The Achille's heel of SARS-CoV-2 identified and hit
Right now, one of the biggest challenges for the global scientific community is combatting SARS-CoV-2 and the other fearsome coronaviruses. The objective is to find a treatment that will block the virus from entering cells.
The idea that the proliferation of SARS-CoV-2 can be prevented by inhibiting a specific molecular target responsible for the progression of the virus that has just entered the cell was born in the laboratory of the Unit of Histology and Medical Embryology of Antonio Filippini of the Department of Anatomical, Histological, Medical-Legal Sciences and Locomotor Apparatus of Sapienza University of Rome, thanks to strong expertise on signalling systems and endocytic intracellular traffic.
From hypothesis to experimentation. The Achille's heel of coronaviruses has been identified in the lysosomal TPC (Two-PoreChannels) ion channels, which have been studied for years by the Sapienza research group which, in collaboration with Armando Carpaneto of the University of Genoa, has recently discovered Naringenin, a natural substance made from citrus fruits and other food plants, as an effective weapon to inhibit these channels. The paper has been published on the journal Pharmacological Research.
To test the hypothesis, it was necessary to create bridges between cell biology and virology expertise, involving virologists from the universities of Rome and Milan. In particular, the group of researchers at the Sapienza Laboratory of Virology led by Guido Antonelli, discovered that the treatment of cells with Naringenin prevents the infection of more than one type of coronavirus, thus blocking the progress of the infection. In addition to these results, the team of the Microbiology Laboratory of the University Vita-Salute San Raffaele, led by Massimo Clementi, has shown that, at the same doses, SARS-CoV-2 infection is also stopped.
A further advantage for a possible therapeutic application of Naringenin is that this molecule can effectively counteract the harmful production of inflammation cytokines, the so-called inflammatory storm, which is triggered during viral infection.
"The identification of a cellular target, demonstrating that it is possible to hit it effectively, represents a substantial step forward towards the ambitious goal of stopping the Covid-19 epidemic – says Antonio Filippini. We are already working on the next challenge, with the important help of new nanotechnological expertise within Sapienza. The aim is to identify the optimal formulation to deliver the drug at the lowest possible concentrations to the upper airways, the critical front line for fighting the infection, effectively and selectively."
Naringenin is a powerful inhibitor of SARS-CoV-2 infection in vitro – Nicola Clementi, Carolina Scagnolari, Antonella D’Amore, Fioretta Palombi, Elena Criscuolo, Federica Frasca, Alessandra Pierangeli, Nicasio Mancini, Guido Antonelli, Massimo Clementi, Armando Carpaneto, Antonio Filippini – Pharmacological Research, 2020. DOI https://doi.org/10.1016/j.phrs.2020.105255
Department of Anatomical, Histological, Medical-Legal Sciences and Locomotor Apparatus