Scientists at Stanford University, the University of California and Harvard Medical School have created a molecule based on part of the spike protein (S-protein) that attaches to the virus and prevents SARS-CoV-2 from fusing with an infected host cell. This is reported in an article published in the journal Proceedings of the National Academy of Sciences (PNAS).
To infect a cell, the viral spike S protein must bind to the cellular receptor ACE2. Antiviral drugs of various classes inhibit this binding, preventing the spread of infection. They include peptide inhibitors that block the formation of a bundle of six protein helices involving specific S-protein motifs, the so-called heptad repeats 1 and 2 (HR1HR2). This prevents the viral membrane from fusing with the cell membrane.
The new longHR2_42 inhibitor is a modified HR2 peptide that interacts with the HR1 triple helix, thereby blocking the formation of a six-stranded bundle. The drug targets a part of the virus that remains almost unchanged during evolution, so it should be effective against various strains of SARS-CoV-2, including omicron variants.
Scientists are currently testing the inhibitor in mice infected with SARS-CoV-2. It is expected that the drug can be administered by inhalation so that it enters the respiratory tract at an early stage of infection, which will prevent severe respiratory symptoms.
Other treatments for COVID-19 rely on drugs that attach to the outside of the spike protein. For example, bebtelovimab targets the part of the S protein that has mutated over time, so it doesn’t work against new variants of COVID-19.