In Silico Design of miniACE2 Decoys with In Vitro Enhanced Neutralization Activity against SARS-CoV-2, Encompassing Omicron Subvariants DOI Open Access

Jenny Andrea Arévalo-Romero,

Gina López-Cantillo,

Sara Moreno-Jiménez

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10802 - 10802

Published: Oct. 8, 2024

The COVID-19 pandemic has overwhelmed healthcare systems and triggered global economic downturns. While vaccines have reduced the lethality rate of SARS-CoV-2 to 0.9% as October 2024, continuous evolution variants remains a significant public health challenge. Next-generation medical therapies offer hope in addressing this threat, especially for immunocompromised individuals who experience prolonged infections severe illnesses, contributing viral evolution. These cases increase risk new emerging. This study explores miniACE2 decoys novel strategy counteract variants. Using silico design molecular dynamics, blocking proteins (BPs) were developed with stronger binding affinity receptor-binding domain multiple than naturally soluble human ACE2. BPs expressed E. coli tested vitro, showing promising neutralizing effects. Notably, BP9 exhibited an average IC50 4.9 µg/mL across several variants, including Wuhan strain, Mu, Omicron BA.1, BA.2 low demonstrates potent ability BP9, indicating its efficacy at concentrations.Based on these findings, emerged therapeutic candidate combating evolving thereby positioning it potential emergency biopharmaceutical.

Language: Английский

In Silico Design of miniACE2 Decoys with In Vitro Enhanced Neutralization Activity against SARS-CoV-2, Encompassing Omicron Subvariants DOI Open Access

Jenny Andrea Arévalo-Romero,

Gina López-Cantillo,

Sara Moreno-Jiménez

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10802 - 10802

Published: Oct. 8, 2024

The COVID-19 pandemic has overwhelmed healthcare systems and triggered global economic downturns. While vaccines have reduced the lethality rate of SARS-CoV-2 to 0.9% as October 2024, continuous evolution variants remains a significant public health challenge. Next-generation medical therapies offer hope in addressing this threat, especially for immunocompromised individuals who experience prolonged infections severe illnesses, contributing viral evolution. These cases increase risk new emerging. This study explores miniACE2 decoys novel strategy counteract variants. Using silico design molecular dynamics, blocking proteins (BPs) were developed with stronger binding affinity receptor-binding domain multiple than naturally soluble human ACE2. BPs expressed E. coli tested vitro, showing promising neutralizing effects. Notably, BP9 exhibited an average IC50 4.9 µg/mL across several variants, including Wuhan strain, Mu, Omicron BA.1, BA.2 low demonstrates potent ability BP9, indicating its efficacy at concentrations.Based on these findings, emerged therapeutic candidate combating evolving thereby positioning it potential emergency biopharmaceutical.

Language: Английский

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