Computational, Experimental, and Clinical Evidence of a Specific but Peculiar Evolutionary Nature of (COVID-19) SARS-CoV-2

Abstract

The shell disorder models have predicted that SARS-CoV-2 is of a specific but peculiar evolutionary nature. All coronaviruses (CoVs) closely related to SARS-CoV-2 have been found to have the hardest outer shells (M protein) among CoVs. This hard shell (low M percentage of intrinsic disorder (PID)) is associated with burrowing animals, for example, pangolins, and is believed to be responsible for the high contagiousness of SARS-CoV-2 because it will be more resistant to antimicrobial enzymes found in saliva/mucus. Incoming clinical and experimental data do support this along with a prediction based on another aspect of the shell (N, inner shell) disorder models that SARS-CoV-1 is more virulent than SARS-CoV-2 because SARS-CoV-2 produces fewer virus copies in vital organs even if large amounts of infections particles are shed orally and nasally. A phylogenetic study using M reveals a closer relationship of SARS-CoV to pangolin-CoVs than the bat-RaTG13 found in Yunnan, China. Previous studies may have been confused by recombinations that were poorly handled. The shell disorder models suggest that a pangolin-CoV strain may have entered the human population in 2017 or before as an attenuated virus, which could explain why SARS-CoV is found to be highly adapted to humans.

Insights on the evolution of Coronavirinae in general, and SARS-CoV-2 in particular, through innovative biocomputational resources

“…After phylogenetic genome-wide analysis, most studies indicated that Rhinolophus bats may be the natural host of the novel coronavirus ( Ma et al, 2021 ). However, these results should be critically appraised since classic dichotomic phylogenetic tools do not handle recombination well and results could be misleading if recombination occurs ( Goh et al, 2022 ; Posada, 2000 ). In order to deal with these constraints, Goh et al (2022) suggest narrowing the phylogenetic analysis to conserved proteins such as the M protein.…”

“…However, these results should be critically appraised since classic dichotomic phylogenetic tools do not handle recombination well and results could be misleading if recombination occurs ( Goh et al, 2022 ; Posada, 2000 ). In order to deal with these constraints, Goh et al (2022) suggest narrowing the phylogenetic analysis to conserved proteins such as the M protein. In doing so, a different tale emerges and pangolin is no longer so easily dismissed as ancestor.…”

“…This sequence is similar by convergence to the pangolin-CoV-2020; (2) A chimeral origin in which the backbone of the novel virus comes from RaTG13 and the RBD comes from the pangolin-Cov-2020. Interestingly, using an analytic strategy based on shell disorder models, Goh et al (2020) , Goh et al (2022) offered a renewed view that went against the mainstream on the subject. They measured the percentage of intrinsic disorder of proteins from the viral inner and outer shells, and suggested a silent spreading among humans of a SARS-CoV-2 precursor coming from pangolins.…”

A Study on the Nature of SARS-CoV-2 Using the Shell Disorder Models: Reproducibility, Evolution, Spread, and Attenuation

“…This enigma assumes that Omicron is a descendant of Wuhan-Hu-1. Some of our previous papers showed that this assumption may not be correct [ 21 , 22 ]. Additionally, many of the mutations seen in Omicrons are different from all other variants.…”

“…Others believe that it has been hiding in animals, such as mice. We have previously reported that our shell disorder models (SDMs) provide evidence that a burrowing animal, such as pangolins, could provide the optimal environment for the virus to incubate and evolve into a milder but more transmissible variant [ 21 , 22 ]. We will see that SDMs have specific answers or hints to many of the mysteries set forth.…”