Author: Haider, Madiha; Dholakia, Dhwani; Panwar, Aleksha; Garg, Parth; Anand, Vivek; Gheware, Atish Prabhakar; Singhal, Khushboo; Singh, Dayanidhi; Burse, Shaunak A; Enayathullah, M Ghalib; Parekh, Yash; Ram, Sushma; Kumari, Surekha; Kumar, Anmol; Ray, Arjun; Medigeshi, Guruprasad R; Bokara, Kiran Kumar; Sharma, Upendra; Prasher, Bhavana; Mukerji, Mitali
Title: Traditional use of Cissampelos pareira L. for hormone disorder and fever provides molecular links of ESR1 modulation to viral inhibition Cord-id: ng6gq5ug Document date: 2021_1_1
ID: ng6gq5ug
Snippet: In traditional systems, a single herbal formulation is often used in the treatment of diverse diseases, including some that are newly emergent and prevalent today. We provide here a multi-omics framework to probe the molecular basis of a multicomponent example herb, Cissampelos pareira L. (Cipa) used in the treatment of hormonal disorders and fever in Ayurveda. Cipa treated MCF7 cells exhibit downregulation of signatures of estrogen response. 38 constituent molecules in Cipa potentially bind ({t
Document: In traditional systems, a single herbal formulation is often used in the treatment of diverse diseases, including some that are newly emergent and prevalent today. We provide here a multi-omics framework to probe the molecular basis of a multicomponent example herb, Cissampelos pareira L. (Cipa) used in the treatment of hormonal disorders and fever in Ayurveda. Cipa treated MCF7 cells exhibit downregulation of signatures of estrogen response. 38 constituent molecules in Cipa potentially bind ({triangleup}G< -7.5) with ER at the same site as estrogen. Cipa transcriptome signatures in the connectivity map exhibit positive scores with protein translation inhibitors and knockdown signatures of genes linked to the antiviral response. This includes the knockdown signature of RPL7, a coactivator of ESRI with a connectivity score > 99.92. This axis was found to be upregulated in the COVID-19 patient transcriptome. The antiviral activity through ESR1 modulation was validated in the DENV-2 infection model. We further observed 98% inhibition of SARs-COV-2 replication in infected Vero cell cultures with the whole extract. A few of its prominent pure constituents e.g pareirarine, cissamine, magnoflorine exhibited 40-80% inhibition. This study provides a novel framework for querying the molecular links of multicomponent Ayurveda formulations and explains their use in the treatment of disparate diseases. The novel biological targets identified here can become potential that could be applicable to more than one viral infection, such as the use of Cipa in dengue and COVID-19.
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