Department of Pharmaceutical Sciences, Drug Discovery Research Laboratory, Assam University, Silchar, Assam-788011 India.
ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi, 590010, India; ICMR-National Institute of Cholera and Enteric Diseases, Kolkata 700010, India.
Phytomedicine. 2021 May;85:153396. doi: 10.1016/j.phymed.2020.153396. Epub 2020 Oct 28.
Currently, novel coronavirus disease (Covid-19) outbreak creates global panic across the continents, as people from almost all countries and territories have been affected by this highly contagious viral disease. The scenario is deteriorating due to lack of proper & specific target-oriented pharmacologically safe prophylactic agents or drugs, and or any effective vaccine. drug development is urgently required to back in the normalcy in the community and to combat this pandemic.
Thus, we have proposed two novel drug targets, Furin and TMPRSS2, as Covid-19 treatment strategy. We have highlighted this target-oriented novel drug delivery strategy, based on their pathophysiological implication on SARS-CoV-2 infection, as evident from earlier SARS-CoV-1, MERS, and influenza virus infection via host cell entry, priming, fusion, and endocytosis. STUDY DESIGN & METHODS: An earlier study suggested that Furin and TMPRSS2 knockout mice had reduced level of viral load and a lower degree of organ damage such as the lung. The present study thus highlights the promise of some selected novel and potential anti-viral Phytopharmaceutical that bind to Furin and TMPRSS2 as target.
Few of them had shown promising anti-viral response in both preclinical and clinical study with acceptable therapeutic safety-index.
Hence, this strategy may limit life-threatening Covid-19 infection and its mortality rate through nano-suspension based intra-nasal or oral nebulizer spray, to treat mild to moderate SARS-COV-2 infection when Furin and TMPRSS2 receptor may initiate to express and activate for processing the virus to cause cellular infection by replication within the host cell and blocking of host-viral interaction.
目前,新型冠状病毒病(Covid-19)的爆发在各大洲引起了全球恐慌,因为几乎所有国家和地区的人们都受到了这种高度传染性病毒疾病的影响。由于缺乏适当和特定的、有针对性的、药理安全的预防性药物或药物,以及有效的疫苗,情况正在恶化。迫切需要药物开发,以使社区恢复正常,应对这一大流行病。
因此,我们提出了两个新的药物靶点,弗林蛋白酶和 TMPRSS2,作为 Covid-19 的治疗策略。我们强调了这种基于靶点的新型药物输送策略,因为它们对 SARS-CoV-2 感染的病理生理学意义,这在早期 SARS-CoV-1、MERS 和流感病毒通过宿主细胞进入、启动、融合和内吞感染中得到了证明。
早期的一项研究表明,弗林蛋白酶和 TMPRSS2 敲除小鼠的病毒载量水平降低,肺部等器官的损伤程度降低。本研究因此强调了一些选定的新型和潜在的抗病毒植物药的前景,这些药物可以与弗林蛋白酶和 TMPRSS2 结合作为靶点。
其中一些药物在临床前和临床试验中表现出了有希望的抗病毒反应,且具有可接受的治疗安全性指数。
因此,这种策略可能通过基于纳米悬浮液的鼻内或口服雾化器喷雾来限制危及生命的 Covid-19 感染及其死亡率,用于治疗轻度至中度 SARS-COV-2 感染,此时弗林蛋白酶和 TMPRSS2 受体可能开始表达并激活,以处理病毒,导致宿主细胞内复制引起细胞感染,并阻断宿主-病毒相互作用。