Programming designer DNA nanostructures for inhibition of virus infection

Abstract

The challenges underlying current coronavirus disease 2019 treatment and rapid diagnostic development are already well known from previous encounters with newly emerging pathogens (e.g., the 2009 H1N1 pandemic 1,2). Inhibition and treatment of virus infections typically relies on neutralizing antibodies (NAbs) that target virus surface-specific epitopes mainly in a one-to-one fashion 3. Production of NAbs can be triggered by vaccination or active virus infection in the host. However, safe and effective vaccines normally take years to develop for an emerging virus. Therapeutic antibodies can be administered in response to viral infections. However, producing antibodies for treatment is very costly and time consuming. Importantly, NAbs may induce unwanted antibody-dependent enhancement of infection 4,5 (for example, with dengue virus (DENV) vaccine), where antibodies induce increased viral infectivity in vivo. Viruses present unique spatial patterns of antigens on their surfaces 6. Such patterns facilitate multivalent binding of the virus to host cells for enhanced pathogenic infectivity. Based on this naturally occurring multivalent virus-cell binding mechanism, creating polyvalent virus entry blockers is a promising and practical approach to producing potent inhibitors of virus infections.