Nature's therapy for COVID-19: Targeting the vital non-structural proteins (NSP) from SARS-CoV-2 with phytochemicals from Indian medicinal plants

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.

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Natures Therapy for COVID-19: Targeting the Vital Non-Structural Proteins (NSP) from SARS-CoV-2 with Phytochemicals from Indian Medicinal Plants

10.26434/chemrxiv.12661214.v2 ◽

2020 ◽

Author(s):

Pratap Kumar Parida ◽

Dipak Paul ◽

Debamitra Chakravorty

Keyword(s):

Medicinal Plants ◽

Health Sector ◽

Principal Component ◽

Binding Energies ◽

Structural Proteins ◽

P Value ◽

Pathway Enrichment Analysis ◽

Binding Modes ◽

Chemical Structures ◽

Indian Medicinal Plants

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.

Download Full-text