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

被引:21
作者
Alnazawi, Mohamed [1 ]
Altaher, Abdallah [1 ]
Kandeel, Mahmoud [1 ,2 ]
机构
[1] King Faisal Univ, Dept Physiol Biochem & Pharmacol, Fac Vet Med, Alahsa 31982, Saudi Arabia
[2] Kafrelshikh Univ, Dept Pharmacol, Fac Vet Med, Kafrelshikh 33516, Egypt
关键词
codon usage; camel; Coronavirus; helicase; inhibitor; CODON USAGE BIAS; SYNDROME CORONAVIRUS; DROMEDARY CAMELS; SOUTH-KOREA; OUTBREAK; PATTERNS; CPG;
D O I
10.1248/bpb.b17-00241
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:1289 / 1298
页数:10
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