Neuroimmunology Section, Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th St., Hamilton, MT, USA.
Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th St., Hamilton, MT, USA.
Int J Antimicrob Agents. 2023 Sep;62(3):106893. doi: 10.1016/j.ijantimicag.2023.106893. Epub 2023 Jun 18.
Several coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human coronavirus OC43 (HCoV-OC43), can cause respiratory infections in humans. To address the need for reliable anti-coronavirus therapeutics, we screened 16 active phytochemicals selected from medicinal plants used in traditional applications for respiratory-related illnesses.
An initial screen was completed using HCoV-OC43 to identify compounds that inhibit virus-induced cytopathic effect (CPE) and cell death inhibition. Then the top hits were validated in vitro against both HCoV-OC43 and SARS-CoV-2 by determining virus titer in cell supernatant and virus-induced cell death. Finally, the most active phytochemical was validated in vivo in the SARS-CoV-2-infected B6.Cg-Tg(K18-ACE2)2Prlmn/J mouse model.
The phytochemicals lycorine (LYC), capsaicin, rottlerin (RTL), piperine and chebulinic acid (CHU) inhibited HCoV-OC43-induced cytopathic effect and reduced viral titres by up to 4 log. LYC, RTL and CHU also suppressed virus replication and cell death following SARS-CoV-2 infection. In vivo, RTL significantly reduced SARS-CoV-2-induced mortality by ∼40% in human angiotensin-converting enzyme 2 (ACE2)-expressing K18 mice.
Collectively, these studies indicate that RTL and other phytochemicals have therapeutic potential to reduce SARS-CoV-2 and HCoV-OC43 infections.
多种冠状病毒，包括严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）和人冠状病毒 OC43（HCoV-OC43），可引起人类呼吸道感染。为了满足对可靠抗冠状病毒疗法的需求，我们从用于治疗呼吸道相关疾病的传统应用草药中筛选了 16 种活性植物化学物质。
使用 HCoV-OC43 进行初步筛选，以鉴定抑制病毒诱导的细胞病变效应（CPE）和细胞死亡抑制的化合物。然后，通过测定细胞上清液中的病毒滴度和病毒诱导的细胞死亡，在体外对 HCoV-OC43 和 SARS-CoV-2 对排名靠前的化合物进行验证。最后，在 SARS-CoV-2 感染的 B6.Cg-Tg（K18-ACE2）2Prlmn/J 小鼠模型中对最活跃的植物化学物质进行体内验证。
植物化学物质石蒜碱（LYC）、辣椒素、罗氏菌素（RTL）、胡椒碱和诃子酸（CHU）抑制 HCoV-OC43 诱导的细胞病变效应，并将病毒滴度降低多达 4 个对数。LYC、RTL 和 CHU 还抑制了 SARS-CoV-2 感染后的病毒复制和细胞死亡。在体内，RTL 可使表达人血管紧张素转换酶 2（ACE2）的 K18 小鼠的 SARS-CoV-2 诱导死亡率降低约 40%。
综上所述，这些研究表明 RTL 和其他植物化学物质具有减少 SARS-CoV-2 和 HCoV-OC43 感染的治疗潜力。
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