UGC Sponsored Centre for Advanced Studies, Department of Chemistry, Guru Nanak Dev University, Amritsar, India.
Department of Chemistry, University of Petroleum & Energy Studies, Dehradun, India.
Drug Dev Res. 2021 Jun;82(4):469-473. doi: 10.1002/ddr.21794. Epub 2021 Jan 25.
Despite vigorous efforts, the COVID-19 pandemic continues to take a toll on the global health. The contemporary therapeutic regime focused on the viral spike proteins, viral 3CL protease enzyme, immunomodulation, inhibition of viral replication, and providing a symptomatic relief encouraged the repurposing of drugs to meet the urgency of treatment. Similarly, the representative drugs that proved beneficial to alleviate SARS-CoV-1, MERS-CoV, HIV, ZIKV, H1N1, and malarial infection in the past presented a sturdy candidature for ameliorating the COVID-19 therapeutic doctrine. However, most of the deliberations for developing effective pharmaceuticals proved inconsequential, thereby encouraging the identification of new pathways, and novel pharmaceuticals for capping the COVID-19 infection. The COVID-19 contagion encompasses a burst release of the cytokines that increase the severity of the infection mainly due to heightened immunopathogenicity. The pro-inflammatory metabolites, COX-2, cPLA2, and 5-LOX enzymes involved in their generation, and the substrates that instigate the origination of the innate inflammatory response therefore play an important role in intensifying and worsening of the tissue morbidity related to the coronavirus infection. The deployment of representative drugs for inhibiting these overexpressed immunogenic pathways in the tissues invaded by coronaviruses has been a matter of debate since the inception of the pandemic. The effectiveness of NSAIDs such as Aspirin, Indomethacin, Diclofenac, and Celecoxib in COVID-19 coagulopathy, discouraging the SARS viral replication, the inflammasome deactivation, and synergistic inhibition of H5N1 viral infection with representative antiviral drugs respectively, have provided a silver lining in adjuvant COVID-19 therapy. Since the anti-inflammatory NSAIDs and COXIBs mainly function by reversing the COX-2 overexpression to modulate the overproduction of pro-inflammatory cytokines and chemokines, these drugs present a robust treatment option for COVID-19 infection. This commentary succinctly highlights the various claims that support the status of immunomodulatory NSAIDs, and COXIBs in the adjuvant COVID-19 therapy.
尽管付出了巨大努力，但 COVID-19 大流行仍在继续对全球健康造成影响。当前的治疗方案侧重于病毒刺突蛋白、病毒 3CL 蛋白酶、免疫调节、抑制病毒复制以及提供对症缓解，这鼓励了药物的重新利用以满足治疗的紧迫性。同样，过去证明对缓解 SARS-CoV-1、MERS-CoV、HIV、ZIKV、H1N1 和疟疾感染有益的代表性药物为改善 COVID-19 治疗原则提供了强有力的候选药物。然而，大多数开发有效药物的讨论都没有结果，因此鼓励确定新的途径和新的药物来控制 COVID-19 感染。COVID-19 感染包括细胞因子的爆发释放，这些细胞因子会增加感染的严重程度，主要是由于免疫致病性增加。参与其产生的促炎代谢物、COX-2、cPLA2 和 5-LOX 酶以及引发固有炎症反应起源的底物在加剧和恶化与冠状病毒感染相关的组织发病机制方面发挥着重要作用。自大流行开始以来，代表抑制冠状病毒入侵组织中过度表达的免疫原性途径的药物的使用一直存在争议。非甾体抗炎药（如阿司匹林、吲哚美辛、双氯芬酸和塞来昔布）在 COVID-19 凝血功能障碍中的有效性、抑制 SARS 病毒复制、炎症小体失活以及与代表性抗病毒药物协同抑制 H5N1 病毒感染，为辅助 COVID-19 治疗提供了一线希望。由于抗炎性非甾体抗炎药和 COXIBs 主要通过逆转 COX-2 过表达来调节促炎细胞因子和趋化因子的过度产生来发挥作用，因此这些药物为 COVID-19 感染提供了强有力的治疗选择。本评论简明扼要地强调了支持免疫调节性 NSAIDs 和 COXIBs 在辅助 COVID-19 治疗中的各种说法。
