Development of a mutant aerosolized ACE2 that neutralizes SARS-CoV-2 in vivo

mBio, Journal Year: 2024, Volume and Issue: 15(6)

Published: May 21, 2024

The rapid evolution of SARS-CoV-2 variants highlights the need for new therapies to prevent disease spread. SARS-CoV-2, like SARS-CoV-1, uses human cell surface protein angiotensin-converting enzyme 2 (ACE2) as its native receptor. Here, we design and characterize a mutant ACE2 that enables affinity purification dimeric by altering active site autoproteolytic digestion C-terminal His

Language: Английский

Effect of Maraviroc and/or Favipiravir plus systemic steroids versus systemic steroids only on the viral load of adults with severe COVID-19: clinical trial

F1000Research, Journal Year: 2024, Volume and Issue: 13, P. 180 - 180

Published: June 11, 2024

Background Coronavirus disease 2019 (COVID-19) has created the need to evaluate drugs such as favipiravir (FPV), an antiviral inhibitor of RNA-dependent RNA-polymerase (RdRp), and Maraviroc (MVC), antiretroviral that antagonizes chemokine receptor CCR5, which could affect modulation inflammation viral replication in treatment COVID-19. We sought effect MVC and/or FPV plus systemic steroid (SS) vs. SS alone on load progression critical disease. Methods Sixteen patients with severe COVID-19 were evaluated three arms: 1) only (n=6), 2) one test drug or (n=5), 3) both (MVC FPV, n=5). The was determined for N, E, RdRp genes. Results A significant decrease observed groups, a larger size group combined drugs. genes Cohen’s d 120%, 123%, 50%, respectively. Conclusions largest reduction, measured by size, combination group; however, no statistical significance found, it did not prevent illness.

Language: Английский

Disulfide Bond Engineering of Soluble ACE2 for Thermal Stability Enhancement

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9919 - 9919

Published: Sept. 14, 2024

Although the primary pandemic of SARS-CoV-2 is over, there are concerns about resurgence next wave related viruses, including a wide range variant viruses. The soluble ACE2 (sACE2) inhibits spike protein interaction and has potential as variant-independent therapeutic against SARS-CoV-2. Here, we introduce novel disulfide bonds in wild-type sACE2-Fc by structure-guided mutagenesis, aiming to improve its stability. stability each mutant was assessed thermal shift assay screen mutants with increased As result, identified significantly melting temperature. X-ray crystal structure determination sACE2 confirmed correct formation designed bond, were no significant structural disturbances. We also proved that thermostable preserved binding affinity comparable both molecular cellular environments, suggesting potential.

Language: Английский