Visualizing and decoding to fight SARS-CoV-2 more effectively

Virologists, particularly those from the Bordeaux campus, have been strongly involved in the fight against Covid-19. Interview with Vincent Parissi, CNRS researcher in molecular virology at the Fundamental Microbiology and Pathogenicity Laboratory*.

  • 10/05/2021

Microscopie © Vincent Parissi - MFP Microscopie © Vincent Parissi - MFP

What are your research topics?

In the MoBileVIR team** that I lead, we are trying to understand the mobility mechanisms of pathogenic genomes. In other words, how a pathogen (virus, bacterium) allows its genome (its genetic information) to be transferred from one individual to another, from one cell to another or within the same cell. Understanding these mechanisms allows us to know at what point in the process we could block viral replication, and therefore develop remedial strategies.

We mainly focus our research on retroviruses, such as HIV-1, RNA viruses that have the double capacity to infect a cell, but also to integrate their genome in a lasting way and to become unassailable. It is also important to study these because some retroviruses are infectious agents of humans, with significant health risks - as is the case with HIV-1, the virus responsible for AIDS.

How did you come to work on SARS-CoV-2?

For years, we have been developing tools to decipher the integration process of retroviruses. We are able to visualize, measure and quantify the physical interactions that take place between the virus and the cell. Often, these approaches can be transposed to other viruses... including the coronavirus!

When the health crisis broke out, we were under lockdown, which was very frustrating as we had tools that could be transposed to SARS-CoV-2... It was therefore urgent to go back to the laboratory! Fortunately, we were able to return quickly, and since April 2020, we have adapted and made these tools available to the community. These tools currently make it possible to study a very early phase of the infection: that of the viral attachment to the host cell with the interaction between the viral spike protein and its host ACE2 receptor.

Can all laboratories study SARS-CoV-2?

To study this highly pathogenic virus in its natural infectious cycle, it must be handled in a class P3 containment laboratory. This unit's work was conducted by Marie-Line Andréola. However, P3 laboratories are in high demand and are not always easy to access for the whole scientific community. This is where our desire to provide tools to study the virus in a cellular context emerged, but in a simplified and less dangerous way, with fewer constraints.

We have thus developed a cellular model using viruses derived from the natural virus that are infectious but not replicative: they can enter the cell but cannot replicate and produce viruses. Developed in collaboration with the Vect'UB vectorology platform at the University of Bordeaux, these "hybrid" models are now available and can be used by any laboratory.

Do you also carry out work on remedial aspects?

Yes, even though our team is more focused on basic studies, we have started to look for remedial strategies targeting SARS-CoV-2. Last summer, after activating our collaboration network, we received over a thousand molecules to test physically with our tools. It was a very intense period! We also pre-screened over 70,000 compounds with a computer modeling tool, and selected about 20 for physical testing as well.

Among all these molecules, three good candidates were validated in the simplified cell system. After testing in the P3 laboratory on natural viral models, two compounds were found to be effective against the original SARS-CoV-2 strain. These molecules, which are in the process of being patented and published, will subsequently be tested on animal models.

As a virologist, what was your experience of the last few months?

Initially, I felt angry. Many teams have been working on coronaviruses for many years without being supported before the pandemic. If research projects on these viruses had been funded since the first SARS emergence in the early 2000s, we might not be where we are today... There followed a phase of frustration at having tools that could be used but were inaccessible because we were in lockdown, and then a phase of very intense work began. One year later, the pace is still as high as ever. What is very positive for the long term is that some collaborations born from the work on coronavirus are now extending to projects on retroviruses!

I was impressed by the enormous sharing of knowledge and materials, the transparency and willingness to work together within the international scientific community... This is something I have never felt before, the research around HIV-1 is much more competitive. Between AIDS and Covid-19, I have now experienced two pandemics as a virologist working on these themes... but living through the very beginning of a new pandemic is very unique when you are in this profession.

*Fundamental microbiology and pathogenicity  (MFP - CNRS and University of Bordeaux)

**MobileVIR team - Chromatin dynamics and mobility of pathogenic genomes

Contact

Vincent Parissi
CNRS Research Director at the MFP laboratory