Antiviral Actions of Polyphosphates against SARS-CoV-2 Variants Visualized with Super-resolution Microscopy

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Antiviral Actions of Polyphosphates against SARS-CoV-2 Visualized with Super-resolution Microscopy

byZEISS Microscopy 21 March 2022 2 min read

Introduction

Researching preventative treatments for COVID-19

The global spread of COVID-19 presents a current challenge to medical researchers to develop therapeutic strategies. Dr. Massimo Zollo, a Principle Investigator at CEINGE, Italy, and the Scientific Coordinator of the Task-Force COVID-19 CEINGE, with his collaborator, Dr. Veronica Ferrucci, have published data showing the potential activities of phosphates against SARS-CoV-2 infection. Part of their investigations use the ZEISS Elyra 7 super-resolution microscope system.

Dr. Massimo Zollo (left) with his collaborator, Dr. Veronica Ferrucci, at their ZEISS Elyra 7 super-resolution system.

SARS-CoV-2 Research at CEINGE

The research team at CEINGE focuses on human molecular genetics discoveries.

With the emergence of SARS-CoV-2, the laboratory is carrying out studies to identify:

New rapid patterns of virus detection
Genetic studies to identify the role of disease-related genes in asymptomatic cases
Functional studies to identify the mechanisms of new anti-viral drugs that inhibit the entry and replication of the SARS-CoV-2 virus in primary human cells

Ferrucci, V. *et al*. Long-chain polyphosphates impair SARS-CoV-2 infection and replication. *Science Signaling*. Vol .14, Issue 690. Link

Research Article

In their article in Science Signaling, they describe for the first time the role of polyphosphates (P120) to enhance protein degradation of two crucial component of the Sars-CoV-2 infection: ACE2 and RpRd proteins. Both are key proteins which influence the early and middle phases infection.

Within the manuscript they prove that these effects ameliorate the cytokine storm and negatively influence virus replication within infected cells in vitro, in part with colocalization studies using the ZEISS Elyra 7 super-resolution system.

Super-resolution microscopy using ZEISS Elyra 7 turned out to be a powerful tool to visualize SARS-CoV-2 viral proteins (through immunofluorescence) and/or RNA (via HuluFISH) in specific cellular compartments, such as membrane or cytosol.

Dr. Veronica Ferrucci University Federico II and CEINGE Biotecnologie Avanzate, Italy

HEK 293-ACE2 cells (human embryonic kidney cells genetically modified to express ACE2, the receptor used by SARS-CoV-2 to enter host cells) infected with the virus.

Effects of Polyphosphates Visualized with Super-resolution Microscopy

HEK 293-ACE2 cells (human embryonic kidney cells genetically modified to express ACE2, the receptor used by SARS-CoV-2 to enter host cells) infected with the virus.

HuluFISH analysis with a pan–SARS-CoV-2 probe against the S gene is shown in orange. Antibody staining against ACE2 is shown in red and viral spike protein is shown in green. Cells on the left show the formation of syncytia, viral induced, large multi-nucleated cells which promote viral spread. The cells on the right have been treated with polyphosphates and do not show syncytia formation.

We have three efforts going. Confirm our results in animals. Find additional targets important to the mechanism of action. Produce cGMP PolyP120 particles for Phase 1 and 2 trials with human patients.

Dr. Massimo Zollo University Federico II and CEINGE Biotecnologie Avanzate, Italy