Discovery of potential microRNAs from humans and plants for SARS-CoV-2

In March 2019, the World Health Organization (WHO) announced that Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease (COVID-19) in 2019, is worldwide. Announced the outbreak. Pandemic.

Social distance and self-isolation alone cannot be an antidote to this pandemic. Even after the development of effective vaccines and the launch of global vaccination campaigns, health authorities continue to report a high percentage of people who are reluctant to vaccinate. In addition, the continued emergence of SARS-CoV-2 mutants has challenged the efficacy of approved vaccines.

Therefore, these factors support the need to develop alternative approaches that may directly target SARS-CoV-2 particles. One of the approaches that could be used to combat SARS-CoV-2 infection is to use microRNAs (miRNAs) to target the functional completeness of the viral genome.

study: Identification of potential human and medicinal plant microRNAs for the SARS-CoV-2 3’UTR region: Computational genomics assessment.. Image Credit: ustas7777777 / Shutterstock.com

SARS-CoV-2 genome

SARS-CoV-2 is a single-strand plus-strand ribonucleic acid (RNA) virus belonging to the family Coronaviridae. The virus is approximately 26-32 kilobases (kb) in size and consists of 14 open reading frames (ORFs) that encode 27 polyproteins.

SARS-CoV-2 encodes 16 nonstructural proteins (nsps), accessory proteins, and structural proteins. Structural proteins of SARS-CoV-2 include spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. These proteins are major targets for vaccine development, drug repositioning and therapeutic research.

The SARS-CoV-2 genome is also composed of two adjacent untranslated regions (UTRs) at the 5’end of 265 nucleotides and the 3’end of 358 nucleotides. Normally, the virus takes over control of the host’s cellular mechanisms, including: Nucleic acid A synthetic and protein translation system for promoting replication in a host.

Researchers believe that if the function of the virus is suppressed, proteins that aid in viral replication in the host cell are not synthesized. Therefore, such gene silencing of the virus will lead to apoptosis of infected cells.

The role of miRNAs in the fight against viral infections

miRNAs are non-immunogenic, single-stranded, non-coding RNAs, approximately 22 nucleotides in size, that are an important part of eukaryotic cells.

The miRNAs found endogenously in humans are known as “cellular miRNAs”, while the miRNAs obtained by ingesting vegetables are known as “plant miRNAs”. Taken together, these miRNAs play an important role in regulating the expression of various genes in the post-transcriptional stage.

Several studies have shown that the main role of plant-derived miRNAs is to suppress or inhibit gene expression. For example, a plant-derived miRNA known as “miRNA2911” has been shown to suppress the expression of influenza A virus in mice.

miRNA and SARS-CoV-2 infection

In the context of inhibiting the SARS-CoV-2 gene, researchers have found that miRNAs that are endogenously present in the host or acquired extrinsically through the diet are adjacent to the virus in the 3’UTR via complementary binding. I found that it can be combined with a region. This interaction can suppress protein translation or promote messenger RNA (mRNA) degradation to block protein translation.

Recent studies have shown that administration of a honeysuckle decoction consisting of plant miRNA2911 can efficiently absorb and inhibit SARS-CoV-2 virus replication. This approach shows that one type of miRNA can interact and silence another type of gene, including the virus, through cross-kingdom interactions.

New research published in the journal Biology and medicine computer It focuses on identifying potential miRNA candidates from three medicinal plants. in short, Ocimum tenuiflorum, Zingiber officinale, When Black pepper; Related to cross-species interactions.. Each of these plants is known to have antiviral properties and can be consumed raw or as an herbal decoction.

To this end, the authors of this study designed a systematic computational workflow to identify cellular miRNA candidates that may be potent in providing antiviral protection against SARS-CoV-2 infection. did.

About research

Here, researchers study host-virus-plant interactions and one unique 3’UTR preservation site of “GGAAGAG” from the 5,024 globally submitted complete sequences of SARS-CoV-2. Succeeded in identifying.This preserved site is a target for both endogenous human miRNA (hsa-miR-1236–3p) and exogenous Z. Officinal miRNA (zof-miR2673b).

Three miRNAs have been identified and found to belong to the miR477 family. Members of the miR477 family typically have the unique ability to silence viral genomic RNA and promote antiviral activity. Therefore, these results emphasize that ingestion of raw or decoctions of these three plants may be effective in the prevention or management of COVID-19.

Conclusion

This study suggests that targeting the 3’UTR region of SARS-CoV-2 with miRNAs may ultimately trigger silencing mechanisms that can lead to transcriptional repression. In this study, researchers used the principle of inter-kingdom interaction, where plants were used as a potential source of exogenous miRNAs that could effectively suppress viral replication in the host.

Here, the authors found human miRNA (hsa-miR-1236–3p) and Z. Officinal miRNA (zof-miR2673b). In particular, sites where the SARS-CoV-2 genome has been conserved have been identified that can be effectively used as alternative targets to combat COVID-19.