Novel antiviral therapeutics target SARS-CoV-2 infections

Remdesivir is currently the only FDA-approved drug for treating COVID-19. While remdesivir improves recovery time, it does not significantly reduce death rates in hospitalized adults. Researchers at the University of Kansas have produced novel antivirals that shows promise as a COVID-19 treatment.

The new antivirals target the conserved and essential RNA sequences in the SARS-CoV-2 viral genome. Specifically, the antivirals selectively bind to RNA secondary structures close to the start codon region in the viral genome, thereby inhibiting viral replication of SARS-CoV-2. In addition to their use as single agent inhibitors of SARS-CoV-2 replication, the antivirals can also be part of a bifunctional small molecule. A bifunctional small molecule typically includes a “guide arm” and an “effector arm.” The new antivirals act as the guide arm that binds to SARS-CoV-2 in order to target the effector arm to the virus, which ultimately results in enzymatic degradation of the virus. Accordingly, these novel antivirals can inhibit viral replication of SARS-CoV-2 and degrade the SARS-CoV-2 virus when used as part of a bifunctional small molecule.

Most drugs currently contemplated for treatment of COVID-19 target viral proteins. For example, remdesivir inhibits the SARS-CoV RNA-dependent RNA polymerase. The antivirals of the present technology target the RNA structural elements in the viral genome instead of the viral proteins of SARS-CoV-2. Accordingly, they can synergistically inhibit viral replication with drugs that target viral proteins, including remdesivir, thereby improving outcomes in COVID-19 patients compared to those treated with remdesivir alone.