Clues to Long COVID Linked to Virulence and Infectivity Found in Shell Proteins

TL;DR

The study suggests that the structure of SARS-CoV-2's shell proteins may explain its high infectivity and link to long COVID.

Contribution

The novel contribution is linking shell protein disorder to SARS-CoV-2's infectivity and long-term effects through computational and clinical evidence.

Findings

Abnormally hard M shell proteins in SARS-CoV-2 increase infectivity by resisting antimicrobial enzymes.

Lower disorder in the N shell correlates with reduced virulence compared to SARS-CoV-1.

Hard M proteins may allow the virus to hide in phagocytes, potentially causing long COVID.

Abstract

What are the main findings?
The abnormally hard M, detected among all SARS-CoV-2 viruses using AI, is believed to be the cause of SARS-CoV-2 high infectivity as it is more resistance to salivary and mucosal antimicrobial enzymes and, thereby, forces the infected person to shed much greater quantities of viral particles.N disorder could modulate the severity of COVID-19 and long COVID by allowing faster replication of the virus as correlations between the inner shell (N) disorder and virulence have been found.

The abnormally hard M, detected among all SARS-CoV-2 viruses using AI, is believed to be the cause of SARS-CoV-2 high infectivity as it is more resistance to salivary and mucosal antimicrobial enzymes and, thereby, forces the infected person to shed much greater quantities of viral particles.

N disorder could modulate the severity of COVID-19 and long COVID by allowing faster replication of the virus as correlations between the inner shell (N) disorder and virulence have been found.

What are the implications of the main findings?
Current knowledge of physiology, immunology and biochemistry suggests that the unusually hard M is not just associated with infectivity but also long COVID as the virus could resist the antimicrobial enzymes in the phagocyte and is thus able to dwell in it, which could become a virus reservoir.An understanding of the mechanisms by which the virus hides in the body, could lead to better treatments of long COVID by targeting the reservoir via antiviral drugs or correctly timed vaccination using the appropriate vaccine version.

Current knowledge of physiology, immunology and biochemistry suggests that the unusually hard M is not just associated with infectivity but also long COVID as the virus could resist the antimicrobial enzymes in the phagocyte and is thus able to dwell in it, which could become a virus reservoir.

An understanding of the mechanisms by which the virus hides in the body, could lead to better treatments of long COVID by targeting the reservoir via antiviral drugs or correctly timed vaccination using the appropriate vaccine version.

Clinical, experimental, and computational evidence of COVID-19 virulence and infectivity has been linked to SARS-CoV-2 shell disorder. A strong link was first discovered using an AI disorder-predicting tool, which detected an unusually hard (low disorder) outer shell among all SARS-CoV-2-related viruses but not in the 2003 SARS-CoV-1. This could account for the high infectivity found in SARS-CoV-2—but not in SARS-CoV-1—as it is believed that hard shells protect viral particles from the onslaught of the antimicrobial enzymes present in the respiratory system and saliva. As a result, much larger quantities of particles are shed by COVID-19 patients. Abnormally hard outer shells (M) are associated with burrowing animals, e.g., pangolins, and SARS-CoV-2 likely acquired these shells due to its long-term evolutionary interactions with pangolins. As for virulence, the inner shell of SARS-CoV-2 (N) has been found to exhibit lower disorder than that of SARS-CoV-1. This lower disorder is consistent with the fact that SARS-CoV-2 is less virulent than SARS-CoV-1, as higher disorder in the inner shell is associated with more efficient protein–protein binding during replication. The link between N/M disorder and virulence or infectivity falls under the umbrella of shell disorder models (SDMs), which can connect virulence, infectivity, and long COVID under one coherent concept. Evidence of the reliability and reproducibility of SDMs as applied to COVID-19 is examined. The hard M that is resisting the antimicrobial enzymes in the respiratory system can be extended to immunological enzymes, especially those found in phagocytes such as macrophages, which can therefore become a reservoir for the virus.

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