silico high throughput screening DOI
S. M. Esther Rubavathy, Kandhan Palanisamy, Sridhar Priyankha

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2022, Volume and Issue: 41(19), P. 9492 - 9502

Published: Nov. 12, 2022

A class I histone deacetylase HDAC8 is associated with several diseases, including cancer, intellectual impairment and parasite infection. Most of the HDAC inhibitors that have so far been found to inhibit limit their efficacy in clinic by producing toxicities. It therefore very desirable develop specific inhibitors. The emergence derived from natural sources has become quite popular. In recent decades, it shown naturally occurring strong anticancer properties. total 0.2 million compounds were screened against Universal Natural Product Database (UNPD). Molecular docking was performed for these top six hits obtained. addition, molecular dynamics (MD) simulations used evaluate structural stability binding affinity inhibitors, which showed protein-ligand complexes remained stable throughout 100 ns simulation. MM-PBSA method demonstrated selected high towards HDAC8. We infer our findings Hit-1 (-29.35 kcal mol-1), Hit-2 (-29.15 mol-1) Hit-6 (-30.28 better adhesion ADMET (absorption, distribution, metabolism, excretion toxicity) characteristics To compare discussions result an effective way. docking, MD analysis FDA-approved drug romidepsin. above results show than compound romidepsin (-12.03 ± 4.66 mol-1). important hotspot residues Asp29, Ile34, Trp141, Phe152, Asp267, Met274 Tyr306 significantly contributed interaction. These suggest vitro testing additional optimization may lead development inhibitors.Communicated Ramaswamy H. Sarma.

Language: Английский

Citations

3