The stem loop 2 motif is a site of vulnerability for SARS-CoV-2

Abstract

SummaryThe SARS-CoV-2 virus contains an unusually large, single-stranded RNA genome that is punctuated with structured elements of unknown function, such as the s2m element located in the 3’ untranslated region. The evolutionary conservation of the s2m element and its occurrence in all viral subgenomic transcripts implicates a key role in the viral infection cycle. In order to exploit this element as a potential therapeutic target, we have designed antisense “gapmer” oligonucleotides that efficiently base-pair to the s2m region. These oligonucleotides, composed of locked nucleic acids (LNA) flanking a central DNA core, successfully remodel the s2m structure and induce sequence-specific RNA cleavage by RNase H in vitro. Gapmers are also effective in human cells as they reduce the fluorescence signal in GFP reporter assays and cause a dose-dependent reduction in replication in a model replicon system based on a human astrovirus. Overall, these oligonucleotides show promise as anti-viral agents and may serve as a helpful starting point to develop treatments for COVID-19.

Potential Achilles heels of SARS-CoV-2 are best displayed by the base order-dependent component of RNA folding energy

“…Thus, we have here repeated and expanded on past clarifications ( Forsdyke, 2007a , Xu et al, 2007 , Zhang et al, 2008b ) of the conceptual basis of a technology that has contributed to the understanding of many biological problems other than viral infections ( Forsdyke, 2016 ). Meanwhile, it is pleasing to note that, having identified a conserved interspecies element, others are addressing the targeting and therapy steps ( Lulla et al, 2021 ). Furthermore, with minimal evidence on targeting, much progress is being made with the therapy step ( Medeiros et al, 2021 , Haniff et al, 2020 , Chen et al, 2020 , Bush et al, 2021 , Hammond et al, 2021 ).…”

Aptamers for Detection and Diagnostics (ADD) is a proposed mobile app acquiring optical data from conjugated quantum nanodots to identify molecules indicating presence of SARS-CoV-2 virus: Why public health and healthcare need smartphone sensors as a platform for early detection and prevention

“…This mundane proposal is an elusive quest for an alternative path, albeit temporary and vastly incomplete, perhaps through the use of aptamers (or other variations based on oligonucleotides 241 ) to partially bridge the chasm of inequity 242 and cushion the blow from the mortality and morbidity, yet to be witnessed. Healthcare is a pillar (FEWSHE -food, energy, water, sanitation, healthcare, education) of life and living but it is prudent to avoid indulging in any illusion or delusion because neither aptamers nor vaccines or CRISPR tools, irrespective of their respective efficacies, are a panacea for the restoration of civilization, even if this pandemic subsides in a few years.…”

Потенциальная Возможность Антисмысловой Терапии COVID-19

“…Таким образом, учитывая предыдущий опыт терапии антисмысловыми олигонуклеотидами, можно предположить, что эта стратегия может быть применена в качестве антивирусного препарата путем связывания и расщепления РНК SARS-CoV-2. Учитывая, что SARS-CoV-2 является РНК-вирусом, который не интегрируется в геном хозяина, стратегия использования антисмысловых олигонуклеотидов, по мнению ряда авторов, может дать эффективные результаты [5,11].…”