Transduced MSCs that express engineered ACE2 could be highly beneficial to combat COVID-19. Engineered ACE2 can act as decoy targets for the virus, preventing its entry into healthy lung cells. To this end, genetic engineering techniques were used to integrate the ACE2 gene into the MSCs genome. The MSCs were evaluated for proper expression and functionality. The mutated form of ACE2 was characterized using various techniques such as protein expression analysis, binding affinity against spike protein, thermal stability assessment, and enzymatic activity assays. The functionality of the mACE2 was assessed on SARS-CoV-2 using the virus-neutralizing test. The obtained results indicated that by introducing specific mutations in the ACE2 gene, the resulting mutant ACE2 had enhanced interaction with viral spike protein, its thermal stability was increased, and its enzymatic function was inhibited as a decoy receptor. Moreover, the mACE2 protein showed higher efficacy in the neutralization of the SARS-CoV-2. In conclusion, this study proposes a novel approach with potential benefits such as targeted drug delivery and reduced side effects on healthy tissues. These transduced MSCs can also be used in combination with other anti-COVID-19 treatments. Design of similar engineered biomolecules with desired properties could also be used to target other diseases.
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http://dx.doi.org/10.1016/j.ijbiomac.2024.134066 | DOI Listing |
Adv Sci (Weinh)
January 2025
Department of Orthopedic Surgery, Changzheng Hospital, Naval Medical University, Shanghai, 200003, P. R. China.
Nucleus pulposus cell (NPC) senescence contributes to intervertebral disc degeneration (IVDD). However, the underlying molecular mechanisms are not fully understood. In this study, it is demonstrated that angiotensin-converting enzyme 2 (ACE2) counteracted the aging of NPCs and IVDD at the cellular and physiological levels.
View Article and Find Full Text PDFGlycobiology
January 2025
Department of Biochemistry, Dorothy Crowfoot Hodgkin Building, University of Oxford, South Parks Road, OX1 3QU, United Kingdom.
Abdala is a COVID-19 vaccine produced in Pichia pastoris and is based on the receptor-binding domain (RBD) of the SARS-CoV-2 spike. Abdala is currently approved for use in multiple countries with clinical trials confirming its safety and efficacy in preventing severe illness and death. Although P.
View Article and Find Full Text PDFNutrients
December 2024
Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China.
Food protein-derived antihypertensive peptides have attracted substantial attention as a safer alternative for drugs. The regulation of the renin-angiotensin system (RAS) is an essential aspect underlying the mechanisms of antihypertensive peptides. Most of the identified antihypertensive peptides exhibit the angiotensin-converting enzyme (ACE) inhibitory effect.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that emerged in late 2019 and rapidly spread worldwide, causing the COVID-19 pandemic. The spike glycoprotein (S protein) plays a crucial role in viral target recognition and entry by interacting with angiotensin, converting enzyme 2 (ACE2), the functional receptor for the virus, via its receptor binding domain (RBD). The RBD availability for this interaction can be influenced by external factors, such as fatty acids.
View Article and Find Full Text PDFSci Adv
January 2025
Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Measuring virus in biofluids is complicated by confounding biomolecules coisolated with viral nucleic acids. To address this, we developed an affinity-based microfluidic device for specific capture of intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach used an engineered angiotensin-converting enzyme 2 to capture intact virus from plasma and other complex biofluids.
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