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.

严重急性呼吸系统综合症-冠状病毒-2 (SARS-CoV-2) 诱发的冠状病毒病 - 19 (COVID-19) 病例以惊人的速度增加（截至 2020 年 6 月 11 日，阳性病例为 740 万例），造成高死亡率（截至 2020 年 6 月 11 日，全球 212 个国家/地区有 4,17,956 人死亡）和经济损失（2020 年全球经济萎缩 3.2%）。这种疾病的临床表现是肺炎、肺损伤、炎症和严重急性呼吸综合征（SARS）。目前，尚无疫苗或有效药物可用于预防/治疗 SARS-CoV2 感染。此外，由于抗体依赖性增强（ADE）和Th-2免疫病理学会加剧SARS-CoV-2的感染，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，新兴的 SARS-CoV-2 株表现出几种不同的基因组和结构模式，使得开发合适的疫苗变得更加困难。因此，鉴定能够干扰病毒进入或病毒传播的新型小分子抑制剂（NSMI）具有特别的意义，并且对于管理已经感染的病例至关重要。SARS-CoV-2 感染是由病毒刺突蛋白（S 蛋白）通过两步过程与人体细胞结合介导的，其中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 抑制剂可能有利于对抗 SARS-CoV-2 感染。然而，使用 ACE-2 抑制剂来阻止 SARS-CoV-2 病毒进入需要进行额外的研究，因为这些抑制剂在患者中的研究结果相互矛盾，并且报告了严重的健康并发症。因此，目前的兴趣转向 NSMI 的开发，其中包括天然抗病毒植物化学物质和 Nrf-2 激活剂来控制 SARS-CoV-2 感染。研究现有抗病毒植物化学物质和 Nrf-2 激活剂减轻 SARS-CoV-2 介导的氧化应激的功效势在必行。因此，在这篇综述中，我们回顾了 SARS-CoV-2 的结构特征，特别强调了可考虑用于 NSMI 开发的关键分子靶点及其已知调节剂。