Scientists identify possible targets for the coronavirus vaccine and therapy

Researchers show that in laboratory studies, antibodies that can neutralize the virus that causes SARS will reduce how well the current coronavirus infects cells. They also use an approved drug to reduce virus entry into cells.

Scientists are nudging closer to forming a new coronavirus vaccine.
Scientists are nudging closer to forming a new coronavirus vaccine.

With global COVID-19 cases outperforming 100,000, researchers are finding ways to prevent new viral infections.

The new coronavirus, named SARS-CoV-2, has strong similarities with other coronavirus viruses in the family, particularly those that cause SARS and MERS.

Two new papers recently appeared in the Cell journal, exploring how cells are infected by SARS-CoV-2.

So, how exactly is the virus gaining cell entry and why is it important to know that?

Understanding the target molecules that promote viral entry into cells is of paramount importance to understanding how to avoid this cycle.

Both papers claim that SARS-CoV-2 utilizes the same viral entry mechanism used by the SARS virus (SARS-CoV).

More specifically, both research teams used an enzyme inhibitor and antibodies against the SARS virus to investigate ways of stopping this cycle.

Coronavirus infection route

SARS-CoV-2 the new coronavirus is a type of virus called an enveloped RNA virus.

This means that their genetic material is encoded in single-stranded RNA molecules surrounded by a cell membrane taken from the cell it was last infected with.

When a cell is infected with enveloped viruses they do this using a two-stage cycle.

The first step consists of connecting to a receptor on the target cell surface. The second is fusion with a cell membrane, either on the cell surface or at an inside spot.

In the case of coronaviruses the first step involves a biochemical alteration of specific proteins in the viral envelope, called spike (S) proteins. This phase is called the priming of proteins S.

The S-protein priming enzymes are potential therapeutic targets as inhibiting their activity will prevent a virus from entering a cell.

“Unraveling the cellular factors SARS-CoV-2 uses for entry could provide insights into viral transmission and reveal therapeutic targets,” one of the new papers in Cell writes the authors.

The senior author of the study is Stefan Pöhlmann, a professor of infection biology at Georg-August-University and head of the German Primate Center’s Infection Biology Unit, both based in Göttingen, Germany.

Pöhlmann and his colleagues show evidence that the protein SARS-CoV-2 S binds to the same receptor as the protein SARS virus. The receptor is called the enzyme 2 or ACE2 which converts angiotensin.

However, an earlier paper in the journal Nature already included ACE2 as the receptor allowing SARS-CoV-2 to infect cells.

Apart from providing more proof of the function of ACE2, Pöhlmann and the team also saw that the new coronavirus S protein, like SARS-CoV, uses an enzyme called TMPRSS2 for S protein priming.

Importantly, they demonstrated that “camostat mesylate, a TMPRSS2 inhibitor, prevents lung cell infection with SARS-CoV-2.”

Camostat mesylate is a drug approved for pancreatitis treatment in Japan. In the paper the writers explain:

“This compound or related ones with potentially increased antiviral activity could thus be considered for off-label treatment of SARS-CoV-2-infected patients.”

Towards a SARS-CoV-2 vaccine

Pöhlmann and his colleagues also investigated whether antibodies made by people who had a prior SARS diagnosis would prevent the entry of SARS-CoV-2 virus into cells.

They found that antibodies to the protein SARS-CoV S reduced how well a laboratory model virus with the protein SARS-CoV-2 S could infect cells. They also saw similar results against S-proteins developed in rabbits with antibodies.

“While confirmation with an infectious virus is pending, our results indicate that neutralizing antibody responses produced against SARS-S could provide some defense against SARS-CoV-2 infection, which could have implications for outbreak control,” the team writes in the paper.

But it is not only Pöhlmann and his colleagues who are studying the potential to use antibodies to SARS as a SARS-CoV-2 vaccine.

David Veesler, an assistant professor of biochemistry at Washington University in Seattle, provides further proof that the virus reaches target cells through ACE2 in a Cell-published paper.

In addition to his colleagues, he also studied antibodies to identify potential vaccines against SARS S protein fragments.

The team showed that antibody serum from four separate mice could reduce SARS-CoV-2 S infection by 90 percent with a laboratory model virus.

But more testing is needed before there’s a much-needed SARS-CoV-2 vaccine available.

Clinical trials to show safety and effectiveness would form the basis for turning these candidates for the vaccine into safe products for use.

Last month in Europe, the European Medicines Agency declared it was taking “concrete actions to speed up the development and availability of pharmaceutical products for the treatment and prevention of the new coronavirus.”

Meanwhile, the Department of Health and Human Services is partnering with Janssen Research and Development, part of the Johnson & Johnson pharmaceutical company, to create a vaccine against SARS-CoV-2 in the United States. Also underway is a clinical trial, funded by the National Institute for Allergy and Infectious Diseases using a novel form of RNA-based vaccine.

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