Comparative Genomic Analysis MERS CoV Isolated from Humans and Camels with Special Reference to Virus Encoded Helicase

Abstract

Middle East Respiratory Syndrome Coronavirus (MERS CoV)is a new emerging viral disease characterized by high fatality rate. Understanding MERS CoV genetic aspects and codon usage pattern is important to understand MERS CoV survival, adaptation, evolution, resistance to innate immunity, and help in finding the unique aspects of the virus for future drug discovery experiments. In this work, we provide comprehensive analysis of 238 MERS CoV full genomes comprised of human (hMERS) and camel (cMERS) isolates of the virus. MERS CoV genome shaping seems to be under compositional and mutational bias, as revealed by preference of A/T over G/C nucleotides, preferred codons, nucleotides at the third position of codons (NT3s), relative synonymous codon usage, hydropathicity (Gravy), and aromaticity (Aromo) indices. Effective number of codons (ENc) analysis reveals a general slight codon usage bias. Codon adaptation index reveals incomplete adaptation to host environment. MERS CoV showed high ability to resist the innate immune response by showing lower CpG frequencies. Neutrality evolution analysis revealed a more significant role of mutation pressure in cMERS over hMERS. Correspondence analysis revealed that MERS CoV genomes have three genetic clusters, which were distinct in their codon usage, host, and geographic distribution. Additionally, virtual screening and binding experiments were able to identify three new virus-encoded helicase binding compounds. These compounds can be used for further optimization of inhibitors.Key words codon usage; camel; Coronavirus; helicase; inhibitor Middle East Respiratory Syndrome Coronavirus (MERS CoV) is a new emerging virus infection causing lethal pneumonia and high case fatality.1-3) The infection with MERS CoV has now extended to become a global concern. 4-7)Recently, a serious outbreak of infection was recorded in South Korea and China. 8,9) MERS CoV is a single stranded RNA virus with a relatively large genome of ca. 30 kb.10) The virus was firstly isolated from humans. Currently there is still much debate in confirming the potential hosts and mode of transmission of the virus. Camels are incriminated as a potential host of the virus, and a considerable number of genomes of MERS CoV from camels were isolated and sequenced. [11][12][13] Therefore, there are two main sources of MERS CoV genomic data: humans and camels.The genetic code is comprised of 61 different codons corresponding to the standard 20 amino acids. Two of these amino acids are encoded by one codon (tyrosine (Tyr) and methionine (Met), while the other amino acids are encoded by several codons-up to 6 codons for 1 amino acid. Therefore, alternative codons present within 1 amino acid production codes are called synonymous codons.14) Codon bias infers the preference of one synonymous codon over the other, and may be over-represented to indicate overuse of a certain codon or rare codons that are rarely used for a certain gene. There are two main forces affecting the composition of a certain genome as well as codon usage...

A comprehensive analysis of genome composition and codon usage patterns of emerging coronaviruses

“…A mean ENC value of 48.54 ± 2.34 was obtained for SARS-CoV-2 strains enrolled in these studies, suggesting that the overall codon usage among SARS-CoV-2 is similar among themselves and slightly biased. This is in agreement with mean ENC values obtained for other CoV, like SARS-CoV (ENC = 48.99) (Gu et al, 2004); Bovine Coronavirus (BCoV) (ENC = 43.78) (Castells et al, 2017); MERS-CoV (ENC = 55.50) (Alnazawi et al, 2017) or Avian CoV (ENC = 51.33) (NSP2; Brandao, 2013). ENC-GC3s plot of the values obtained for SARS-CoV-2 revealed that all spots cluster below the expected curve, suggesting that G+C compositional constraints play a role in SARS-CoV-2 (see Fig.…”

From SARS and MERS CoVs to SARS‐CoV‐2: Moving toward more biased codon usage in viral structural and nonstructural genes

“…Codon usage bias is used in the analysis of genes composition and conclusion of the forces controlling evolution and functions 23,24 . It has been used in the analysis of viral structural 25,26 and nonstructural genes 25,27 . In this study, the codon usage bias and genomic composition were compared in structural proteins of the three major CoV epidemics—SARS, MERS, and SARS‐CoV‐2.…”

Using in silico modelling and FRET-based assays in the discovery of novel FDA-approved drugs as inhibitors of MERS-CoV helicase

“…Helicases are involved in molecular processes, including protein-nucleic acid complexes dissociation [16][17][18], Holliday junction displacement [19], chromatin remodelling [20], and conformational modifications of nucleic acid [21][22][23]. MERS-CoV is a positive single-stranded RNA (ssRNA) virus belonging to the Coronaviridae family, and has one of the largest known RNA genomes (~31.7 kb) [24,25]. The MERS-CoV genome is composed of ten open reading frames (ORFs).…”

“…The residue Tyr442 group contributes to the stabilization of the adenosine base [32]. Several S-nsp13 and M-nsp13 inhibitors have been identified using Förster resonance energy transfer (FRET)-based microplate screening assays [25,33,34]. Nsp13 inhibitors can either inhibit enzyme unwinding activity or inhibit its ATPase activity [35].…”