A device encoded in coronaviruses provides a potential target for COVID-19

IMAGE: Nsp13 helicase (orange) releases RNA (blue), the same substance as the SARS-CoV-2 genome. Recent findings show that mechanical forces (black arrows) increase the efficiency of nsp13 disconnection. view more

Credit: Image courtesy of Keith Mickolajczyk.

ROCKVILLE, MD – Coronaviruses take advantage of our cells so they can replicate themselves inside us. Once they enter our cells, they use our cellular devices to make their own unique devices that help them generate these copies. By understanding the molecular mechanisms shared across coronaviruses, there is potential to develop therapies that can not only work in the conventional COVID-19 epidemic, but in our future coronavirus outbreaks as well. Rockefeller University researchers in the laboratory of Tarun Kapoor and Shixin Liu, including postdoctoral companion Keith Mickolajczyk, recently published their study of one of these molecular devices, which is a target potential drugs. They will present their research on Tuesday, February 23rd at the 65th Annual Meeting of the Biophysical Society.

During a viral infection, viruses replicate themselves within their host, and viruses carry genetic instructions for a number of devices to do so. One of these devices is called a helicase – every organism has helicases that carry the genetic information so that it can be read or copied. Mickolajczyk had been studying helicases and other molecular motors when the COVID-19 pandemic struck and turned his attention to a helicase encoded in the SARS-CoV-2 genome (the virus that causes COVID-19), called nsp13.

Mickolajczyk and his colleagues studied the technique used by individual nsp13 molecules to release genetic material, and their study marks the first single-molecular detachment experiments performed. ever made on coronavirus helicase. They found that nsp13 is a relatively weak helicase, meaning it needs to help mechanical forces to be activated, and can help other viral molecules. They also found that nsp13 did not function as a similarly shaped Hepatitis C virus helicase, and instead were more similar to ring-shaped helicases found in bacteriophages (bacteria-affecting viruses).

Because coronaviruses have helicases that are very similar to nsp13, it is valuable to understand how this molecule works. “If we can come up with a therapeutic treatment that has hit nsp13, we can have the first line of defense when new coronaviruses could explode and cause new epidemics or pandemics in the future. Understanding the method can This work is now helping us to design potential protective agents against coronaviruses, “Mickolajczyk says.

Their findings, Mickolajczyk says, may provide insights that can be extracted for drug detection efforts. By blocking nsp13, a drug may prevent coronaviruses from replicating themselves, thus preventing infections and stopping or preventing pandemic infection. spread.

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