hand holding syringe with yellow liquid

Image source: Unsplash/Diana Polekhina

SARS-CoV-2 medication

Remdesivir: additional mechanism against Covid-19 discovered

When a cell is infected, SARS-CoV-2 not only causes the host cell to produce new virus particles. The virus also suppresses host cell defence mechanisms. The virus protein nsP3 plays a central role in this.

Using structural analyses, researchers at Goethe University in cooperation with the Swiss Paul Scherrer Institute have now discovered that a decomposition product of the virostatic agent remdesivir binds to nsP3. This points to a further, previously unknown effective mechanism of remdesivir which may be important for the development of new drugs to combat SRS-CoV-2 and other RNA viruses.

The researchers published their findings in the ACS Medicinal Chemistry Letters.

The development of such medicines could also help prepare for future virus pandemics

Stefan Knapp

The virostatic agent remdesivir was developed to disrupt an important step in the propagation of RNA viruses, to which SARS-CoV-2 also belongs: the reproduction of the virus’s own genetic material. This is present as RNA matrices with which the host cell directly produces virus proteins. To accelerate the production of its own proteins, however, RNA viruses cause the RNA matrices to be copied. To do so, they use a specific protein of their own (an RNA polymerase), which is blocked by remdesivir. Strictly speaking, remdesivir does not do this itself, but rather a substance that is synthesized from remdesivir in five steps when remdesivir penetrates a cell.

In the second of these five steps, an intermediate is formed from remdesivir, a substance with the somewhat unwieldy name GS-441524 (in scientific terms: a remdesivir metabolite). GS-441524 is a virostatic agent as well. As the scientists in the group headed by Professor Stefan Knapp from the Institute for Pharmaceutical Chemistry at Goethe University Frankfurt have discovered, GS-441524 targets a SARS-CoV-2 protein called nsP3. nsP3 is a multifunctional protein, whose tasks include suppressing the host cell’s defence response. The host cell is not helpless in the face of a virus attack, but activates inflammatory mechanisms, among other things, to summon the aid of the cell’s endogenous immune system. nsP3 helps the viruses suppress the cell’s calls for help.

Professor Stefan Knapp explains: “GS-441525 inhibits the activities of an nsP3 domain which is important for the reproduction of viruses, and which communicates with human cellular defence systems. Our structural analysis shows how this inhibition functions, allowing us to lay an important foundation for the development of new and more potent antiviral drugs – effective not only against SARS-CoV-2. The target structure of GS-441524 is very similar in other coronaviruses, for example SARS-CoV and MERS-CoV, as well in a series of alphaviruses, such as the chikungunya virus. For this reason, the development of such medicines could also help prepare for future virus pandemics.” 


Source: Goethe University Frankfurt

11.05.2021

Read all latest stories

Related articles

Photo

Coronavirus prevention

Double vaccination cuts risk of Long Covid in half

Adults who have received a double vaccination are 49% less likely to have Long Covid should they contract a Covid-19 infection, according to new research from King's College London. The scientists…

Photo

Unexpected find

Anti-tapeworm drug shows promise against Covid-19

Researchers from the German Center for Infection Research (DZIF) at Charité – Universitätsmedizin Berlin and the University of Bonn have examined the way in which SARS-CoV-2 reprograms the…

Photo

Medication testing

'Airway-on-a-chip' to find new Covid-19 drugs

A collaboration spanning four research labs and hundreds of miles has used the organ-on-a-chip (Organ Chip) technology from the Wyss institute at Harvard Univesity to identify the antimalarial drug…

Related products

Alsachim, a Shimadzu group company – Dosimmune

Clinical Chemistry

Alsachim, a Shimadzu group company – Dosimmune

Alsachim, a Shimadzu Group Company
Analyticon Biotechnologies AG - Urilyzer 100 Pro

Urinalysis

Analyticon Biotechnologies AG - Urilyzer 100 Pro

Analyticon Biotechnologies AG
Beckman Coulter – Access Interleukin-6 (IL-6)

Immunoassays

Beckman Coulter – Access Interleukin-6 (IL-6)

Beckman Coulter, Inc.
Beckman Coulter – AU5800 Series

Clinical Chemistry

Beckman Coulter – AU5800 Series

Beckman Coulter, Inc.
Beckman Coulter – DxC 700 AU

Clincal Chemistry

Beckman Coulter – DxC 700 AU

Beckman Coulter, Inc.
Beckman Coulter – HbA1c Advanced

Clinical Chemistry

Beckman Coulter – HbA1c Advanced

Beckman Coulter, Inc.
Subscribe to Newsletter