Computational Evidence for Bisartan Arginine Blockers as Next-Generation Pan-Antiviral Therapeutics Targeting SARS-CoV-2, Influenza, and Respiratory Syncytial Viruses DOI Creative Commons

Harry Ridgway,

Vasso Apostolopoulos,

Graham J. Moore

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(11), P. 1776 - 1776

Published: Nov. 14, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, designed to target multiple viral pathogens simultaneously by focusing on shared molecular features, such as common metal cofactors conserved residues in catalytic domains. This study introduces a new generation of potent sartans, known bisartans, engineered our laboratories with negative charges from carboxylate tetrazolate groups. These anionic tetrazoles interact strongly cationic arginine cations (e.g., Zn2+) within host sites, including the SARS-CoV-2 ACE2 receptor, influenza H1N1 neuraminidases, RSV fusion protein. Using virtual ligand docking dynamics, we investigated how bisartans their analogs bind these receptors, potentially blocking infection through pan-antiviral mechanism. Bisartan, ACC519TT, demonstrated stable high-affinity key domains NSP3, neuraminidase, protein, outperforming FDA-approved like Paxlovid oseltamivir. It also showed strong binding arginine-rich furin cleavage sites S1/S2 S2′, suggesting interference SARS-CoV-2’s spike protein cleavage. results highlight potential tetrazole-based promising candidates developing broad-spectrum antiviral therapies.

Language: Английский

Spatial Analysis of the Cholera Epidemic: Outbreak and Death DOI Open Access
Mitra Mohammadi, Sasan Ghorbani Kalkhajeh, Sedigheh Veisi

et al.

The Open Public Health Journal, Journal Year: 2025, Volume and Issue: 18(1)

Published: March 21, 2025

Background Cholera is a global threat that occurs as result of weak public health. The aim the data re-analysis study was spatial modeling cholera outbreak and mortality. Methods Data on mortality obtained from website World Health Organization. database created using ArcGIS software statistical tests related maps were extracted. Getis-Ord-Gi statistic used for this purpose during years 2000-2021. Results hot spots in 2000 mainly found Africa, 2010-2013 shifted to American continent (Haiti), cold concentrated European countries (Getis-Ord-Gi / Sig = 90%, 95%, 99%). In total, deaths 81241 which constituted be follows: Africa 80.64%, America 12.48%, Asia 6.68% Oceania 0.18%. One death reported Europe. maximum 2010 (7826) minimum 2020 (839). recent years, trend outbreaks has been declining over last 10 years. Conclusion According WHO, continuous reporting required developing correct strategy. This allows health planners managers visually assess, inform, quickly identify cholera-related centers geographical information system (GIS) software.

Language: Английский

Citations

0
Computational Evidence for Bisartan Arginine Blockers as Next-Generation Pan-Antiviral Therapeutics Targeting SARS-CoV-2, Influenza, and Respiratory Syncytial Viruses DOI Creative Commons

Harry Ridgway,

Vasso Apostolopoulos,

Graham J. Moore

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(11), P. 1776 - 1776

Published: Nov. 14, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, designed to target multiple viral pathogens simultaneously by focusing on shared molecular features, such as common metal cofactors conserved residues in catalytic domains. This study introduces a new generation of potent sartans, known bisartans, engineered our laboratories with negative charges from carboxylate tetrazolate groups. These anionic tetrazoles interact strongly cationic arginine cations (e.g., Zn2+) within host sites, including the SARS-CoV-2 ACE2 receptor, influenza H1N1 neuraminidases, RSV fusion protein. Using virtual ligand docking dynamics, we investigated how bisartans their analogs bind these receptors, potentially blocking infection through pan-antiviral mechanism. Bisartan, ACC519TT, demonstrated stable high-affinity key domains NSP3, neuraminidase, protein, outperforming FDA-approved like Paxlovid oseltamivir. It also showed strong binding arginine-rich furin cleavage sites S1/S2 S2′, suggesting interference SARS-CoV-2’s spike protein cleavage. results highlight potential tetrazole-based promising candidates developing broad-spectrum antiviral therapies.

Language: Английский

Citations

0