Genomics & molecular medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi, 110007, India.
Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, 201002, India.
BMC Complement Med Ther. 2022 Apr 22;22(1):114. doi: 10.1186/s12906-022-03584-3.
Viral infections have a history of abrupt and severe eruptions through the years in the form of pandemics. And yet, definitive therapies or preventive measures are not present. Herbal medicines have been a source of various antiviral compounds such as Oseltamivir, extracted using shikimic acid from star anise (Illicium verum) and Acyclovir from Carissa edulis are FDA (Food and Drug Administration) approved antiviral drugs. In this study, we dissect the anti-coronavirus infection activity of Cissampelos pareira L (Cipa) extract using an integrative approach.
We analysed the signature similarities between predicted antiviral agents and Cipa using the connectivity map ( https://clue.io/ ). Next, we tested the anti-SARS-COV-2 activity of Cipa in vitro. Molecular docking analyses of constituents of with key targets of SARS-CoV2 protein viz. spike protein, RNA‑dependent RNA‑polymerase (RdRp) and 3C‑like proteinase. was also performed. A three-way comparative analysis of Cipa transcriptome, COVID-19 BALF transcriptome and CMAP signatures of small compounds was also performed.
Several predicted antivirals showed a high positive connectivity score with Cipa such as apcidin, emetine, homoharringtonine etc. We also observed 98% inhibition of SARS-COV-2 replication in infected Vero cell cultures with the whole extract. Some of its prominent pure constituents e.g. pareirarine, cissamine, magnoflorine exhibited 40-80% inhibition. Comparison of genes between BALF and Cipa showed an enrichment of biological processes like transcription regulation and response to lipids, to be downregulated in Cipa while being upregulated in COVID-19. CMAP also showed that Triciribine, torin-1 and VU-0365114-2 had positive connectivity with BALF 1 and 2, and negative connectivity with Cipa. Amongst all the tested compounds, Magnoflorine and Salutaridine exhibited the most potent and consistent strong in silico binding profiles with SARS-CoV2 therapeutic targets.
病毒感染在过去的几年中一直以大流行的形式突然而严重地爆发。然而，目前还没有明确的治疗方法或预防措施。草药一直是各种抗病毒化合物的来源，如奥司他韦，它是从八角茴香（Illicium verum）中提取的莽草酸，阿昔洛韦是从 Carissa edulis 中提取的，已获得美国食品和药物管理局（FDA）批准的抗病毒药物。在这项研究中，我们采用综合方法剖析了 Cissampelos pareira L（Cipa）提取物的抗冠状病毒感染活性。
我们使用连接图谱（https://clue.io/）分析了预测的抗病毒药物与 Cipa 之间的特征相似性。接下来，我们在体外测试了 Cipa 对 SARS-COV-2 的活性。还对与 SARS-CoV2 蛋白的关键靶标（刺突蛋白、RNA 依赖性 RNA 聚合酶（RdRp）和 3C 样蛋白酶）的 Cipa 成分进行了分子对接分析。还对 Cipa 转录组、COVID-19 BALF 转录组和 CMAP 小分子特征进行了三向比较分析。
几种预测的抗病毒药物与 Cipa 具有很高的正连接得分，如 apcidin、 emetine、 homoharringtonine 等。我们还观察到整个提取物对感染的 Vero 细胞培养物中 SARS-COV-2 复制的抑制率达到 98%。其一些突出的纯成分，如 pareirarine、cissamine、magnoflorine 表现出 40-80%的抑制作用。BALF 和 Cipa 之间的基因比较显示，转录调节和对脂质的反应等生物学过程在 Cipa 中被下调，而在 COVID-19 中被上调。CMAP 还显示，Triciribine、torin-1 和 VU-0365114-2 与 BALF 1 和 2 具有正连接性，与 Cipa 具有负连接性。在所有测试的化合物中，Magnoflorine 和 Salutaridine 表现出与 SARS-CoV2 治疗靶点最有效和一致的强的计算机模拟结合特性。
