Starting from December 2019 in China, a novel virus of the Coronaviridae family, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading worldwide. SARS-CoV-2 infections range from asymptomatic to mild symptoms, up to severe acute respiratory distress syndrome (ARDS) and death. The development of new 3D models that mimic healthy and pathological lung tissue to understand the novel SARS-CoV-2 mechanisms of infection better and spreading of the virus is of paramount importance. Similarly, the identification of natural compounds able to act as antiviral drugs that can inhibit SARS-CoV-2 infection and/or replication and the development of new platform for controlled and localize delivery of therapeutic drugs would represent a powerful step to enhance the response to a possible second wave of the pandemic virus. In this project, we will try to generate a 3D model of healthy and pathological lung tissue and utilize it for experimental in vitro CoV infection models, with the low-pathogenic CoV OC43, 229E, and NL63, to understand better virus mechanism of action and spreading in a physiological environment. We will evaluate the use of candidate natural compounds such as glycyrrhizin for its ability to inhibit viral growth or decrease viral replication, in both 2D and 3D cell culture of infected A549 permissive cell line. We will then evaluate the use of functionalized silica and zinc nanowires for their ability to be used as a platform for controlled and localized drug delivery and assess the efficacy, function, and entry efficiency of the released drug in the 3D infected lung tissue model.
This project has a strong interdisciplinary approach bringing together experts tissue engineers, molecular biologists, virologists, and electrical engineers leader in nanowire technologies for health applications aiming to start to answer different issues in the new SARS-COv-2 pandemic. The project aims to begin understanding how the difference in tissue microenvironment could influence virus infection, replication, and spreading. The use of these tissue models could also be a better and powerful tool in testing candidate drugs as it better recapitulates the in vivo environment's complexity, both in a healthy and pathological condition, as compared to classical 2D culture. methods
This would allow the use of 3D models also to better understand the broad range in patient response and could be of paramount importance, both for the therapeutic and prognostic value, as the altered microenvironment could strongly play a role not only in virus pathogenicity and immune cell inflammatory response but also in the drug bioavailability in the infected site. We will also evaluate a silicon and zinc functionalized platform for controlled and localized delivery. This approach has been shown to be advantageous in many other drug delivery approaches and could potentially be suitable for the release of a broad array of drugs, therefore, having a significant impact not only for the cure of SARS-COv-2 patients but also potentially other diseases. Moreover, it has already been tested in vivo for the release of nucleic acid showing excellent biosafety and thus the potential for an easy and fast in vivo application. Lastly, we will also try to evaluate naturally-derived drugs such as Glycerizina, as it has been already shown to have antiviral effects on other viruses of the Coronaviridae family, with the potential to be easily translated in vivo as well as reduce potential side effects that have been currently observed with other candidate drug.