Two recently published studies published in Science by Daly et al. 1 and Cantuti-Castelvetri et al. 2 identified neuropilin-1 (NRP1) as an additional cellular mediator which may facilitate the entry of the new severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 (SARS-CoV-2) into host cells. The findings of these elegant studies collectively indicate that, in addition to the role of angiotensin-converting enzyme 2 (ACE2) in mediating the cellular entry of SARS-CoV-2, NRP1 may act as a host cell mediator that can increase the infectivity and may thus contribute to the tissue/organ tropism of this coronavirus. SARS-CoV-2 is an enveloped RNA virus that is transmitted mainly via air droplets and causes a viral infectious disease, which was first described at the end of 2019 (ie, coronavirus disease 2019; COVID-19). 3 COVID-19 manifestations range from mild (asymptomatic or mild respiratory tract infection in most cases) to severe or even fatal in high-risk individuals, with respiratory and extra-pulmonary manifestations requiring hospitalization and potentially mechanical ventilation and intensive care unit (ICU) support. 3

As noted for the closely related SARS-CoV, SARS-CoV-2 entry into human cells is mediated by ACE2, which acts as a cell membrane receptor binding the spike (S1) glycoproteins on the surface of SARS-CoV-2 virions. 4 In addition, transmembrane protease serine 2 (TMPRSS2) and other proteases (eg, furin), which are located in the host cell membrane, secretory pathway and endocytic compartments, have also been shown to play a key role by priming the spike proteins of SARS-CoV-2 and facilitating its endocytosis and the release of its viral genome in the infected host cell for subsequent replication (Fig. 1 a). 4–6 Notably, ACE2 exhibits a low/moderate expression in the human respiratory system; thus, research has also focused on identifying additional mediators which may increase SARS-CoV-2 infectivity and may contribute to the tissue/organ tropism of this coronavirus (Fig. 1 b, c). 4, 5 Accordingly, data are emerging for a number of cellular mediators/receptors which may also facilitate the host cell infection by SARS-CoV-2, including CD147, glucoseregulated protein 78 (GRP78), angiotensin II receptor type 2 (AGTR2), the receptor for advanced glycation end products (RAGE), heparan sulfate, sialic acids and neuropilin-1 (NRP1). 4, 5