Anti-SARS-CoV-2 potential of Cissampelos pareira L. identified by connectivity map-based analysis and in vitro studies

Abstract

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. 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. 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. 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. 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. Amongst all the tested compounds, Magnoflorine and Salutaridine exhibited the most potent and consistent strong in silico binding profiles with SARS-CoV2 therapeutic targets.

Signatures of medications in meditation: A Connectivity map analysis of transcriptomes from an inner engineering retreat

“…We leveraged the demonstrated capabilities of the connectivity map, to discern the potential pharmacological connections during meditation (7). This was tested using RNAseqbased transcriptomes from a clinical study involving 106 participants in an advanced inner engineering meditation retreat program (5).…”

“…We hypothesized that the molecular targets underlying meditation’s response might overlap with those modulated by pharmacological interventions. We used connectivity map (CMap) to query intersections of meditation response with over 3 million gene expressions of 5,000 small compounds and 3,000 genetic perturbations across 9 cell lines(6)(7). Our study revealed convergence with over 438 pharmaceutical drugs, which were strongly connected to neuroactive ligand receptor signalling pathways.…”

Ayurgenomics-based frameworks in precision and integrative medicine: Translational opportunities

“…CMAP analysis of CIPA revealed that the molecules in this drug have matching signatures with protein synthesis inhibitors, many of which are antiviral, and this could work through ESR1 axis (Haider et al, 2021 ). These were validated in infection models of dengue in cell lines and also showed a repurposing possibility in SARS-CoV2 infection (Haider et al, 2022 ). Moreover, the complete formulation was more effective compared to single molecules in SARS-CoV2 inhibition.…”

“…These studies have been primarily conducted on healthy individuals of extreme and contrasting constitution types that are most easily discernible at the level of composite phenotypes, and who also have contrasting responses and vulnerability (Prasher et al, 2017 ). There have been novel discoveries, iterative developments and insights as well as opportunities for translation into integrative medicine settings (Ahmad et al, 2012 ; Juyal et al, 2012 , 2022 ; Gheware et al, 2021a , 2021b ; Haider et al, 2021 , 2022 ; Table 1 ).…”

Synthesis, Antiacetylcholinesterase Activity, and Molecular Dynamics Simulation of Aporphine–benzylpyridinium Conjugates

“…They are found as common compositions in numerous plant families, such as Annonaceae, Menispermaceae, Ranunculaceae, and Lauraceae . Various biological activities of aporphine alkaloids and their congeners, such as antitumor, antimicrobial, antiviral, antiplasmodial, , leishmanicidal, , antioxidant, and acetylcholinesterase (AChE) inhibitory activities, , have been reported.…”