Abstract

DETERMINATION OF THE RATE OF ANTISENSE-RNA (asRNA) DUPLEX FORMATION WITH CORONAVIRUS mRNA AND POTENTIAL ADMINISTRATION METHODS

Ronald Bartzatt*

Abstract

Antisense-RNA (asRNA) is complementary to its target, which is usually mRNA, and can inhibit the formation of viral origin protein, as well as expression of a specific gene. There are many advantages for the study and pursuit of as RNAs for drug development. This study presents a simulation of as RNA duplexing to mRNA, with the intention of determining the possibilities of the use of asRNA for medicinal application toward the treatment of coronavirus infection. The intracellular mechanism of coronavirus entry in cell, uncoating of the virion, followed by RNA activity leading to protein assimilation, and finally exocytosis of virus particles is presented to demonstrate the possibility of as RNA intervention. The initial 266-bases of mRNA for coronavirus NSP1 protein has been identified; and this study presents 19 single-strand complementary asRNA units each having 14 nucleotide bases. A kinetic model is presented, utilizing a total of 19 units of asRNA, each having 14 consecutive bases for complementary binding to the coronavirus mRNA. The 19 units of asRNA are non-repetitive and nonoverlapping in the duplex formation with the 266-bases of coronavirus mRNA for protein NSP1. Assuming random duplex formation of asRNA to mRNA, it is possible to predict the number of duplexes formed for each passage of the 19 asRNA units targeting the 266-base mRNA. The number of duplex formed are determined over a total of 20 passages of the 19 units of complementary asRNA, which target the 266 base mRNA. ANOVA analysis of the number of duplex formed for 20 passages of 19 asRNA units showed that the number of duplex formed varies widely (P=.006). Analysis and graphing showed that the best fit of asRNA duplex formation to coronavirus mRNA is second-order (13 runs, P=.92). Rate of duplex formation is determined to be k = 3.979 x 10-3 /(duplex formed•passage). In addition, previous studies have shown that asRNA can be very successful for treatment of pulmonary disease through various methods of administration.

Keywords: corona virus, COVID-19, SARS, antisense RNA.