Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic and millions of deaths worldwide. It is in the family of betacoronaviruses, and like other RNA viruses, evolves quickly due to its high mutation rate. This makes SARS-CoV-2 especially difficult to combat, and to date, few effective treatments are available. SARS-CoV-2 replication relies on nonstructural protein 13 (nsp13), a superfamily 1 helicase. Because it is highly conserved across related viruses and essential for viral replication, nsp13 is an attractive therapeutic target. We have developed a nanopore tweezers assay which can resolve the 1 ms long, single-nucleotide steps taken by nsp13, revealing the motor’s mechanochemistry in exquisite detail. Using this assay, we investigate the mechanism of small molecule inhibitors and discuss implications for drug development and studying future viral helicases.
Boyer et al. (Sun,) studied this question.