A team led by researchers at the University of Texas Southwestern Medical Center (UTSW) has determined how the new coronavirus builds an RNA "cap" that is critical to the virus's successful replication. The new findings, published in the journal Nature, are expected to lead to new strategies to combat COVID-19.
Study leader Dr. Vincent Taliablache said that if drugs targeting this protein domain could be developed and manufactured to inhibit RNA cap formation, it could provide a completely new approach to treating Covid-19.
The new coronavirus uses the genetic molecule RNA (ribonucleic acid) to provide instructions to infected host cells to build more copies of the virus. Dr. Thalia Bracchi explained that the molecular cap at one end of the viral RNA has multiple functions to achieve this. It hides the RNA from detection by the host cell's immune system, protecting the RNA from exonuclease or cellular enzymes that degrade it. At the same time, the molecular cap can also recruit cytokines that make viral proteins. If the virus loses this RNA cap, these processes stop and the infection does not continue.
This study shows that the SARS-CoV-2 NiRAN domain, part of a viral protein called nsp12, is involved in RNA cap synthesis. The NiRAN domain is a pseudokinase. The experiments showed that the NiRAN domain transfers viral RNA to another SARS-CoV-2 protein called nsp9, thereby producing an RNA-protein intermediate critical for cap formation.
Dr. Thalia Bracchi said he and his colleagues are working on ways to block the function of the NiRAN domain of SARS-CoV-2, which could eventually lead to a new class of drugs to fight Covid-19.
"In the long-term fight against the epidemic, we need antiviral drugs that target different parts and aspects of the virus life cycle," he said. "Adding a 'cap' inhibitor would be a good addition to the 'arsenal'. "
(Original title "Discovery of Important Mechanisms of New Coronavirus Replication [International War "Epidemic" Action]")