¿ES EL SARS-Cov-2 UN VIRUS ONCOGÉNICO?

Is #SARS-CoV-2 an #oncogenic #virus? - #JournalofInfection https://t.co/vaJVAEqUP7 #AlbertoGómezCarballa#FedericoMartinónTorres#AntonioSalas#GENVIP, Instituto de Investigación Sanitaria de Santiago, #Universidade de #SantiagodeCompostela, Santiago de Compostela, #Spain

— Guillermo Ruiz Zapatero (@ruiz_zapatero) October 31, 2022

Recently, in this journal, Wu et al. (1) and Gao et al. (2) have both indicated that host genetic variation related to COVID-19 might be associated to endometrial cancer. We here add evidence from gene expression analysis supporting that the connection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cancer could be more general, in line with several other viral infections that represent serious risks for carcinogenesis in humans. The SARS-CoV-2 has developed similar strategies to Epstein-Barr virus (EBV) and hepatitis B virus (HSV1) to control p53 by hijacking the protein via virus antigens, and ultimately leading to its degradation (3,4). Specifically, the Nsp2 viral protein of the SARS-CoV-2 interacts with the prohibitin 1 and 2 (PHB1, PHB2) that are primarily located in the mitochondrion and play an essential role in maintaining mitochondrial DNA activity. Their depletion triggers a chain of cell responses that lead to a leakage of reactive oxygen species (ROS) to the nucleus and oxidative damage, that ultimately provokes the impairment of the transactivation of p53-dependent genes. In addition, the Nsp3 SARS-CoV-2 protein binds and activates the RING finger and CHY zinc finger domain-cotainin protein 1 (RCHY1) and E3 ubiquitin ligase, promoting p53 degradation (5). Therefore, SARS-CoV-2 has the ability to trigger external and internal apoptotic pathways of the host cells, facilitating its spread. Impairment of p53 could be seen as a strategy of the virus to take advantage of the cell pathways controlled by this protein for its own benefit during acute phase of infection, therefore evading host immune response and facilitating its replication (3). In this context, a reduced expression of p53 during the acute phase of infection is also a biomarker of severe disease.

Although it has not been demonstrated yet, it has been hypothesized that a long-term inhibition of p53 by the SARS-CoV-2 could be carcinogenic. The onco-suppressive protein p53 is a key player within the apoptotic signaling pathway and regulates the expression of about 500 target genes; therefore, it plays a role in cell cycle arrest, cell aging, cell death, etc. (6). We examine three gene expression datasets to demonstrate that p53 is downregulated during acute SARS-CoV-2 infection and long coronavirus-disease 19 (COVID-19); a long-term reduction of p53 could be interpreted as a risk factor in carcinogenesis.

LA HUELLA DE ENDONUCLEASA INDICA UN ORIGEN SINTÉTICO DEL SARS-Cov-2 (I)

Endonuclease fingerprint indicates a #syntheticorigin of #SARS-CoV-2 https://t.co/9CkKNFredV

SARSCOV2 contains a peculiar pattern of unique restriction endonuclease recognition sites allowing efficient dis- and re-assembly of the viral genome characteristic of synthetic viruses

— Guillermo Ruiz Zapatero (@ruiz_zapatero) October 22, 2022

Abstract 

 To prevent future pandemics, it is important that we understand whether SARS-CoV-2 spilled over directly from animals to people, or indirectly in a laboratory accident. The genome of SARS-COV-2 contains a peculiar pattern of unique restriction endonuclease recognition sites allowing efficient dis- and re-assembly of the viral genome characteristic of synthetic viruses. Here, we report the likelihood of observing such a pattern in coronaviruses with no history of bioengineering. We find that SARS-CoV-2 is an anomaly, more likely a product of synthetic genome assembly than natural evolution. The restriction map of SARS-CoV-2 is consistent with many previously reported synthetic coronavirus genomes, meets all the criteria required for an efficient reverse genetic system, differs from closest relatives by a significantly higher rate of synonymous mutations in these synthetic-looking recognitions sites, and has a synthetic fingerprint unlikely to have evolved from its close relatives. We report a high likelihood that SARS-CoV-2 may have originated as an infectious clone assembled in vitro. 

Lay Summary To construct synthetic variants of natural coronaviruses in the lab, researchers often use a method called in vitro genome assembly. This method utilizes special enzymes called restriction enzymes to generate DNA building blocks that then can be “stitched” together in the correct order of the viral genome. To make a virus in the lab, researchers usually engineer the viral genome to add and remove stitching sites, called restriction sites. The ways researchers modify these sites can serve as fingerprints of in vitro genome assembly. We found that SARS-CoV has the restriction site fingerprint that is typical for synthetic viruses. The synthetic fingerprint of SARS-CoV-2 is anomalous in wild coronaviruses, and common in lab-assembled viruses. The type of mutations (synonymous or silent mutations) that differentiate the restriction sites in SARS-CoV-2 are characteristic of engineering, and the concentration of these silent mutations in the restriction sites is extremely unlikely to have arisen by random evolution. Both the restriction site fingerprint and the pattern of mutations generating them are extremely unlikely in wild coronaviruses and nearly universal in synthetic viruses. Our findings strongly suggest a synthetic origin of SARS-CoV2.

Competing Interest Statement ADW owns shares of a life insurance company and is a co-founder of Selva. 

Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv

 Posted October 20, 2022.

LEGAL POSITIVISM, CONSTITUTIONAL RIGHTS AND NATURAL IMMUNITY REGARDING SARS-COV-2

EL ESTUDIO DEL DR. STEVEN QUAY SOBRE EL ORIGEN DEL COVID 19