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Abstract
Containing COVID-19 is still a global challenge. It has affected the "normal" world by
targeting its economy and health sector. Research is more focused on finding a cure to this
disease and is less concerned about other life threatening diseases like cancer. Thus we need to
develop a medical solution at the earliest. In this context the present work aimed to understand
the efficacy of 22 rationally screened phytochemicals from Indian medicinal plants obtained
from our previous work, following drug-likeness properties, against 6 non-structural-proteins
(NSP) from SARS-CoV-2. 100 ns molecular dynamics simulations were performed and
relative binding free energies were computed by MM/PBSA. Further, principal component
analysis, dynamic cross correlation and hydrogen bond occupancy were analyzed to
characterize protein–ligand interactions. Biological pathway enrichment analysis was also
carried out to elucidate the therapeutic targets of the phytochemicals in comparison to SARS-
CoV-2. The potential binding modes and favourable molecular interaction profile of 9
phytochemicals, majorly from Withania sominifera with lowest free binding energies, against
the SARS-CoV-2 NSP targets were identified. It was understood that phytochemicals and
repurposed drugs with steroidal moieties in their chemical structures formed stable interactions
with the NSPs. Additionally, human target pathway analysis for SARS-CoV-2 and
phytochemicals showed that cytokine mediated pathway and phosphorylation pathways were
with the most significant p-value. To summarize this work, we suggest a global approach of
targeting multiple proteins of SARS-CoV-2 with phytochemicals as a natural alternative
therapy for COVID-19. We also suggest that these phytochemicals need to be tested
experimentally to confirm their efficacy.
targeting its economy and health sector. Research is more focused on finding a cure to this
disease and is less concerned about other life threatening diseases like cancer. Thus we need to
develop a medical solution at the earliest. In this context the present work aimed to understand
the efficacy of 22 rationally screened phytochemicals from Indian medicinal plants obtained
from our previous work, following drug-likeness properties, against 6 non-structural-proteins
(NSP) from SARS-CoV-2. 100 ns molecular dynamics simulations were performed and
relative binding free energies were computed by MM/PBSA. Further, principal component
analysis, dynamic cross correlation and hydrogen bond occupancy were analyzed to
characterize protein–ligand interactions. Biological pathway enrichment analysis was also
carried out to elucidate the therapeutic targets of the phytochemicals in comparison to SARS-
CoV-2. The potential binding modes and favourable molecular interaction profile of 9
phytochemicals, majorly from Withania sominifera with lowest free binding energies, against
the SARS-CoV-2 NSP targets were identified. It was understood that phytochemicals and
repurposed drugs with steroidal moieties in their chemical structures formed stable interactions
with the NSPs. Additionally, human target pathway analysis for SARS-CoV-2 and
phytochemicals showed that cytokine mediated pathway and phosphorylation pathways were
with the most significant p-value. To summarize this work, we suggest a global approach of
targeting multiple proteins of SARS-CoV-2 with phytochemicals as a natural alternative
therapy for COVID-19. We also suggest that these phytochemicals need to be tested
experimentally to confirm their efficacy.
Supplementary materials
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