PT - JOURNAL ARTICLE AU - Madiha Haider AU - Vivek Anand AU - Dhwani Dholakia AU - M. Ghalib Enayathullah AU - Yash Parekh AU - Sushma Ram AU - Surekha Kumari AU - Anmol AU - Kiran Kumar Bokara AU - Upendra Sharma AU - Bhavana Prasher AU - Mitali Mukerji TI - Anti-SARS-CoV-2 potential of <em>Cissampelos pareira</em> L. identified by Connectivity map-based analysis and in vitro studies AID - 10.1101/2021.06.11.448155 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.06.11.448155 4099 - http://biorxiv.org/content/early/2021/06/13/2021.06.11.448155.short 4100 - http://biorxiv.org/content/early/2021/06/13/2021.06.11.448155.full AB - Background 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.Purpose Herbal medicines have been a source of various antiviral compounds. An accelerated repurposing potential of antiviral herbs can provide usable drugs and identify druggable targets. In this study, we dissect the anti-coronavirus activity of Cissampelos pareira L (Cipa). using an integrative approach.Methods 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. A three-way comparative analysis of Cipa transcriptome, COVID-19 BALF transcriptome and CMAP signatures of small compounds was also performed.Results 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.Competing Interest StatementThe authors have declared no competing interest.CMAPConnectivity MapBALFBronchoalveolar Lavage fluidESR1Estrogen Receptor 1ACE2Angiotensin-converting enzyme 2SARSSevere Acute Respiratory SyndromeMERSMiddle East respiratory syndromeHDACHistone deacetylase