Department of Biochemistry, Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), JSS Academy of Higher Education & Research (JSS AHER), Mysore, India.
AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, India.
Front Immunol. 2020 Sep 18;11:552925. doi: 10.3389/fimmu.2020.552925. eCollection 2020.
Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease - 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. The clinical manifestations of this disease are pneumonia, lung injury, inflammation, and severe acute respiratory syndrome (SARS). Currently, there is no vaccine or effective pharmacological agents available for the prevention/treatment of SARS-CoV2 infections. Moreover, development of a suitable vaccine is a challenging task due to antibody-dependent enhancement (ADE) and Th-2 immunopathology, which aggravates infection with SARS-CoV-2. Furthermore, the emerging SARS-CoV-2 strain exhibits several distinct genomic and structural patterns compared to other coronavirus strains, making the development of a suitable vaccine even more difficult. Therefore, the identification of novel small molecule inhibitors (NSMIs) that can interfere with viral entry or viral propagation is of special interest and is vital in managing already infected cases. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, the development of novel inhibitors of ACE2/TMPRSS2 is likely to be beneficial in combating SARS-CoV-2 infections. However, the usage of ACE-2 inhibitors to block the SARS-CoV-2 viral entry requires additional studies as there are conflicting findings and severe health complications reported for these inhibitors in patients. Hence, the current interest is shifted toward the development of NSMIs, which includes natural antiviral phytochemicals and Nrf-2 activators to manage a SARS-CoV-2 infection. It is imperative to investigate the efficacy of existing antiviral phytochemicals and Nrf-2 activators to mitigate the SARS-CoV-2-mediated oxidative stress. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起的冠状病毒病 19（COVID-19）病例数量正在以惊人的速度增加（截至 2020 年 6 月 11 日，有 740 万例阳性病例），导致高死亡率（截至 2020 年 6 月 11 日，有 417956 人死亡）和经济损失（全球经济在 2020 年收缩了 3.2%）。这种疾病的临床表现为肺炎、肺损伤、炎症和严重急性呼吸综合征（SARS）。目前，尚无预防/治疗 SARS-CoV2 感染的疫苗或有效药物。此外，由于抗体依赖性增强（ADE）和 Th-2 免疫病理学，SARS-CoV-2 的感染加重，因此开发合适的疫苗是一项具有挑战性的任务。此外，与其他冠状病毒株相比，新出现的 SARS-CoV-2 株表现出几种不同的基因组和结构模式，这使得开发合适的疫苗更加困难。因此，鉴定能够干扰病毒进入或病毒繁殖的新型小分子抑制剂（NSMIs）特别有趣，对于管理已感染的病例至关重要。SARS-CoV-2 感染是通过病毒 Spike 蛋白（S 蛋白）与人类细胞通过两步过程结合介导的，该过程涉及血管紧张素转换酶 2（ACE2）和跨膜丝氨酸蛋白酶（TMPRSS）-2。因此，开发新型 ACE2/TMPRSS2 抑制剂可能有助于对抗 SARS-CoV-2 感染。然而，使用 ACE-2 抑制剂来阻止 SARS-CoV-2 病毒进入需要进一步的研究，因为这些抑制剂在患者中存在相互矛盾的发现和严重的健康并发症。因此，目前的兴趣转移到开发 NSMIs，包括天然抗病毒植物化学物质和 Nrf-2 激活剂，以管理 SARS-CoV-2 感染。调查现有抗病毒植物化学物质和 Nrf-2 激活剂缓解 SARS-CoV-2 介导的氧化应激的功效至关重要。因此，在这篇综述中，我们回顾了 SARS-CoV-2 的结构特征，特别强调了关键的分子靶标及其已知的调节剂，这些调节剂可用于开发 NSMIs。
