Structural and Functional RNA Motifs of SARS-CoV-2 and Influenza A Virus as a Target of Viral Inhibitors

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic, whereas the influenza A virus (IAV) causes seasonal epidemics and occasional pandemics. Both viruses lead to widespread infection and death. SARS-CoV-2 and the influenza virus are RNA viruses. The SARS-CoV-2 genome is an approximately 30 kb, positive sense, 5' capped single-stranded RNA molecule. The influenza A virus genome possesses eight single-stranded negative-sense segments. The RNA secondary structure in the untranslated and coding regions is crucial in the viral replication cycle. The secondary structure within the RNA of SARS-CoV-2 and the influenza virus has been intensively studied. Because the whole of the SARS-CoV-2 and influenza virus replication cycles are dependent on RNA with no DNA intermediate, the RNA is a natural and promising target for the development of inhibitors. There are a lot of RNA-targeting strategies for regulating pathogenic RNA, such as small interfering RNA for RNA interference, antisense oligonucleotides, catalytic nucleic acids, and small molecules. In this review, we summarized the knowledge about the inhibition of SARS-CoV-2 and influenza A virus propagation by targeting their RNA secondary structure.

Keywords: COVID-19; RNA interference; RNA structure; SARS-CoV-2; antisense oligonucleotides; antiviral strategies; influenza A virus; small molecules.

Figure 1

Scheme of SARS-CoV-2 5′UTR. The positions of the uAUG and the AUG codons are highlighted in pink boxes. Black circles indicate TRS sequences. Blue and red letter colors mark paired and unpaired nucleotides, respectively.

Figure 2

Scheme of SARS-CoV-2 3′UTR. Blue and red letter colors mark paired and unpaired nucleotides, respectively.

Figure 3

Scheme of the selection strategy of targeting sites of SARS-CoV-2 and influenza A virus RNA and choice of inhibition tools.

Figure 4

Secondary structure of influenza A virus panhandle. Blue and red letter colors mark paired and unpaired nucleotides, respectively.

Figure 5

Pseudoknot (A) and hairpin (B) secondary structure of segment 8 (+) RNA of the IAV. Blue and red letter colors mark paired and unpaired nucleotides, respectively.

Figure 6

Secondary structure motifs of influenza A virus RNA that appeared to be a good target for inhibitors of virus propagation. (A)—M121 motif; (B)—selected motif of mRNA5; (C)—selected motif of vRNA8. Blue and red letter colors mark paired and unpaired nucleotides, respectively.