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We have learned more about the SARS-CoV-2 virus using its proteins as keys

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During the ongoing COVID-19 pandemic, understanding the virus’ proteins has been at the core of SARS-CoV-2 research, because the virus invades human cells through protein contacts. Several universities in Sweden have facilities that produce proteins for various research projects that are part of Protein Production Network Sweden–University of Gothenburg through the Mammalian Protein Expression (MPE) Core Facility.

Through its national collaboration, the Protein Production Network Sweden (PPNS) has contributed unique expertise and equipment to produce the various proteins of the coronavirus, which has been fundamental for research on the virus.

Inhibitors for treatment

“Because PPNS specializes in protein production, we have been able to develop and map the structure of different proteins from the SARS-CoV-2 virus. In several locations, we have produced the important SARS-CoV-2 protease Mpro, which is needed to find inhibitors that can act as possible medications,” says Uwe Sauer, an associate professor and coordinator of the Protein Expertise Platform (PEP), Umeå University.

In an October 2020 study, researchers at Lund University have been able to study inhibitors using viral proteins produced by the Lund Protein Production Platform (LP3). The study mapped the specific protein nsp10, which may help us understand how the virus replicates. It is also useful for finding inhibitors that can affect the protein and thus the virus.

Understanding the coronavirus spikes

The well-known spikes of the coronavirus, which sit like knobs on the virus particle, also consist of proteins that have been produced in several laboratories, including the MPE Core Facility at Sahlgrenska Academy, University of Gothenburg. This has enabled researchers at Sahlgrenska Academy to identify antibodies to the virus – including those in patients who have tested negative for infection by other methods.

The virus attaches to human cells through the spike proteins, transmitting the infection. As a result, antibodies are important in preventing the virus from spreading between cells.

“In all protein platforms in Sweden, we strive to use our expertise and equipment to respond quickly to the challenges posed by the ongoing pandemic, but we also see that the knowledge we gain can be used in the future for still unknown viruses,” says Malin Bäckström, unit manager at MPE in Gothenburg.

Unique Swedish collaboration

The protein facilities in Sweden collaborate through PPNS, their national network. The Swedish collaboration is unique in Europe, says Wolfgang Knecht, an associate professor at Lund University and manager at LP3:

“As far as we know, no similar university collaboration exists at the national level in other countries in Europe. Since 2013, when the PPNS network was founded, the platforms together have been able to provide high-quality research support to a large number of researchers in various fields, and we now have a special focus on projects related to SARS-CoV-2.”

FAKTA

Five fields in COVID-19 research where protein production has been a key factor in increasing knowledge about the virus:

Serology, which measures the presence of antibodies in patients. Conducted at the University of Gothenburg and Stockholm University/SciLifeLab. a

Testing of antibodies developed to combat SARS-CoV-2 for therapy or diagnostics, using proteins produced within PPNS. Conducted at Stockholm University/SciLifeLab.

Production of the most important SARS-CoV-2 virus protease (Mpro) to find inhibitors that can act as medication candidates and to determine its structure. Conducted at Karolinska Institutet and Umeå University.

Production of various polymerases for use in polymerase chain reaction diagnostics for the SARS-CoV-2 virus. Conducted at Karolinska Institutet and Umeå University. b

Determining the structure of different proteins from SARS-CoV-2. Conducted at Lund University and Karolinska Institutet. c

Related Scientific Articles:

a. Marklund et al. Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-respondersPLoS One 2020 Oct 21;15(10):e0241104.

b. Alekseenko et al. Detection of SARS-CoV-2 using non-commercial RT-LAMP regents and raw samples. https://www.medrxiv.org/content/10.1101/2020.08.22.20179507v1

c. Rogstam et al. Crystal Structure of Non-Structural Protein 10 from Severe Acute Respiratory Syndrome Coronavirus-2 Int J Mol Sci 2020 Oct 6;21(19):7375.