How similar and different are SARS-CoV and SARS-CoV-2?
As viruses in the same lineage, SARS-CoV and SARS-CoV-2 are very similar (Table 1), sharing 82% nucleotide sequence homology [48]. Known interferon antagonists encoded by SARS-CoV include nsp1, nsp3, nsp16, ORF3b, ORF6, M and N proteins [49]. They, respectively, share 84, 76, 93, 32, 69, 91, and 94% amino acid sequence identity with their counterparts in SARS-CoV-2. Known activators of NLRP3 inflammasome encoded by SARS-CoV include E, ORF3a, and ORF8b [50]. They, respectively, share 95, 72, and 40% amino acid identity with their counterparts in SARS-CoV-2. It is noteworthy that some accessory proteins that modulate interferon response and inflammasome activation in the two viruses varied substantially. It will be of interest to see whether the divergence might have affected the virulence and pathogenicity of SARS-CoV-2.
Comparison of the sequence and genome organization of SARS-CoV and SARS-CoV-2 reveals more similarities than differences. Overemphasizing the differences in the initial stage of the outbreak has turned out to be counterproductive and very costly in disease control. The sequence similarities predict that the patterns and modes of the interaction between SARS-CoV-2 and host antiviral defence would be similar. Indeed, they share many features during the course of infection. First, they share the same cellular receptor ACE2 [35]. Second, their transmission routes and patterns are very similar. While both are transmitted through droplets primarily, close contact is a major risk factor. The attack rate of SARS-CoV-2 within the family context is even higher than that of SARS-CoV [36,51]. The faecal–oral route for transmission of SARS-CoV-2 has been reported as in the case of SARS-CoV. More studies are required to elucidate the exact role of faecal–oral transmission in the spreading of SARS-CoV-2. Third, superspreading events have been documented for SARS-CoV [52] and are also suspected to have occurred in the transmission of SARS-CoV-2, which could explain the rapid increase in confirmed cases in many places including 691 on the Diamond Princess cruise ship as of 23 February 2020. Fourth, clinical presentations of SARS-CoV and SARS-CoV-2 infection are similar, although symptoms associated with SARS-CoV-2 infection are generally milder. Fifth, host antiviral defence plays a critical role in the course of both SARS-CoV and SARS-CoV-2 infection. For severe cases, immunopathogenesis and induction of a proinflammatory cytokine storm are the culprit. Finally, drugs tested effective for SARS-CoV have been shown to exhibit an anti-SARS-CoV-2 effect; examples include nucleotide analogue Remdesivir [53], protease inhibitors Lopinavir and Ritonavir, as well as interferon α2a. Particularly, activation of innate antiviral response by interferon α2a should have beneficial effects at least in the initial stage of infection. However, cautions should still be observed and the possibility that interferon α2a might exacerbate inflammation during the late phase of SARS-CoV-2 infection cannot be excluded. Other innate immune stimulators should also be tested for anti-SARS-CoV-2 effects in future in vitro and in vivo experiments.