Luqman Ali Syed, Ali Awais, Ullah Waseef, Alamri Abdulaziz, Mohammed Khatrawi Elham, Sagimova Gulzira, Almabayeva Aigul, Rakhimzhanova Farida, Askarova Gulsum, Suleimenova Fatima, Al-Mahrami Nabras, Kumar Parida Prasanta
Department of Biochemistry, Abdul Wali Khan University Mardan (AWKUM), Mardan 23200, Paksitan.
Department of Biochemistry, Abdul Wali Khan University Mardan (AWKUM), Mardan 23200, Paksitan.
J Genet Eng Biotechnol. 2024 Dec;22(4):100439. doi: 10.1016/j.jgeb.2024.100439. Epub 2024 Nov 16.
The coronavirus that causes serious acute respiratory syndrome. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still a major problem in public health and biomedicine. Even if there is no cure for it, the infection is still progressing naturally, and the only time that optimal treatment choices, such as doxycycline, work is at the beginning of the infection. Our project is structured into two critical parts: the first focuses on the identification of potential drug targets, and the second on vaccine design, both aimed at exploring new ways to treat the disease. Initially, cytoplasmic proteins identified through subtractive analysis underwent comprehensive evaluation for potential drug targeting, focusing on metabolic pathways, homology prediction, drugability assessment, essentiality, and protein-protein interactions. Subsequently, surface proteins underwent rigorous assessment for allergenicity, antigenicity, physiochemical attributes, conserved regions, protein interactions, and identification of B and T cell epitopes. Molecular docking and immunological simulation analyses were then employed to develop and characterize a multi-epitope vaccine, integrating findings from the aforementioned evaluations. Findings from the study point to six proteins as potential critical therapeutic targets for SARS-CoV-2, each of which is involved in a distinct metabolic process. The reverse vaccinology analysis suggested that the following proteins could be used as vaccine candidates: sp|P05106, sp|O00187, sp|Q9NYK1, sp|P05556, sp|P09958, and sp|Q9HC29. Four multi-epitope vaccine named as SARS-COV-2-, C1, C2, C3, and C4 was designed by utilizing different adjuvants and eighteen B cell overlapped epitopes which were predicted from top ranked protiens. Based on immune simulation study, the vaccine exhibited adequate immune-reactivity and favorable encounters with toll-type receptors (TLR4, TLR8, HLA, etc ACE), Among them the SARS-COV-2-C2 showed best binding affinity of which all receptors. Findings from this study could be a game-changer in the quest to develop a vaccine and medication that effectively combat SARS-CoV-2. It is necessary to do additional experimental analyses, nevertheless.
导致严重急性呼吸综合征的冠状病毒。严重急性呼吸综合征冠状病毒2(SARS-CoV-2)仍是公共卫生和生物医学领域的一个主要问题。即便目前尚无治愈方法,但感染仍在自然发展,而像强力霉素这样的最佳治疗选择仅在感染初期有效。我们的项目分为两个关键部分:第一部分专注于潜在药物靶点的识别,第二部分专注于疫苗设计,二者均旨在探索治疗该疾病的新方法。最初,通过消减分析鉴定出的细胞质蛋白针对潜在药物靶向进行了全面评估,重点关注代谢途径、同源性预测、成药性评估、必需性以及蛋白质 - 蛋白质相互作用。随后,表面蛋白针对致敏性、抗原性、理化属性、保守区域、蛋白质相互作用以及B和T细胞表位的识别进行了严格评估。接着采用分子对接和免疫模拟分析来开发和表征一种多表位疫苗,整合上述评估的结果。该研究结果指出六种蛋白质是SARS-CoV-2潜在的关键治疗靶点,每种蛋白质都参与一个独特的代谢过程。反向疫苗学分析表明,以下蛋白质可用作候选疫苗:sp|P05106、sp|O00187、sp|Q9NYK1、sp|P05556、sp|P09958和sp|Q9HC29。利用不同佐剂和从排名靠前的蛋白质预测出的18个B细胞重叠表位,设计了四种名为SARS-COV-2-、C1、C2和C4的多表位疫苗。基于免疫模拟研究,该疫苗表现出足够的免疫反应性,并且与Toll样受体(TLR4、TLR8、HLA等ACE)有良好的相互作用,其中SARS-COV-2-C2与所有受体的结合亲和力最佳。尽管如此,仍有必要进行额外的实验分析,本研究结果可能会在开发有效对抗SARS-CoV-2的疫苗和药物的探索中带来变革。