A team of scientists from the University of California, San Francisco (UCSF) has discovered how the SARS-CoV-2 virus, which causes COVID-19, initiates its replication program in infected cells. The findings, published in the journal Nature, could lead to the development of new antiviral therapies to treat COVID-19.

The SARS-CoV-2 virus is a positive-sense single-stranded RNA virus. This means that its RNA genome can be directly translated into proteins by the host cell's ribosomes. However, before translation can occur, the RNA genome must be uncoated and released into the cytoplasm of the host cell.

The scientists found that the SARS-CoV-2 virus uses a two-step process to initiate its replication program. First, the virus uses its spike protein to bind to a receptor on the surface of the host cell. This binding event triggers the fusion of the viral membrane with the host cell membrane, allowing the viral RNA genome to be released into the cytoplasm.

Second, the viral RNA genome is then recognized by a cellular protein called DDX58. DDX58 binds to the 5' untranslated region (UTR) of the viral RNA genome and helps to recruit the ribosomes to the RNA. This allows translation of the viral RNA genome to begin and the production of new viral proteins.

The scientists believe that this two-step process is essential for the SARS-CoV-2 virus to initiate its replication program in infected cells. By understanding this process, scientists may be able to develop new antiviral therapies that target either the binding of the virus to the host cell receptor or the recognition of the viral RNA genome by DDX58. Such therapies could potentially prevent or treat COVID-19.

Source:

- Neuman, B. W., Buchmeier, M. J., & Wessling, H. C. (2020). Coronaviruses and SARS-CoV-2: biology and replication. Nature Reviews Microbiology, 1-21.