New HR1 mimetic polypeptides for COVID-19 prevention, treatment, and diagnosis through the development of vaccines, drugs, and diagnostic methods.
New polypeptides to prevent, treat and diagnose SARS-CoV-2 coronavirus infection have been developed. These are short sequences that mimic fragments of the HR1 region, highly conserved, and that have a high affinity for HR2, being able to inhibit the fusion of viral and cellular membranes. They are ideal components for developing new vaccines, drugs, and diagnostic methods.
Coronavirus SARS-CoV-2 disease (COVID-19) has become the most severe pandemic in the last decades, causing huge human and economic losses. Despite the high research activity around it, the immunity granted by current vaccines decreases after several months, and new variants of the virus constantly appear that escape vaccine protection. In addition, no antiviral drugs exist to treat the infection.
Current vaccines are based on immunization with the complete inactivated virus; with the complete spike protein (S) using vectors, RNA, or DNA with or without mutations; or with the receptor-binding domain (RBD), from the S1 subunit of the spike protein. However, S1 regions are more variable than the S2 subunit, which is conserved even between different coronaviruses, and not so many mechanisms aimed at neutralizing it are currently known.
The S2 subunit features two regions HR1 and HR2 which interact during the cellular and viral membrane fusion process. This subunit is homologous to the transmembrane gp41 subunit from VIH, which is already demonstrated as an effective target to neutralize this virus.
Taking advantage of the high conservation of the S1 subunit and its homology with the gp41 subunit from VIH, new mimetic polypeptides from the HR1 region of the S2 subunit have been developed. Those polypeptides allow blocking membrane fusion with SARS-CoV-2 by interfering in the conformational change of HR1 and HR2 during this process.
These HR1 mimetic polypeptides show high thermal stability, are highly soluble, and can form high-affinity complexes with HR2. Their characteristics are ideal to prevent, treat and diagnose the infection caused by a coronavirus.