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

Abstract

The basic tenets of the shell disorder model (SDM) as applied to COVID-19 are that the harder outer shell of the virus shell (lower PID—percentage of intrinsic disorder—of the membrane protein M, PIDM) and higher flexibility of the inner shell (higher PID of the nucleocapsid protein N, PIDN) are correlated with the contagiousness and virulence, respectively. M protects the virion from the anti-microbial enzymes in the saliva and mucus. N disorder is associated with the rapid replication of the virus. SDM predictions are supported by two experimental observations. The first observation demonstrated lesser and greater presence of the Omicron particles in the lungs and bronchial tissues, respectively, as there is a greater level of mucus in the bronchi. The other observation revealed that there are lower viral loads in 2017-pangolin-CoV, which is predicted to have similarly low PIDN as Omicron. The abnormally hard M, which is very rarely seen in coronaviruses, arose from the fecal–oral behaviors of pangolins via exposure to buried feces. Pangolins provide an environment for coronavirus (CoV) attenuation, which is seen in Omicron. Phylogenetic study using M shows that COVID-19-related bat-CoVs from Laos and Omicron are clustered in close proximity to pangolin-CoVs, which suggests the recurrence of interspecies transmissions. Hard M may have implications for long COVID-19, with immune systems having difficulty degrading viral proteins/particles.

Variant-Related Differences in Laboratory Biomarkers among Patients Affected with Alpha, Delta and Omicron: A Retrospective Whole Viral Genome Sequencing and Hospital-Setting Cohort Study

“…Even though currently little is known in this field, the differences in clinical manifestations by the various variants could be traced to the differences in SARS-CoV-2 protein structures. In an interesting study by Goh et al [ 14 ], it is mentioned that Omicron has a much lower N protein disorder than the other variants, which could account for its lower virulence as N is involved in rapid replication. While all VOCs have hard outer proteins (M) that could be responsible for long COVID, Omicron has among the hardest M proteins, which could be responsible for its higher D-dimer values since a harder M means that it will be more difficult for the immune system to degrade it.…”

SARS-CoV-2 Spike Protein Mutation at Cysteine-488 Impairs Its Golgi Localization and Intracellular S1/S2 Processing

“…The M protein, another SARS-CoV-2 viral protein, induces spike protein retention in the ERGIC and Golgi apparatus [ 1 , 16 ]. Another viral structural, protein N, is known to be responsible for COVID-19 virulence as it affects the rate of replication of the virus [ 22 ]. Interaction among the coronaviral structural proteins (N, E, S, and M), as well as a host membrane envelope obtained from the site of budding, is required for viral assembly [ 23 ].…”

A Comparative Experimental and Computational Study on the Nature of the Pangolin-CoV and COVID-19 Omicron

“…A fourth category, group D, was discovered when data pertaining to COVID-19 poured in [19,20,26,30]. This group consists of CoVs that have abnormally hard outer shells (i.e., their M proteins are characterized by low disorder content, low PID M ) that are usually associated with a burrowing animal host, such as rabbits and pangolin.…”

“…This group consists of CoVs that have abnormally hard outer shells (i.e., their M proteins are characterized by low disorder content, low PID M ) that are usually associated with a burrowing animal host, such as rabbits and pangolin. The association between burrowing animals and hard outer shell of the virus has to do with the necessity of the virus to persist in feces that could be buried for a long time until encountered by another host [18,25,26,30]. It is believed that CoVs in this category has both high fecal-oral and respiratory transmission potentials.…”

“…Upon inspection of the shell disorder, we were able to reproduce the mentioned observation of attenuation by detecting that the Omicron PID N was similar to that of Pang2017. A group of us published the corresponding results in 2022 [25,26,30]. The present study examines the computational and experimental data that are pertained to the peculiar relationships among pangolin-CoV, non-Omicron SARS-CoV-2, and Omicron.…”