Camel VHH Nanobodies Bind the S2 Subunit of SARS-CoV-2 and Broadly Neutralize Variants including Omicron

Since its emergence in 2019, COVID-19 infected over 600 million people and over 6 million people have died from the disease. COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Neutralizing antibodies have been developed to bind to the receptor binding domain (RBD) on the spike (S) protein. Blocking the interaction of the RBD and the ACE2 receptor, is critical in neutralizing the virus. However, the S2 subunit, is also critical for viral infection and entry into human cells. The S2 subunit is highly conserved across many coronaviruses, however, there are currently no effective antibodies targeting this S2 subunit.

The inventors isolated the J1B4 camel VHH nanobody, a potent S2 binder that can neutralize all the known variants of SARS-CoV-2, including omicron. The J1B4 VHH can be engineered with other COVID binders to create multi-specific drugs to treat current COVID-19 infections as well as future SARS-like viral infections. This technology presents a promising novel treatment for SARS-CoV-2 infection by using the anti-S2 nanobodies alone or in combination with anti-S1/RBD nanobodies. 

The NCI seeks research co-development partners and/or licensees to further develop this nanobody as a possible treatment of COVID-19 infections.

Competitive Advantages:

• No currently available therapeutic antibodies targeting the S2 subunit of SARS-CoV-2
• Potential treatment for current and future SARS-CoV-2 infections
• Use of nanobodies suitable for developing non-invasive treatments, such as an intranasal spray

Commercial Applications:

• Treatment of SARS-CoV-2 infections
• Multi-specific antibody therapy
• Delivery of nanoparticles
• Diagnostic reagents for in vivo virus imaging
• Antiviral nanobody nasal spray