Entry, egress and vertical transmission of SARS-CoV-2

Abstract

The high infectivity and pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused the COVID-19 outbreak, one of the most devastating pandemics in more than a century. This pandemic has already left a trail of destruction, including enormous loss of life, a global economic slump, and widespread psychological damage. Despite assiduous world-wide endeavors, an effective cure for COVID-19 is still lacking. Surprisingly, infected neonates and children have relatively mild clinical manifestations and a much lower fatality rate than elderly adults. Recent studies have unambiguously demonstrated the vertical transmission of SARS-CoV-2 from infected pregnant women to fetuses, which creates yet another challenge for disease prevention. In this review, we will summarize the molecular mechanism for entry of SARS-CoV-2 into host cells, the basis for the failure of the lungs and other organs in severe acute cases, and the evidence for congenital transmission.

Keywords: ACE2; COVID-19; SARS-CoV-2; TMPRSS2; placental transmission.

Figure 1

Schematic illustration of the replication cycle of SARS-CoV-2. The entry of SARS-CoV-2 into host cells starts with the binding of S proteins with the receptor ACE2. The host cell surface protease TMPRSS2 activates S protein, which triggers fusion of the viral and host plasma membranes. SARS-CoV-2 can also enter the cell via endocytosis. In this pathway, the fusion of viral and lysosomal membranes is triggered by cathepsins. The autoproteolytic cleavage of viral polyproteins pp1a and pp1ab generates 16 Nsps with various functions. The RTCs anchor on DMVs, which appear to originate from the ER. The viral RNAs are stored in DMVs and transported to the cytosol for translation or viral assembly via double-membrane–spanning pores. Viral particles are assembled in the ER and/or ERGIC. The virions traffic to late endosomes/lysosomes and egress via the lysosomal exocytosis pathway.