Sohrab Sayed S, El-Kafrawy Sherif A, Abbas Aymn T, Bajrai Leena H, Azhar Esam I
Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Curr Pharm Des. 2021;27(32):3490-3500. doi: 10.2174/1381612827999210111194101.
The unusual pneumonia outbreak that originated in the city of Wuhan, China in December 2019 was found to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19.
In this work, we have performed an in silico design and prediction of potential siRNAs based on genetic diversity and recombination patterns, targeting various genes of SARS-CoV-2 for antiviral therapeutics. We performed extensive sequence analysis to analyze the genetic diversity and phylogenetic relationships, and to identify the possible source of virus reservoirs and recombination patterns, and the evolution of the virus as well as we designed the siRNAs which can be used as antivirals against SARS-CoV-2.
The sequence analysis and phylogenetic relationships indicated high sequence identity and closed clusters with many types of coronavirus. In our analysis, the full-genome of SARS-CoV-2 showed the highest sequence (nucleotide) identity with SARS-bat-ZC45 (87.7%). The overall sequence identity ranged from 74.3% to 87.7% with selected SARS viruses. The recombination analysis indicated the bat SARS virus is a potential recombinant and serves as a major and minor parent. We have predicted 442 siRNAs and finally selected only 19 functional, and potential siRNAs.
The siRNAs were predicted and selected based on their greater potency and specificity. The predicted siRNAs need to be validated experimentally for their effective binding and antiviral activity.
2019年12月起源于中国武汉市的不明原因肺炎疫情被发现是由严重急性呼吸综合征冠状病毒2（SARS-CoV-2），即新冠病毒引起的。
在这项研究中，我们基于遗传多样性和重组模式，对潜在的小干扰RNA（siRNA）进行了计算机辅助设计和预测，靶向新冠病毒的各种基因用于抗病毒治疗。我们进行了广泛的序列分析，以分析遗传多样性和系统发育关系，确定病毒储存库的可能来源、重组模式以及病毒的进化，同时设计了可作为抗新冠病毒药物的siRNA。
序列分析和系统发育关系表明，新冠病毒与多种冠状病毒具有高度的序列同一性和紧密的聚类。在我们的分析中，新冠病毒的全基因组与蝙蝠SARS-CoV-ZC45的序列（核苷酸）同一性最高（87.7%）。与选定的SARS病毒的总体序列同一性范围为74.3%至87.7%。重组分析表明，蝙蝠SARS病毒是一种潜在的重组病毒，可作为主要和次要亲本。我们预测了442个siRNA，最终仅筛选出19个具有功能且有潜力的siRNA。
基于其更高的效力和特异性对siRNA进行了预测和筛选。预测的siRNA需要通过实验验证其有效结合和抗病毒活性。
