The recent COVID-19 pandemic has demonstrated the vulnerabilities of our society to infectious diseases and the limitations of the tools available for viruses detection. Polymerase chain reaction (PCR) and antigens tests have been useful to monitor and contain the extension of the last pandemic, however it demonstrated to have severe limitations. PCR is a highly reliable technique, but it can be slow and requires specialized equipment, therefore is not suitable for mass screening. Antigen tests are faster, cheaper, and more portable, but not totally trustable and unable to detect low concentrations of the virus. To better prepare for future pandemics and effectively detect unknown viruses, there is a need for new platforms that can rapidly and selectively identify pathogens with high reliability.
Viruses are tiny infectious agents that rely on host cells, such as human cells, to multiply and spread. In order to infect a host cell, viruses must first locate and attach to specific molecules on the surface of the cell. These molecules, called receptors, act as a kind of lock that the virus must “key” into in order to enter the cell.
Viruses have evolved to be highly adept at finding and binding to receptors, and they often do so with great precision. As a result, receptors can be used as a kind of “bait” for detecting and identifying viruses. By using human receptors as bait, it is possible to attract and capture viruses that are actively seeking out host cells to infect. In this way, receptor-based techniques can be a powerful tool for detecting and studying viruses in the laboratory.
One potential strategy is to utilize human membrane proteins, such as Angiotensin-converting enzyme 2 (ACE2), in the detection process. ACE2 is an enzyme expressed on the membranes of cells which can interact with the spike protein of coronaviruses, serving as an entry point for the virus to enter host cells.
Using ACE2 as a receptor has several advantages over traditional approaches that rely on monoclonal antibodies (mAbs). First, the expression of a monoclonal antibody with high selectivity for a specific virus requires the isolation of the virus. With ACE2, it is possible to detect infective viruses without the need for virus isolation, as the protein can selectively recognize viruses that enter cells through this human receptor. Additionally, using ACE2 as a receptor may make the biosensor more resistant to virus mutations, which can reduce the efficacy of mAb-based biosensors. For example, SARS-CoV-2, the virus that causes COVID-19, has undergone several mutations in just a few years, and mAb-based biosensors may lose their effectiveness when the virus mutates and changes the composition of its surface.
In a recent study 1, the researchers combined the ability of ACE2 to interact with coronavirus spike proteins with the sensitivity of graphene field effect transistors (gFETs) to create a platform for detecting pathogenic viruses. gFETs are highly sensitive sensors that can be used to detect a range of biologically relevant molecules, including viruses. The platform has the potential to detect SARS-CoV-2, the virus that causes COVID-19, at single virus concentration.
Overall, this work demonstrates the potential of using ACE2 and gFETs for detecting a wide range of viruses. By using human membrane proteins as receptors and combining them with sensitive detection technologies like gFETs, it may be possible to create platforms that can rapidly and accurately detect viruses, even those that have not yet been isolated and identified. This could be a valuable tool for preventing future pandemics and controlling infectious diseases. Recently, the FLUFet project, which originated from the concepts presented in this work, received an EIC Pathfinder grant from the EU.
Alessandro Silvestri,a Ivan Coluzzab,c Alejandro Criadod,a
aCenter for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 194, 20014 Donostia-San Sebastián, Spain.
bIkerbasque, Basque Foundation for Science, 48013 Bilbao, Spain
cBCMaterials, Basque Center for Materials, Applications and Nanostructures, Bld. Martina Casiano, UPV/EHU Science Park, Barrio Sarriena s/n, 48940 Leioa, Spain. Email: firstname.lastname@example.org
dUniversidade da Coruña, CICA – Centro Interdisciplinar de Química e Bioloxía, Rúa as Carballeiras, 15071 A Coruña, Spain. E-mail: email@example.com
- Alessandro Silvestri, Julian Zayas-Arrabal, Mariano Vera-Hidalgo, Desire Di Silvio, Cecilia Wetzl, Marta Martinez-Moro, Amaia Zurutuza, Elias Torres, Alba Centeno, Arantxa Maestre, Juan Manuel Gómez, María Arrastua, Marta Elicegui, Nerea Ontoso, Maurizio Prato, Ivan Coluzza and Alejandro Criado (2023) Ultrasensitive detection of SARS-CoV-2 spike protein by graphene field-effect transistors Nanoscale doi: 10.1039/D2NR05103F ↩