ZINC PORTERS, AND THEIR MONOCLONAL ANTIBODY CONJUGATES, FOR THE PREVENTION AND TREATMENT OF COVID-19 (SARS-COV-2), OTHER INFECTIONS, AND CANCERS

摘要

The present invention describes how a MAh specific to a viral or cancer antigen can be linked to a novel Zn porting peptide that is engineered to load ionic Zn absent requirement for biological catalysis, carry Zn stably through the circulation, release payload proximal to diseased cells, deliver its Zn cargo intracellularly due to ionophore activity, and release Zn intracellularly. As specifically designed for COVID-19, the payload can be released by furin cleavage, and the Zn released intracellulary by cleavage at a 3CL major COVID protease site replacing sequences naturally found in alpha defensin-5, as one example, or by many other variations encompassing this design. The peptide's entry and intracellular Zn release can be further facilitated by the insertion of an arginine-lysine rich membrane translocation sequence at its amino or carboxyl terminus. The design provides a novel unifying strategy for preventing and treating COVID-19 (SARS-CoV-2) infection, other coronaviral infections, influenza infections, and many cancers.