New research has succeeded in identifying different molecular compounds that prevent the entry of the SARS-CoV-2 virus into cells, inhibiting the interaction that occurs between the spike protein of the virus and cell receptors. These molecules act in very early stages of the viral replicative cycle, so they could prevent the hyperactivation of the immune system that triggers the cytokine storm during the worsening of COVID-19. These compounds could be used to develop antiviral drugs against SARS-CoV-2.
This project has been developed in Spain by researchers from the Higher Council for Scientific Research (CSIC).
The compounds identified as virus entry inhibitors are molecules belonging to the research group led by María Jesús Pérez Pérez, a CSIC researcher at the Institute of Medical Chemistry (IQM-CSIC). “Using the simile of the door, they try to block the main door through which the virus accesses the cell interior. In this way, they would protect the cells from viral infection ”, explains Pérez, who leads the project together with Sonsoles Martín Santamaría, from the Margarita Salas Biological Research Center (CIB-CSIC), Ron Geller, from the Institute of Integrative Biology and Sistemas, mixed center of the CSIC and the University of Valencia (I2SysBio-CSIC-UV) and Alberto Marina and Vicente Rubio, of the Institute of Biomedicine of Valencia (IBV-CSIC).
The researchers tested the drugs using viral pseudoparticles with the SARS-CoV-2 virus spike protein expressed on their surface. Next, their ability to interfere between the binding of the spike protein with the cell receptor and subsequent infection was analyzed.
Colorized photograph taken by means of an electron microscope showing a human cell (in red) infected with the SARS-CoV-2 coronavirus (the yellow particles). (Image: US National Institute of Allergy and Infectious Diseases, NIH)
“We have achieved the inhibition of the entry of the virus at low concentrations without generating toxicity in the cells. This generates a broad selectivity index, a parameter that measures the difference in concentrations between antiviral activity and toxicity against uninfected cells. It is an important factor when developing antiviral drugs ”, says the CSIC researcher.
The identified compounds act in very early stages of the viral replicative cycle. By preventing the virus from replicating in the cell, they could avoid the effects of the cytokine storm. “Its use as a preventive treatment for infection could even be valued. From now on, a long journey begins that includes its preclinical study and its efficacy evaluation in an animal model ”, concludes Pérez.
The project is funded by the CSIC Global Health Platform and the Overcome COVID-19 Fund (Crue-CSIC-Santander). (Source: CSIC)