Rahman Anisur, Gupta Shipan Das, Rahman Md Anisur, Tamanna Saheda
Department of Biotechnology and Genetic Engineering, Faculty of Science, Noakhali Science and Technology University, Noakhali 3814, Bangladesh.
Genomics Inform. 2021 Dec;19(4):e47. doi: 10.5808/gi.21057. Epub 2021 Dec 31.
Kaposi's sarcoma-associated herpesvirus (KSHV) is one of the few human oncogenic viruses, which causes a variety of malignancies, including Kaposi's sarcoma, multicentric Castleman disease, and primary effusion lymphoma, particularly in human immunodeficiency virus patients. The currently available treatment options cannot always prevent the invasion and dissemination of this virus. In recent times, siRNA-based therapeutics are gaining prominence over conventional medications as siRNA can be designed to target almost any gene of interest. The ORF57 is a crucial regulatory protein for lytic gene expression of KSHV. Disruption of this gene translation will inevitably inhibit the replication of the virus in the host cell. Therefore, the ORF57 of KSHV could be a potential target for designing siRNA-based therapeutics. Considering both sequence preferences and target site accessibility, several online tools (i-SCORE Designer, Sfold web server) had been utilized to predict the siRNA guide strand against the ORF57. Subsequently, off-target filtration (BLAST), conservancy test (fuzznuc), and thermodynamics analysis (RNAcofold, RNAalifold, and RNA Structure web server) were also performed to select the most suitable siRNA sequences. Finally, two siRNAs were identified that passed all of the filtration phases and fulfilled the thermodynamic criteria. We hope that the siRNAs predicted in this study would be helpful for the development of new effective therapeutics against KSHV.
卡波西肉瘤相关疱疹病毒（KSHV）是少数几种人类致癌病毒之一，它会引发多种恶性肿瘤，包括卡波西肉瘤、多中心性Castleman病和原发性渗出性淋巴瘤，尤其是在人类免疫缺陷病毒患者中。目前可用的治疗方案并不能总是预防这种病毒的侵袭和传播。近年来，基于小干扰RNA（siRNA）的疗法比传统药物更受关注，因为siRNA可以被设计用于靶向几乎任何感兴趣的基因。ORF57是KSHV裂解基因表达的关键调节蛋白。该基因翻译的破坏将不可避免地抑制病毒在宿主细胞中的复制。因此，KSHV的ORF57可能是设计基于siRNA疗法的潜在靶点。考虑到序列偏好和靶位点可及性，已使用几种在线工具（i-SCORE Designer、Sfold网络服务器）来预测针对ORF57的siRNA引导链。随后，还进行了脱靶筛选（BLAST）、保守性测试（fuzznuc）和热力学分析（RNAcofold、RNAalifold和RNA Structure网络服务器）以选择最合适的siRNA序列。最后，鉴定出两种通过所有筛选阶段并符合热力学标准的siRNA。我们希望本研究中预测的siRNA将有助于开发针对KSHV的新型有效疗法。
