Abstract

Objective: The pandemic of coronavirus disease 2019 (COVID-19) is caused by infection with severe respiratory syndrome human coronavirus 2 (SARS-CoV-2). The spike (S) RNA of SARS-CoV-2 is used to build the COVID-19 vaccine. Although the level of immune response elicited by the full-length S RNA vaccine and the Receptor Binding Domain (RBD) vaccine that is a part of S is similar, the full-length S RNA vaccine is safer and lower reactogenicity than the RBD vaccine. However, the reason has not yet been clarified. On the other hand, the COVID-19 RNA vaccine with the S sequences may produce viral microRNAs (miRNAs). But there are no miRNA assessments for the safety of the COVID-19 vaccines. Therefore, evaluation as miRNA vaccines is necessary for risk management of vaccination.

Materials and Methods: miRNA Fold was used for pre-miRNA prediction in SARS-CoV-2 S RNA. MRmicro- T was used for protein target search. The integrated network algorithm as the miRNA entangling sorter (METS) analysis by using quantum miRNA language plus Artificial Intelligence (AI) were used as previously described.

Results: In computation, sixteen SARS-CoV-2-S-derived miRNAs bound to the negative strand S RNA with quite strong avidities. Further, CovS-miR-21 downregulated Rho associated coiled-coil containing protein kinase (ROCK2) and aryl hydrocarbon receptor nuclear translocator like (ARNTL), and CovSmiR- 3 decreased lysine methyltransferase 2C (KMT2C). Therefore, in the METS analysis, CovS-miR-21 suppressed the function of Ras homolog family member A (RhoA)/Rock2 signaling and circadian rhythm, and CovS-miR-3 inhibited histone H3-K4 methylation.

Conclusion: We found that BNT162b2 inhibits SARS-CoV-2 replication through degradation of negative strand viral RNAs that are completely paired with SARS-CoV-2 S-derived miRNAs. Further, CovS-miR-21 derived from BNT162b2 restores circadian rhythm and attenuate immunogenicity. Quantum miRNA assessments showed that the BNT162b2 RNA vaccine has a character of miRNA vaccine and is an excellent vaccine with high efficacy and low side-effects.

Keywords: COVID-19; SARS-CoV-2; BNT162b2; RNA vaccine; microRNA; Computer simulation; In silico; Circadian rhythm; Rho pathway