Jean claude Perez § Luc Montagnier - COVID-19, SARS and Bats Coronaviruses Genomes Unexpected Exogenous RNA Sequences

Abstract

We are facing the worldwide invasion of a new coronavirus. This follows several limited outbreaks of related viruses in various locations in a recent past (SARS, MERS). Although the main objective of researchers is to bring efficient therapeutic and preventive solutions to the global population, we need also to better understand the origin of the newly coronavirus-induced epidemic in order to avoid future outbreaks. The present molecular appraisal is to study by a bio-infomatic approach the facts relating to the virus and its precursors. This article shows how 16 fragments (Env Pol and Integrase genes) from different strains, both diversified and very recent, of the HIV1, HIV2 and SIV retroviruses most likely are present into the genome of COVID-19. Among these fragments, 12 are concentrated in a very small region of the COVID-19 genome, length less than 900bases, i.e. less than 3% of the total length of this genome. In addition, these footprints are positioned in 2 functional genes of COVID-19: the orf1ab and S spike genes. To sum up, here are the two main facts which contribute to our hypothesis of a partially synthetic genome: A contiguous region representing 2.49% of the whole COVID-19 genome of which 40.99% is made up of 12 diverse fragments originating from various strains of HIV SIV retroviruses. On the other hand, these 12 fragments some of which appear concatenated. Notably, the retroviral part of these regions, which consists of 8 elements from various strains HIV1, HIV2 and SIV covers a length of 275 contiguous bases of COVID-19. The cumulative length of these 8 HIV SIV elements represents 200 bases. Consequently, the HIV SIV density rate of this region of COVID-19 is 200/275 = 72.73%, which is considerable s made of. Moreover each of these elements is made of 18 or more nucleotides and therefore may have function. They are called Exogenous Informative Elements. A major part of these 16 EIE already existed in the first SARS genomes as early as 2003. However, we demonstrate how and why a new region including 4 HIV1 HIV2 Exogenous Informative Elements radically distinguishes all COVID-19 strains from all SARS and Bat strains. We then gather facts about the possible origins of COVID_19. We have particularly analyzed this small region of 225 bases common to COVID_19 and batRaTG13 but totally absent in all SARS strains. Then, we discuss the case of bat genomes presumed to be at the origin of COVID_19. In the strain of bat RaTG13 coronavirus isolated in 2013, then sequenced in 2020, the homology profile for HIV1 Kenya 2008 fragment is identical to that of COVID_19. Finally, we have studied the most recent genetic evolution of the COVID_19 strains involved in the world epidemic. We found a significant occurrence of mutations and deletions in the 225b region.On sampling genomes, we finally show that this 225b key region of each genome, rich in EIE, evolves much faster than the corresponding whole genome.The comparative analysis of the SPIKES genes of COVID_19 and Bat RaTG13demonstrates two abnormal facts: on the one hand, the insertion of 4 contiguous amino acids in the middle of SPIKE, on the other hand, an abnormal distribution of synonymous codons in the second half of SPIKE. Finally the insertion in this region of an EIE coming from a Plasmodium Yoelii gene is demonstrated, but above all seems to explain the "strategy" pursued by having "artificially" modified the ratio of synonym codons / non-synonymous codons in this same region of 1770 COVID_19 SPIKE nucleotides.