Scientists forge weapons for the fight against corona virus

Microscopic images help identifying the weak spots of our enemy: Corona virus

With the help of electron microscopy, scientists can identify the weak spot of corona virus. Konstantin Kolosov, Pixabay

One option in the fight against the corona virus (SARS-CoV-2) is the determination of its weak spots. Structural models can help to predict the effectiveness of already existing anti-viral drugs against the new pathogen. Such an attempt was published on 10.04.2020 by Chinese and Australian researchers in the scientific journal Science.

To date, approximately 160,000 people have died worldwide from the SARS-CoV-2. To this point, the virus is an over-powerful opponent and will remain to be, until we find a way to fight back. But the development and approval of a vaccine could take at least one more year. A faster solution would be the use of anti-viral drugs that are already on the market. These could at least dampen the symptoms of the COVID-19 disease and reduce death rates.

However, these existing drugs were developed to fight other viruses. They might be effective against corona as well, but perhaps to a lesser extent. Therefore, the drugs need to be tested, as it is done right now. But it would be better to have a way to foresee the potency of a medicine, before using it. Chinese and Australian scientists sought to predict the effectiveness of the anti-viral drug Remdesivir, by analyzing how well it could bind SARS-CoV-2’s structure in a computer model.

Knowing the structure of corona virus can help finding a drug against it.  

Graphic from PIRO4D, Pixabay

A virus has a simple architecture and yet, it consists of different parts with specific functions. Many scientists worldwide study the structure of SARS-CoV-2, to find its Achilles heel. They want to identify areas that could be targeted by anti-viral drugs. One possible weak spot is the virus’ propagation machinery: a protein complex that is vital for its replication. Anti-viral drugs, such as the agent against Ebola, Remdesivir, generally function by binding to the propagation machinery and thereby prevent viral replication.

Such a drug keeps the number of pathogens low and makes it easier for the body to deal with the invader. Thus, for a drug to work against SARS-COV-2, it is vital that it can bind the propagation complex with precision. The structures must be compatible like pieces of a puzzle. The team of Chinese and Australian scientists have made a detailed computer model, based on electron microscopy images. And they can use this model to test how well virtual molecules of Remdesivir can fit. And indeed, they found that the structures of the corona virus and the drug are a good match.

Remdesivir appears very promising in clinical trials too, therefore, using the modeling tool against corona is a proof of concept of this technique. But there is more that can be done with it: the core component of the replication machinery from SARS-CoV-2 is a complex that consists of multiple proteins. The researchers of the modeling study found that the complex resembles the replication machinery of SARS-CoV-1, the virus which caused the pandemic of 2002-2004. Though the structure of SARS-CoV-2 is a little more compact here and there, and has a small part sticking out. Overall, the complex also resembles other pathogens, such as the Polio virus, but with even more variation. These comparisons show that there are more possibilities for other drugs to bind, thus be effective against the COVID-19 disease. 

“The rapid global spread of COVID-19 virus has emphasized the need for the development of new coronavirus vaccines and therapeutics” 

Next steps

The Achilles heel of Corona is its reproductive system. And the model of it was published by the scientists who developed it, enabling even more researchers to use it in the search of other potential drug candidates. Even though Remdesivir seems promising, there may be even better agents available. And it is furthermore possible to make a potent cocktail out of multiple substances. This way, they could enhance each other, as it is known to be the case for a drug against HIV (Ritonavir) that positively influences an agent against Hepatitis C (Danoprevir). The knowledge of corona’s weak spot could even be used to specifically design molecules and use them as well fitted, potent medicine.

“The structure provides a basis for the design of new antiviral therapeutics (…).”

Much research is done in different directions and this will fill our armory with different weapons that we can use in the fight against corona virus.

Read more about the corona virus


References

  1. Gao, Y., Yan, L., Huang, Y., Liu, F., Zhao, Y., Cao, L., … & Ge, J. (2020). Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target. bioRxiv.
  2. https://www.spiegel.de/wissenschaft/medizin/corona-moeglicher-durchbruch-mit-medikament-remdesivir-a-52c07b75-4594-4b84-bfa9-877bfdf6dcbe                     article from 17.4.2020 1:49 p.m., written by Janne Kieselbach, viewed 17.4. 8:18 p.m
  3. Wang, M., Cao, R., Zhang, L., Yang, X., Liu, J., Xu, M., … & Xiao, G. (2020). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell research30(3), 269-271.
  4. https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/          article from 20.03.2020, written by Damian Garde, viewed 18.04.2020 12:45

Published by Katrin Heidemeyer

Katrin Heidemeyer ist Doktorandin im Bereich Biochemie an der Wageningen University and Research. Durch ihre Arbeit möchte sie das Wissen über die Spezifität von Hormon-Signalen in Pflanzen erweitern. Da ihre Interessen über Pflanzenbiologie hinausreichen, schreibt sie in ihrer Freizeit über diverse Themen. Von Ernährung zu Psychologie, der Neugierde sind keine Grenzen gesetzt.

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