MicroRNA-29 family has high affinity to SARS-CoV-2 genome: an in silico analysis

MicroRNA-29 family has high affinity to SARS-CoV-2 genome: an in silico analysis
Saeideh Jafarinejad Farsangi,¹ Maryam Moazzam Jazi ,² Farzaneh Rostamzadeh,³ Morteza Hadizadeh,^4,*
1. Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
2. Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine sciences, Shahid Beheshti University of medical Sciences, Tehran, Iran
3. Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
4. Student Research Committee, School of Medicine, Kerman University of Medical Science, Kerman, Iran
Introduction: Coronavirus disease 2019 (COVID-19) caused by a novel betacoronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted top health concerns worldwide within a few months after appearance. COVID 19 as a single-stranded positive-sense RNA genome with the size of 26 – 32 kilobases (kb) in length, have the largest known genomes among all known RNA viruses. The virus genome possesses a 5′ cap structure together with a 3′ poly A tail, authorized act as mRNA molecules to translate its proteins. About two-thirds of the genome at 5´ end occupied by the replicase gene, which encoded two polyproteins, ORF1a and ORF1b. These polyproteins are further processed to generate the non-structural proteins (nsp). ORF1a is contributed to produce the nsp1-nsp11, while the rest of nsps (nsp12-nsp16) are originated from the ORF1b. Additionally, the viral structural proteins comprising surface (S), envelope (E), membrane (M), and nucleocapsid (N) proteins encoding by one third of genome at 3´ end. Viral proteins have been broadly considered as targets for antiviral therapies, but the problem arises when the selective pressure results to emergence of a new antiviral drug resistance lineage. Therefore, host coded factors and particularly, seem to be a better strategy MicroRNAs are a group of small non-coding RNAs, almost 19–24 base pairs in length. MiRNAs mediate their regulatory function through direct binding to the target transcript. Perfect pairing at the seed region (position 2 to 8 from 5’ end) has an important impact on the regulatory function of a miRNA. MiRNAs play a negative or positive role in viral-related processes in three ways: direct binding to the viral genome, binding to the viral transcripts, or binding to the host transcripts. Host miRNAs may promote viral RNA stability, replication, and infection or conversely, reinforced host antiviral responses against viruses. Since viruses are highly dependent on the host small RNAs (microRNAs) for their replication and propagation, we tried to predict top miRNAs involved in host-SARS-CoV-2 interface according to bioinfotmatics tools.
Methods: All human mature miRNA sequences acquired from miRBase database. MiRanda tool was used to predict the potential human miRNA binding sites on the SARS-CoV-2 genome. Additionally, the complete genome sequence of SARS-CoV-2 viruses isolated in the various geographical zones, including United states (MT322413.1), Spain (MT359865.1), France (MT470137.1), Japan (LC529905.1), South Africa (MT324062.1), India (MT415321.1), Brazil (MT350282.1), Australia (MT007544.1), Korea (MT304475.1) and Kazakhstan (MT428554.1) were obtained from NCBI database.
Results: Among the 2654 human mature miRNAs, 444 miRNAs were identified with direct binding site on different positions along the coronavirus 2 reference genome. We focused on the interactions with perfect matching at the seed region and sorted out 160 miRNAs. Among them, there was 15 miRNAs with more than three binging sites and 12 miRNAs bound to the coronavirus 2 reference genome with a free energy (ΔG) less than -29 kCal/Mol. MiR-29 family (miR-29a, miR-29b, miR-29c) had the most binding sites (11) on the SARS-CoV-2 genome. miR-29a, miR-29b and miR-29c had 5, 2 and 4 sites respectively. six sites on ORF1ab, three sites on nucleocapside and two sites on spike sequences of the SARS-CoV-2 genome. In particular, we explored the binding pattern of miR-29 family among genome sequences released from 10 different geographical locations and found no mutation and 100% similarity.
Conclusion: MiR-29a directly bind to the 3’UTR of the HIV genome, increased the virus’s transport to p-bodies and reduction of HIV replication. The inhibitory impact of miR-29a on HIV infection is mediated through binding to the accessory viral protein nef which is critical for viral persistence and release. Therefore, miR-29a has been considered as a potential therapy target for HIV eradication. Collectively, COVID-19 infection seems complicated and more experimental researches on the role of miR-29 family are needed to explore detailed molecular mechanisms of SARS-CoV-2 infection to clarify the similarities and differences between SARS-CoV-2 and other respiratory viruses.
Keywords: COVID-19; SARS-CoV-2; microRNA; microRNA-29 family