In March 2019, the World Health Organization (WHO) announced the global outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is the virus responsible for the coronavirus disease 2019 (COVID-19), to be a pandemic.
Social distancing or self-isolation alone cannot be the antidote to this pandemic. Even after the development of effective vaccines and the commencement of global vaccination campaigns, health officials continue to report a high percentage of people who are reluctant to be vaccinated. Further, the continuous emergence of SARS-CoV-2 variants has challenged the effectiveness of approved vaccines.
These factors, therefore, support the need to develop alternative approaches that could directly target SARS-CoV-2 particles. One potential approach that could be used to combat SARS-CoV-2 infection is to target the viral genome’s functional integrity using microRNAs (miRNAs).
Study: Identifying potential human and medicinal plant microRNAs against SARS-CoV-2 3′UTR region: A computational genomics assessment. Image Credit: ustas7777777 / Shutterstock.com
The SARS-CoV-2 genome
SARS-CoV-2 is a single-stranded positive-sense ribonucleic acid (RNA) virus belonging to the family Coronaviridae. This virus is approximately 26–32 kilobases (kb) in size and consists of 14 open reading frames (ORFs) that encode for 27 polyproteins.
SARS-CoV-2 encodes 16 non-structural proteins (nsps), accessory proteins, and structural proteins. The structural proteins of SARS-CoV-2 include the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. These proteins have been the primary targets for vaccine development, as well as drug repurposing and therapeutics studies.
The SARS-CoV-2 genome also consists of two flanking untranslated regions (UTRs) at the 5′ end of 265 nucleotides and 3′ end of 358 nucleotides. Typically, viruses take over the control of host cellular machinery, such as nucleic acid synthesis and protein translation system, in order to advance their replication within the host.
Researchers believe that if the functionality of the virus is silenced, the proteins that aid in the viral replication of the host cells will not be synthesized. Therefore, such gene silencing of the virus would lead to apoptosis of the infected cell.
Role of miRNA in combatting viral infection
miRNA is a non-immunogenic and single-stranded noncoding RNA that is about 22 nucleotides in size and is an important part of the eukaryotic cell.
The miRNAs that are endogenously found in humans are known as ‘cellular miRNAs,’ whereas those which are acquired by ingesting vegetables are known as ‘plant miRNAs.’ Taken together, these miRNAs play a vital role in regulating the expression of various genes at the post-transcriptional phase.
Several studies have shown that the main role of plant-derived miRNA is the repression or inhibition of gene expression. For example, a plant-derived miRNA known as ‘miRNA2911’ has been found to suppress the expression of the influenza A virus in mice.
miRNA and SARS-CoV-2 infection
In the context of inhibiting the SARS-CoV-2 gene, researchers found that the miRNA, present both endogenously inside the host or acquired exogenously through diet, could bind with the 3′ UTR flanking region of the virus via complementary binding. This interaction can repress protein translation or promote messenger RNA (mRNA) degradation to block protein translation.
A recent study has revealed that administering honeysuckle decoction, which consists of plant miRNA2911, could efficiently absorb and inhibit SARS-CoV-2 viral replication. This approach has shown that the miRNA of one species can interact and silence genes of another species, including viruses, via cross-kingdom interactions.
A new study published in the journal Computers in Biology and Medicine focuses on the identification of probable miRNA candidates from three medicinal plants; namely, Ocimum tenuiflorum, Zingiber officinale, and Piper nigrum, that are associated with cross-species interaction. Each of these plants is known to possess antiviral properties and can be consumed raw or as an herbal decoction.
To this end, the authors of this study have designed a systematic computational workflow to identify probable cellular miRNA candidates that are potent in providing antiviral defense against SARS-CoV-2 infection.
About the study
Herein, the researchers studied host-virus-plant interaction and have successfully identified one unique 3′UTR conserved site of ‘GGAAGAG’ among 5,024 globally submitted complete sequences of SARS-CoV-2. This conserved site can be targeted by both endogenous human miRNA (hsa-miR-1236–3p) and exogenous Z. officinale miRNA (zof-miR2673b).
Three miRNAs were identified and found to belong to the miR477 family. Typically, the members of the miR477 family have the inherent ability to silence viral genome RNA and promote antiviral activity. These results, therefore, highlight that the consumption of these three plants, either raw or in a decoction, could be effective in the prevention or management of COVID-19.
Conclusion
This study proposes that targeting the SARS-CoV-2’s 3′ UTR region with miRNA could trigger a silencing mechanism that can ultimately cause transcriptional repression. In this study, the researchers used the principle of cross-kingdom interaction, where plants were used as a potential source of exogenous miRNAs that could efficiently repress viral replication in the host
Herein, the authors identified one conserved 3′UTR site in SARS-CoV-2 genomes that can be targeted by human miRNA (hsa-miR-1236–3p) and Z. officinale miRNA (zof-miR2673b). Notably, a conserved site in the SARS-CoV-2 genome that could be effectively used as an alternative target to combat COVID-19 has also been identified.
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