Promising candidates identified for COVID drugs

A team of researchers has identified several candidates for drugs against the coronavirus SARS-CoV-2 at DESY´s high-brilliance X-ray lightsource PETRA III. They bind to an important protein of the virus and could thus be the basis for a drug against Covid-19.

In a so-called X-ray screening, the researchers, under the leadership of DESY, tested almost 6000 known active substances that already exist for the treatment of other diseases in a short amount of time. After measuring about 7000 samples, the team was able to identify a total of 37 substances that bind to the main protease (Mpro) of the SARS-CoV-2 virus, as the scientists report online today in the journal Science. Seven of these substances inhibit the activity of the protein and thus slow down the multiplication of the virus. Two of them do this so promisingly that they are currently under further investigation in preclinical studies. This drug screening – probably the largest of its kind – also revealed a new binding site on the main protease of the virus to which drugs can couple.

Read more on the DESY website

Image: In the control hutch of the PETRA III beamline P11, DESY researcher Wiebke Ewert shows on a so-called electron density map where a drug candidate (green) binds to the main protease of the corona virus (blue).

Credit: DESY, Christian Schmid

New targets for antibodies in the fight against SARS-CoV-2

An international team of researchers examined the antibodies from a large cohort of COVID-19 patients. Due to the way antibodies are made, each person that is infected has the potential to produce many antibodies that target the virus in a slightly different way. Furthermore, different people produce a different set of antibodies, so that if we were to analyse the antibodies from many different patients, we would potentially be able to find many different ways to neutralise the virus.

The research article in the journal Cell is one of the most comprehensive studies of its kind so far. It is available online now and will be published in print on 15 April. These new results now show that there are many different opportunities to attack the virus using different antibodies over a much larger area than initially thought/mapped.

Professor Sir Dave Stuart, Life Sciences Director at Diamond and Joint head of Structural Biology at the University of Oxford, said:

SARS CoV-2 is the virus that causes COVID-19. Once infected with this virus, the human immune system begins to fight the virus by producing antibodies. The main target for these antibodies is the spike protein that protrudes from the virus’ spherical surface. The spike is the portion of the virus that interacts with receptors on human cells. This means that if it becomes obstructed by antibodies, then it is less likely that the virus can interact with human cells and cause infection.

By using Diamond Light Source, applying X-ray crystallography and cryo-EM, we were able to visualise and understand antibodies interact with and neutralize the virus. The study narrowed down the 377 antibodies that recognize the spike to focus mainly on 80 of them that bound to the receptor binding domain of the virus, which is where the virus spike docks with human cells.

Read more on the Diamond website

Image: Figure from the publication showing how the receptor binding domain resembles a human torso.

Credit: The authors (Cell DOI: 10.1016/j.cell.2021.02.032)

World Science Day spotlight: Collaborating to tackle SARS-CoV-2

Science facilities worldwide have been working around the clock to drive forward SARS-CoV-2 research to alleviate the suffering that the COVID-19 pandemic is currently causing.

Today (November 10), in recognition of World Science Day for Peace and Development, the collective efforts of thousands of scientists and technical experts is being marked through this year’s focus – “Science for and with Society in dealing with the global pandemic.”

At the start of the pandemic, the facilities that make up the Lightsources.org collaboration were swift to ensure that rapid access was available for researchers working on SARS-CoV-2. This has led to a large body of research being undertaken at synchrotrons and free electron lasers.  The aims have been varied and include mapping the structure of the virus; finding binding sites for drugs to lock into; screening existing drugs to establish if they have a role to play in treating patients; understanding the impact of the virus on the lungs; and understanding the immune response so vaccines can be designed to illicit an immune response in the body.

A dedicated, regularly updated, web page – Lightsource research for SARS-CoV-2 – draws together all this research, along with other publications and resources.  It also includes links for researchers wishing to gain rapid access for their SARS-CoV-2 experiments.

The World Science Day for Peace and Development was created as a follow-up to the World Conference on Science, organised jointly by UNESCO and the International Council for Science in Budapest (Hungary) in 1999.

By linking science more closely with society, World Science Day for Peace and Development aims to ensure that citizens are kept informed of developments in science. It also underscores the role scientists play in broadening our understanding of the remarkable, fragile planet we call home and in making our societies more sustainable.

Learn more about World Science Day for Peace and Development on the UNESCO website

Image: World Science Day for Peace and Development 2020 poster

Credit: UNESCO

FIRST EXPERIMENTS ARE CARRIED OUT ON SIRIUS

The new Brazilian synchrotron light source, Sirius, from the Brazilian Synchrotron Light Laboratory (LNLS) at the Brazilian Center for Research in Energy and Materials (CNPEM), carried out the first experiments on one of its beamlines this week. The first research station to start operating, still in the commissioning stage, can reveal details of the structure of biological molecules, such as viral proteins. These first experiments are part of an effort by CNPEM to provide a cutting-edge tool to the Brazilian scientific community working in SARS-CoV-2 research.

In these initial analyses, CNPEM researchers observed crystals of a coronavirus protein, essential for the development of COVID-19. The first results reveal details of the structure of this protein, important for understanding the biology of the virus and supporting research that seeks new drugs against the disease.

>Read more on the LNLS website