the N disorder range of pangolin-CoVs, not bat-CoVs, more closely matches that of SARS-CoV-2, especially when Omicron is included. The low N disorder (i.e., low content of intrinsically disordered residues in the nucleocapsid (N) protein), first observed in pangolin-CoV-2017 and later in Omicron, is associated with attenuation according to the Shell-Disorder Model. Our experimental study revealed that pangolin-CoV-2017 and SARS-CoV-2 Omicron (XBB.1.16 subvariant) show similar attenuations with respect to viral growth and plaque formation. Subtle differences have been observed that are consistent with disorder-centric computational analysis.
https://www.mdpi.com/1422-0067/25/14/7537
Interestingly, two sets of pangolin-CoV samples obtained were found to have approximately 90% similarities to SARS-CoV-2 [7,8,9]. One set was obtained from smuggled pangolins confiscated in Guangdong (GD) province in 2019. The other samples were also from smuggled pangolins but from Guangxi (GX) province (2017–2018) [7,8,9,10].
Likewise, SARS-CoV-2 was more efficiently attenuated because it is likely to have been passed between humans and pangolins for at least several years before the appearance of Wuhan-Hu-1 [15]. This is likely also the case in Omicron [19,32]. Further evidence of interspecies transmissions can be found in the facts that SARS-CoV-2 is capable of infecting a large number of mammalian species [54] and that bats often dwell alongside pangolins in caves and underground burrows [55].
The lower virulence of SARS-CoV-2 leads us to believe that the virus may have been incubating in an intermediary involving a burrowing animal, such as pangolin, for a relatively longer period of time.
Indeed, at least one laboratory has noticed that portions of the S proteins of pangolin-CoVs resemble most closely those of the SARS-CoV-2 S protein.
To jump to the conclusion, however, that SARS-CoV-2 came directly from bats would be to ignore the probability that SARS-CoV-2 had been moving to and fro between pangolins and humans for a long time. We have further evidence of this. The seemingly greater genetic difference in the pangolin-CoVs thus found may be a reflection of the greater diversity of pangolin-CoVs. In fact, the diversity in N disorder of SARS-CoV-2 more closely resembles that of pangolin-CoVs, not bat-CoVs.
https://link.springer.com/article/10.1186/s12915-024-02074-x
Early in the coronavirus disease 2019 (COVID-19) pandemic, Sunda pangolins (Manis javanica) involved in the illegal wildlife trade in mainland China were identified as hosts of severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs).
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