Viruses engage receptors on a host cell to initiate infection. Soluble versions of the receptors act as decoys that bind and block receptor-binding sites on the virus. However, human receptors often bind viruses weakly and in most cases also interact with endogenous factors in the human body as part of their normal physiology. These competitive off-target interactions adversely impact safety and efficacy. There is therefore an affinity and specificity problem that must be solved before soluble receptors can achieve their therapeutic potential. Orthogonal Biologics uses deep mutagenesis to resolve these challenges, engineering receptors that are orthogonal to normal human biology and with affinities that rival monoclonal antibodies. At this time, the company has lead biologic drug candidates for SARS-CoV-2 (the virus responsible for COVID-19) and human cytomegalovirus (the leading non-genetic cause of birth defects), as well as ongoing interests in zoonotic pathogens with pandemic potential and herpesviruses.
