Alnazawi Mohamed, Altaher Abdallah, Kandeel Mahmoud
Department of Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, King Faisal University.
Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelshikh University.
Biol Pharm Bull. 2017;40(8):1289-1298. doi: 10.1248/bpb.b17-00241.
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.
中东呼吸综合征冠状病毒(MERS-CoV)是一种新出现的病毒性疾病,其特征是致死率高。了解MERS-CoV的遗传特征和密码子使用模式对于理解MERS-CoV的生存、适应、进化、对先天免疫的抗性以及有助于发现该病毒的独特方面以用于未来的药物发现实验非常重要。在这项工作中,我们对由人类(hMERS)和骆驼(cMERS)分离株组成的238个MERS-CoV全基因组进行了全面分析。MERS-CoV基因组的形成似乎受到组成和突变偏差的影响,这通过A/T相对于G/C核苷酸的偏好、偏好密码子、密码子第三位的核苷酸(NT3s)、相对同义密码子使用、亲水性(Gravy)和芳香性(Aromo)指数得以揭示。有效密码子数(ENc)分析揭示了一般轻微的密码子使用偏差。密码子适应指数揭示了对宿主环境的不完全适应。MERS-CoV通过显示较低的CpG频率表现出对先天免疫反应的高抗性。中性进化分析表明,突变压力在cMERS中比在hMERS中发挥更重要的作用。对应分析表明,MERS-CoV基因组有三个遗传簇,它们在密码子使用、宿主和地理分布方面各不相同。此外,虚拟筛选和结合实验能够鉴定出三种新的病毒编码解旋酶结合化合物。这些化合物可用于进一步优化抑制剂。