Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3′-Processing Suppression DOI Creative Commons
Sharif Karim Sayyed, Marzuqa Quraishi,

D. S. Prabakaran

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 18(1), P. 30 - 30

Published: Dec. 29, 2024

Background: The global AIDS pandemic highlights the urgent need for novel antiretroviral therapies (ART). In our previous work, Zinc C295 was identified as a potent HIV-1 integrase strand transfer (ST) inhibitor. This study explores its potential to also inhibit 3′-processing (3′P), thereby establishing dual-targeting capability. Methods: inhibitory activity of against 3′P evaluated using modified in vitro assay adapted from earlier ST inhibition studies. Molecular docking and molecular dynamics simulations were employed analyse C295’s interactions with allosteric site integrase. Results: demonstrated significant assays (IC50 = 4.709 ± 0.97 µM). Computational analyses revealed key within enzyme’s site, providing insights into dual mechanism. Conclusions: establishes it promising candidate next-generation ART. Its dual-action mechanism may offer advantages enhancing treatment efficacy addressing drug resistance. Further studies are warranted evaluate therapeutic clinical settings.

Language: Английский

Structure based screening and molecular docking with dynamic simulation of natural secondary metabolites to target RNA-dependent RNA polymerase of five different retroviruses DOI Creative Commons
Muhammad Azeem, Ghulam Mustafa, Sibtain Ahmed

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(8), P. e0307615 - e0307615

Published: Aug. 5, 2024

Viral diseases pose a serious global health threat due to their rapid transmission and widespread impact. The RNA-dependent RNA polymerase (RdRp) participates in the synthesis, transcription, replication of viral host. current study investigates antiviral potential secondary metabolites particularly those derived from bacteria, fungi, plants develop novel medicines. Using virtual screening approach that combines molecular docking dynamics (MD) simulations, we aimed discover compounds with strong interactions RdRp five different retroviruses. top were selected for each based on scores, binding patterns, interactions, drug-likeness properties. uncovered several activity against RdRp. For instance, cytochalasin Z8 had lowest score -8.9 (kcal/mol) SARS-CoV-2, aspulvinone D (-9.2 kcal/mol) HIV-1, talaromyolide (-9.9 hepatitis C, Ebola also maintained -9.2 kcal/mol enzyme dengue virus. These showed remarkable comparable standard drug (remdesivir -7.4 approved target possess no significant toxicity. simulation confirmed best ligands firmly bound respective proteins time 200 ns. identified lead distinctive pharmacological characteristics, making them candidates repurposing as drugs SARS-CoV-2. Further experimental evaluation investigation are recommended ascertain efficacy potential.

Language: Английский

Citations

3
Augmenting phyto-chemical and phyto-mineral profiling of moringa leaf extract: A contrastive study of solid-liquid extraction methodologies DOI Creative Commons

T. Arumugam,

Sandeep Gunalan,

Premalakshmi Velu

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(24), P. e40909 - e40909

Published: Dec. 1, 2024

The global food system is plagued by legitimacy and stability issues due to climate ecosystem disruptions, contributing widespread malnutrition. A significant portion of the population experiences undernourishment, overweight, micronutrient deficiencies from unhealthy diets. Addressing these challenges necessitates regular consumption essential nutrients plant sources. Among various crops,

Language: Английский

Citations

1
Recent Advances in the Epidemiology of Pathogenic Agents DOI Creative Commons
Wei‐Chuan Chen, Yusen Eason Lin

Pathogens, Journal Year: 2024, Volume and Issue: 13(3), P. 263 - 263

Published: March 19, 2024

The COVID-19 pandemic has underscored the pivotal role of epidemiology in studying pathogenic agents [...]

Language: Английский

Citations

0
Redefining Vaccines: Nucleic Acid Vaccines Encoding Short Therapeutic Peptides DOI
Zhen Yun Siew, Pooi Pooi Leong, Wong Siew Tung

et al.

Published: Jan. 1, 2024

Language: Английский

Citations

0
Comparative quantum-mechanical characterization of the molecules acacetin and curcumin to understand their antioxidant, anti-inflammatory, anticancer, and neuroprotective functions DOI Creative Commons
Juan Carlos Santiago-Jiménez,

Guadalupe Ortiz-Cabrera,

Gabriel Ramírez-Damaso

et al.

MRS Advances, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

Language: Английский

Citations

0
Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3′-Processing Suppression DOI Creative Commons
Sharif Karim Sayyed, Marzuqa Quraishi,

D. S. Prabakaran

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 18(1), P. 30 - 30

Published: Dec. 29, 2024

Background: The global AIDS pandemic highlights the urgent need for novel antiretroviral therapies (ART). In our previous work, Zinc C295 was identified as a potent HIV-1 integrase strand transfer (ST) inhibitor. This study explores its potential to also inhibit 3′-processing (3′P), thereby establishing dual-targeting capability. Methods: inhibitory activity of against 3′P evaluated using modified in vitro assay adapted from earlier ST inhibition studies. Molecular docking and molecular dynamics simulations were employed analyse C295’s interactions with allosteric site integrase. Results: demonstrated significant assays (IC50 = 4.709 ± 0.97 µM). Computational analyses revealed key within enzyme’s site, providing insights into dual mechanism. Conclusions: establishes it promising candidate next-generation ART. Its dual-action mechanism may offer advantages enhancing treatment efficacy addressing drug resistance. Further studies are warranted evaluate therapeutic clinical settings.

Language: Английский

Citations

0