Information on molecular tools shared between coronaviruses could provide a potential target for COVID-19

Coronaviruses exploit our cells so that they can copy themselves inside us. Once they enter our cells, they use our cellular machinery to make their own unique tools that help them generate these copies. By understanding the molecular tools shared between coronaviruses, it is possible to develop treatments that may not only work in the current COVID-19 pandemic, but also in future coronavirus outbreaks.

Rockefeller University researchers in the laboratories of Tarun Kapoor and Shixin Liu, including postdoctoral associate Keith Mickolajczyk, recently published their study on one of these molecular tools, which is a potential target for drugs. They will present their research on Tuesday, February 23 at the 65th Annual Meeting of the Biophysical Society.

During a viral infection, viruses make copies of themselves inside their host, and viruses carry genetic instructions for several tools to do so. One of these tools is called a helicase; all organisms have helicases that unwrap 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 to a helicase encoded in the genome of SARS-CoV-2 (the virus that causes COVID-19), called nsp13.

Mickolajczyk and his colleagues studied the mechanism that individual molecules of nsp13 use to unwind genetic material, and their study marks the first single-molecule unwinding experiments ever performed on a coronavirus helicase. They found that nsp13 is a relatively weak helicase, which means that it needs the assistance of mechanical forces to be activated, and that other viral molecules can help it. They also found that nsp13 did not act as a hepatitis C virus helicase with a similar shape, but rather acted as ring-shaped helicases found in bacteriophages (viruses that infect bacteria).

Because coronaviruses have helicases that are very similar to nsp13, it’s interesting to understand how this molecule works.

If we can come up with viral therapies that affect nsp13, we can have a first line of defense when new coronaviruses can potentially erupt and cause new epidemics or pandemics in the future. Understanding this mechanism now can help us design inhibitors that can be treatments for coronaviruses ”,

Keith Mickolajczyk, Postdoctoral Fellow, Rockefeller University

Their results, Mickolajczyk says, can provide information that can be exploited for drug discovery efforts. By inhibiting nsp13, a drug could prevent coronaviruses from reproducing, thereby stopping infections and stopping or preventing a pandemic.