Differences and similarities between SARS-CoV and SARS-CoV-2: spike receptor-binding domain recognition and host cell infection with support of cellular serine proteases

Abstract

Novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) became pandemic by the end of March 2020. In contrast to the 2002-2003 SARS-CoV outbreak, which had a higher pathogenicity and lead to higher mortality rates, SARSCoV-2 infection appears to be much more contagious. Moreover, many SARS-CoV-2 infected patients are reported to develop low-titer neutralizing antibody and usually suffer prolonged illness, suggesting a more effective SARS-CoV-2 immune surveillance evasion than SARS-CoV. This paper summarizes the current state of art about the differences and similarities between the pathogenesis of the two coronaviruses, focusing on receptor binding domain, host cell entry and protease activation. Such differences may provide insight into possible intervention strategies to fight the pandemic.

Keywords: Coronavirus; Furin; Receptor binding domain; Sars-CoV; Sars-CoV-2.

Fig. 1

a Coronaviruses structures. The membrane (M), envelope (E) and spike (S) structural proteins are anchored to the viral envelope which contains the ribonucleoprotein core, i.e., the nucleocapsid protein (N) which acts as a scaffold surrounding the single-stranded RNA. b The surface spike is composed by the S1 subunit, which harbors the receptor binding domain (RBD), and by the S2 subunit, the stem which anchors the spike to the viral envelope and, following protease activation, enables host cell fusion

Fig. 2

Receptor-binding domain (RBD) of the S protein may constantly switch between a “lying-down” and a “standing-up” position. In SARS-CoV-2, RBD is mostly in the “lying-down” position, a state associated with not only ineffective receptor binding, but also immune evasion. In SARS-CoV, RBD is mostly in “standing-up” position, a state associated with not only high effective receptor binding, but also immune recognition

Fig. 3

After initial binding of the ACE2 receptor, SARS-CoV spike is proteolytically activated and enzymatically cleaved at the S1/S2 level. S1 than dissociates from S2 and the truncated 2 subunit of the Spike protein facilitates fusion of viral and cellular membranes [28, 38]