Aljabali Alaa A A, El-Tanani Mohamed, Barh Debmalya, Tambuwala Murtaza M
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan.
College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, United Arab Emirates.
Prog Mol Biol Transl Sci. 2025;213:171-214. doi: 10.1016/bs.pmbts.2024.03.002. Epub 2024 Mar 19.
The ongoing global health challenges posed by the SARS-CoV-2, the virus responsible for the COVID-19 pandemic, necessitate a deep understanding of its intricate strategies to evade the innate immune system. This chapter aims to provide insights into the sophisticated mechanisms employed by SARS-CoV-2 in its interaction with pattern recognition receptors (PRRs), with particular emphasis on Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs). By skillfully circumventing these pivotal components, the virus manages to elude detection and impairs the initiation of crucial antiviral immune responses. A notable aspect of SARS-CoV-2's immune evasion tactics lies in its strategic manipulation of cytokine production. This orchestrated modulation disrupts the delicate balance of inflammation, potentially leading to severe complications, including the notorious cytokine storm. In this regard, key viral proteins, such as the spike protein and nucleocapsid protein, emerge as pivotal players in the immune evasion process, further highlighting their significance in the context of COVID-19 pathogenesis. Acquiring a comprehensive understanding of these intricate immune evasion mechanisms holds immense promise for the development of effective treatments against COVID-19. Moreover, it is imperative for vaccine development to consider these evasion strategies to maximize vaccine efficacy. Future therapeutic interventions may involve targeting alternative pathways or augmenting the antiviral immune responses, thereby mitigating the impact of immune evasion, and fostering successful outcomes. By unraveling the underlying mechanisms of innate immune evasion, we advance our comprehension of COVID-19 pathogenesis and pave the way for the development of innovative therapeutic strategies. This comprehensive understanding catalyzes progress, enabling researchers and clinicians to devise novel approaches that combat the challenges posed by SARS-CoV-2 and ultimately improve patient outcomes.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引发了持续的全球健康挑战,该病毒导致了新冠疫情,因此有必要深入了解其逃避固有免疫系统的复杂策略。本章旨在深入探讨SARS-CoV-2与模式识别受体(PRR)相互作用时所采用的复杂机制,尤其着重于Toll样受体(TLR)和视黄酸诱导基因I样受体(RLR)。通过巧妙地规避这些关键成分,该病毒得以逃避检测,并损害关键抗病毒免疫反应的启动。SARS-CoV-2免疫逃避策略的一个显著方面在于其对细胞因子产生的策略性操控。这种精心策划的调节扰乱了炎症的微妙平衡,可能导致包括臭名昭著的细胞因子风暴在内的严重并发症。在这方面,关键的病毒蛋白,如刺突蛋白和核衣壳蛋白,在免疫逃避过程中成为关键角色,进一步凸显了它们在新冠发病机制中的重要性。全面了解这些复杂的免疫逃避机制对于开发针对新冠的有效治疗方法具有巨大的前景。此外,疫苗开发必须考虑这些逃避策略以最大化疫苗效力。未来的治疗干预可能涉及靶向替代途径或增强抗病毒免疫反应,从而减轻免疫逃避的影响,并促进成功的结果。通过揭示固有免疫逃避的潜在机制,我们增进了对新冠发病机制的理解,并为创新治疗策略的开发铺平了道路。这种全面的理解推动了进步,使研究人员和临床医生能够设计出应对SARS-CoV-2带来的挑战并最终改善患者预后的新方法。