The broad-spectrum antiviral recommendations for drug discovery against COVID-19

Despite to outbreaks of highly pathogenic beta and alpha coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus, the newly emerged 2019 coronavirus (COVID-19) is considered as a lethal zoonotic virus due to its deadly respiratory syndrome and high mortality rate among the human. Globally, more than 3,517,345 cases have been confirmed with 243,401 deaths due to Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19. The antiviral drug discovery activity is required to control the persistence of COVID-19 circulation and the potential of the future emergence of coronavirus. However, the present review aims to highlight the important antiviral approaches, including interferons, ribavirin, mycophenolic acids, ritonavir, lopinavir, inhibitors, and monoclonal antibodies (mAbs) to provoke the nonstructural proteins and deactivate the structural and essential host elements of the virus to control and treat the infection of COVID-19 by inhibiting the viral entry, viral RNA replication and suppressing the viral protein expression. Moreover, the present review investigates the epidemiology, diagnosis, structure, and replication of COVID-19 for better understanding. It is recommended that these proteases, inhibitors, and antibodies could be a good therapeutic option in drug discovery to control the newly emerged coronavirus.HighlightsCOVID-19 has more than 79.5% identical sequence to SARS-CoV and a 96% identical sequence of the whole genome of bat coronaviruses.Acute respiratory distress syndrome (ARDS), renal failure, and septic shock are the possible clinical symptoms associated with COVID-19.Different antivirals, including interferons, ribavirin, lopinavir, and monoclonal antibodies (mAbs) could be the potent therapeutic agents against COVID-19.The initial clinical trials on hydroquinone in combination with azithromycin showed an admirable result in the reduction of COVID-19.The overexpression of inflammation response, cytokine dysregulation, and induction of apoptosis could be an well-organized factors to reduce the pathogenicity of COVID-19. COVID-19 has more than 79.5% identical sequence to SARS-CoV and a 96% identical sequence of the whole genome of bat coronaviruses. Acute respiratory distress syndrome (ARDS), renal failure, and septic shock are the possible clinical symptoms associated with COVID-19. Different antivirals, including interferons, ribavirin, lopinavir, and monoclonal antibodies (mAbs) could be the potent therapeutic agents against COVID-19. The initial clinical trials on hydroquinone in combination with azithromycin showed an admirable result in the reduction of COVID-19. The overexpression of inflammation response, cytokine dysregulation, and induction of apoptosis could be an well-organized factors to reduce the pathogenicity of COVID-19.

尽管此前已暴发高致病性β属和α属冠状病毒疫情，包括严重急性呼吸综合征冠状病毒（severe acute respiratory syndrome coronavirus, SARS-CoV）、中东呼吸综合征冠状病毒（Middle East respiratory syndrome coronavirus, MERS-CoV）以及人类冠状病毒，但新出现的2019冠状病毒（COVID-19）仍因其引发的致死性呼吸综合征和极高的人类病死率，被视为一种致命的人畜共患病毒。全球范围内，经确诊的COVID-19病例已超3517345例，其中243401例患者因该病引发的急性呼吸窘迫综合征（Acute Respiratory Distress Syndrome, ARDS）死亡。为遏制COVID-19的持续传播以及未来冠状病毒再度暴发的风险，亟需开展抗病毒药物研发工作。然而，本综述旨在阐述关键抗病毒策略：包括干扰素、利巴韦林、麦考酚酸、利托那韦、洛匹那韦、各类抑制剂以及单克隆抗体（monoclonal antibodies, mAbs），通过靶向病毒的非结构蛋白、使病毒结构蛋白与宿主必需元件失活，进而抑制病毒入侵、病毒RNA复制并阻断病毒蛋白表达，以此实现COVID-19感染的防控与治疗。此外，为增进学界对COVID-19的认知，本综述还探讨了其流行病学特征、诊断方法、病毒结构与复制机制。综上，此类蛋白酶、抑制剂与抗体有望成为防控新型冠状病毒感染的药物研发中的优质治疗候选方案。

研究亮点
1. COVID-19与SARS-CoV的序列同源性超过79.5%，与蝙蝠冠状病毒全基因组的同源性则达96%。
2. 急性呼吸窘迫综合征（ARDS）、肾衰竭与感染性休克均为COVID-19可能伴随的临床症状。
3. 干扰素、利巴韦林、洛匹那韦以及单克隆抗体（mAbs）等多种抗病毒药物均可作为对抗COVID-19的强效治疗制剂。
4. 氢醌联合阿奇霉素的早期临床试验显示，其在缓解COVID-19病情方面效果显著。
5. 炎症反应过度表达、细胞因子失调以及细胞凋亡诱导，或是降低COVID-19致病力的关键调控因素。

研究亮点
1. COVID-19与SARS-CoV的序列同源性超过79.5%，与蝙蝠冠状病毒全基因组的同源性则达96%。
2. 急性呼吸窘迫综合征（ARDS）、肾衰竭与感染性休克均为COVID-19可能伴随的临床症状。
3. 干扰素、利巴韦林、洛匹那韦以及单克隆抗体（mAbs）等多种抗病毒药物均可作为对抗COVID-19的强效治疗制剂。
4. 氢醌联合阿奇霉素的早期临床试验显示，其在缓解COVID-19病情方面效果显著。
5. 炎症反应过度表达、细胞因子失调以及细胞凋亡诱导，或是降低COVID-19致病力的关键调控因素。