The Role of SARS-CoV-2 Spike Protein in Long-term Damage of Tissues and Organs, the Underestimated Role of Retrotransposons and Stem Cells, a Working Hypothesis

Title:The Role of SARS-CoV-2 Spike Protein in Long-term Damage of Tissues and Organs, the Underestimated Role of Retrotransposons and Stem Cells, a Working Hypothesis

Volume: 24

Author(s): Mario G. Balzanelli, Reza Rastmanesh, Pietro Distratis, Rita Lazzaro, Francesco Inchingolo, Raffaele Del Prete, Van H. Pham, Sergey K. Aityan, Toai Tran Cong, Kieu C. D. Nguyen and Ciro Gargiulo Isacco*

Affiliation:

• 118 SET, Department of Pre-hospital and Emergency, SG Giuseppe Moscati Hospital, 74120 Taranto, Italy
• Department of Interdisciplinary Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy

Keywords: COVID-19, SARS-CoV-2, ZIKV, mRNA, RNAi, ncRNA, L1, retrotransposons, pluripotent multipotent stem cells

Abstract: Coronavirus disease-2019 (COVID-19) is a respiratory disease in which Spike protein from SARS-CoV-2 plays a key role in transferring virus genomic code into target cells. Spike protein, which is found on the surface of the SARS-CoV-2 virus, latches onto angiotensin-converting enzyme 2 receptors (ACE2r) on target cells. The RNA genome of coronaviruses, with an average length of 29 kb, is the longest among all RNA viruses and comprises six to ten open reading frames (ORFs) responsible for encoding replicase and structural proteins for the virus. Each component of the viral genome is inserted into a helical nucleocapsid surrounded by a lipid bilayer. The Spike protein is responsible for damage to several organs and tissues, even leading to severe impairments and long-term disabilities. Spike protein could also be the cause of the long-term post-infectious conditions known as Long COVID-19, characterized by a group of unresponsive idiopathic severe neuro- and cardiovascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Guillaume-Barret's like-disease. In this paper, we suggest a pervasive mechanism whereby the Spike proteins either from SARS-CoV-2 mRNA or mRNA vaccines, tend to enter the mature cells, and progenitor, multipotent, and pluripotent stem cells (SCs), altering the genome integrity. This will eventually lead to the production of newly affected clones and mature cells. The hypothesis presented in this paper proposes that the mRNA integration into DNA occurs through several components of the evolutionarily genetic mechanism such as retrotransposons and retrotransposition, LINE-1 or L1 (long interspersed element-1), and ORF-1 and 2 responsible for the generation of retrogenes. Once the integration phase is concluded, somatic cells, progenitor cells, and SCs employ different silencing mechanisms. DNA methylation, followed by histone modification, begins to generate unlimited lines of affected cells and clones that form affected tissues characterized by abnormal patterns that become targets of systemic immune cells, generating uncontrolled inflammatory conditions, as observed in both Long COVID-19 syndrome and the mRNA vaccine.

Cite this article as:

Balzanelli G. Mario, Rastmanesh Reza, Distratis Pietro, Lazzaro Rita, Inchingolo Francesco, Del Prete Raffaele, Pham H. Van, Aityan K. Sergey, Cong Tran Toai, Nguyen C. D. Kieu and Isacco Gargiulo Ciro*, The Role of SARS-CoV-2 Spike Protein in Long-term Damage of Tissues and Organs, the Underestimated Role of Retrotransposons and Stem Cells, a Working Hypothesis, Endocrine, Metabolic & Immune Disorders - Drug Targets 2024; 24 () . https://dx.doi.org/10.2174/0118715303283480240227113401