A team of biologists from the International Biophysical Society reported the development of a longHR2_42 substance that appears to suppress all known variants of SARS-CoV-2. The researchers describe using a portion of the spike protein, the S-protein, from the coronavirus envelope as part of their approach. The findings were detailed in a publication appearing in the Proceedings of the National Academy of Sciences (PNAS).
The S-protein on living coronavirus particles comprises two regions, a short segment and a longer segment, which together form the mechanism the virus uses to gain entry into cells. The team synthesized a short-molecule analog designed to fit inside the S-protein and thereby hinder the virus’s ability to infect cells. A leading statement from a Stanford University researcher notes that this short analog binds within the S-protein to block the process that would normally permit infection.
The S-protein is the spike that protrudes from the virus’s membrane surface, enabling the virus to attach to and penetrate human and other mammalian cells. Because of this role, most vaccines target the S-protein to elicit protective immune responses. This strategic focus on the spike underlines why the new drug concept centers on disrupting the spike-driven entry pathway.
The therapeutic candidate targets the seventh power interaction between HR1 and HR2, a critical region of the spike apparatus involved in the virus’s entry into human cells. By guiding HR1 and HR2 to associate with a modified HR2 peptide, the compound appears to hinder viral replication within the body. The approach relies on an engineered interaction that interrupts the normal fusion sequence required for infection.
Importantly, the HR1HR2 region shows strong conservation as the virus evolves. Drugs that act on this portion tend to retain activity across multiple SARS-CoV-2 lineages, including those associated with the Omicron variant. This characteristic offers the potential for broad effectiveness even as the virus continues to mutate.
Currently, researchers are conducting experiments in mouse models infected with SARS-CoV-2 to evaluate safety and efficacy in vivo. The scientists also plan to explore delivery methods that could optimize the therapeutic potential. If the findings persist in preclinical testing, the next step would involve inhalation-based administration to deliver the drug directly to the respiratory tract, with the aim of reducing the severity of respiratory symptoms in future clinical scenarios.