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Source: COVID-19 Research  May 29, 2020  3 years, 10 months, 2 weeks, 6 days, 27 minutes ago

COVID-19 Research: University Of Massachusetts Study Warns Of Emerging Genomic Variants In SARS-CoV-2 Coronavirus That Could Lead To Drug Resistance

COVID-19 Research: University Of Massachusetts Study Warns Of Emerging Genomic Variants In SARS-CoV-2 Coronavirus That Could Lead To Drug Resistance
Source: COVID-19 Research  May 29, 2020  3 years, 10 months, 2 weeks, 6 days, 27 minutes ago
COVID-19 Research: A new research by University Of Massachusetts Medical School lead by Dr Sean P Ryder, a Professor Biochemistry and Molecular Pharmacology has demonstrated that there are numerous emerging genomic variants of the SARS-CoV-2 coronavirus and that some of these with changes on certain of parts of the structure of the genome, he warns could lead to drug resistance.


 
Dr Ryder told Thailand Medical News, “Structures with rapidly emerging variations are problematic for drug development as well, as the relatively high viral mutation rate, coupled to its potential to be edited by APOBEC and ADAR enzymes, and could lead to the rapid evolution of resistant variants.”
 
The study was just published a few hours ago on a preprint server and has yet to be peer reviewed but already a number of virologist and genomic experts are corroborating on the findings. https://www.biorxiv.org/content/10.1101/2020.05.27.120105v1.full.pdf+html
 
The research team evaluated two cohorts of SARS-CoV-2 genomic sequences to identify rapidly emerging variants within structured cis-regulatory elements of the SARS-CoV-2 genome.
 
On the whole, twenty variants are present at a minor allele frequency of at least 0.5%. Several enhance the stability of Stem Loop 1 in the 5´UTR, including a set of co-occurring variants that extend its length. One appears to modulate the stability of the frameshifting pseudoknot between ORF1a and ORF1b, and another perturbs a bi-stable molecular switch in the 3´UTR.
 
Finally, five variants destabilize structured elements within the 3´UTR hypervariable region, including the S2M stem loop, raising questions as to the functional relevance of these structures in viral replication. Two of the most abundant variants appear to be caused by RNA editing, suggesting host-viral defense contributes to SARS-CoV-2 genome heterogeneity.
 
This analysis has implications for the development therapeutics that target viral cis-regulatory RNA structures or sequences, as rapidly emerging variations in these regions could lead to drug resistance.
 
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The researchers used available data to investigate how rapidly emerging variants could impact structured cis-regulatory elements in the virus genome. These elements govern viral replication, su