The current global pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A critical initial step of infection is the interaction of the virus with receptors on host cells. In the case of SARS-CoV-2 and other coronaviruses, this receptor binding occurs through the spike (S) protein on the virus surface. Both SARS-CoV-2 and the related SARS-CoV, which caused an outbreak in 2003, bind to angiotensin-converting enzyme 2 (ACE2) on human cells. However, the observed differences in tissues that are infected by these two viruses (tropism) suggests that additional host factors may be involved. On pages 861 and 856 of this issue, Daly et al. (1) and Cantuti-Castelvetri et al. (2), respectively, show that the membrane protein neuropilin-1 (NRP1) promotes SARS-CoV-2 entry and explain how NRP1 interacts with the SARS-CoV-2 S protein. The results suggest the S protein–NRP1 interaction as a potential antiviral target.