Working Paper Review Version 1 This version is not peer-reviewed

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

Version 1 : Received: 1 May 2021 / Approved: 4 May 2021 / Online: 4 May 2021 (16:24:51 CEST)

A peer-reviewed article of this Preprint also exists.

Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, and Vladimir N. Uversky Journal of Proteome Research 2022 21 (4), 874-890 DOI: 10.1021/acs.jproteome.2c00001 Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, and Vladimir N. Uversky Journal of Proteome Research 2022 21 (4), 874-890 DOI: 10.1021/acs.jproteome.2c00001


SARS-CoV-2 was empirically and computationally found to be of a specific but peculiar evolution. Shell disorder models found that the outer shell (M protein) of SARS-CoV-2 to be among the hardest in its CoV family. The hard outer shell (low M percentage of disorder (PID)) is likely to be related to the SARS-CoV-2 resistance to the antimicrobial enzymes in saliva and mucus, and be responsible for the high-level of viral shedding which has been observed clinically. Experimental studies have also shown that SARS-CoV-2 is more resilient in the environment than many other CoVs, including SARS-CoV-1. Another aspect of the shell disorder models predicts that SARS-CoV-1 is more virulent than SARS-CoV-2 because of higher inner shell disorder (N PID) that helps SARS-CoV-1 replicate faster in vital organs despite being of lesser viral loads in the saliva and mucus, unlike SARS-CoV-2. This has been reaffirmed experimentally, where higher levels (50 folds) of infectious particles were detected in the SARS-CoV-1 samples in comparison with those of SARS-CoV-2. The hard outer shell of SARS-CoV-2 has been found to be associated with burrowing animals, particularly pangolins, which are often in contact with buried feces. For these reasons, the M protein is highly conserved among close relatives of SARS-CoV-2. The phylogenetic tree using M, unlike the genome-wide one, shows that pangolin-CoVs are more closely related to SARS-CoV-2 than bat-RaTG13. Previous phylogenetic studies may have been confused by recombinations that are usually poorly handled. According to the shell disorder models based on the N PID, an attenuated COVID-19 strain is likely to have entered humans via pangolins in 2017 or before, which provides the virus enough time to adapt to humans. This could explain why the SARS-CoV-2 S protein is highly adapted to the human ACE-2. The specific but peculiar evolution has a wide range of clinical, immunological, and epidemiological implications.


Pangolin; Intrinsic; Disorder; Protein; Nucleocapsid; Virulence; Shell; Covid; Coronavirus; Vaccine; Immune; Antibody; Shell; Nucleoprotein; Matrix; Attenuate; Severe Acute Respiratory


Medicine and Pharmacology, Pulmonary and Respiratory Medicine

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