Antiviral compound screening, peptide designing, and protein network construction of influenza a virus (strain a/Puerto Rico/8/1934 H1N1)

Abstract

Plant‐based antiviral therapy is the current need for holistic health care management, which can be achieved through screening of phytochemicals and designing of antiviral peptides. There exist certain host's factors which are directly involved for rapid viral replication causing worldwide pandemic. A total of 177 phytochemicals from Ocimum sanctum (L.), Tinospora cordifolia (Thunb.) Miers, Cinnamomum camphora (L.) J. Presl., Allium sativum (L.), Curcuma longa (L.), and Aloe vera (L.) Burm. f. were evaluated for their affinity to all viral proteins of H1N1. Applying drug filters and keeping the threshold of such filters relative to the standards, 82 compounds were found suitable for further analysis. Consensus scoring system was used for screening top ligands from 82 compounds, which screened the top 12 compounds. Highly conserved regions (>80%) which were hydrophilic, flexible, antigenic, and also charged were screened out as potent antiviral peptides. The viral proteins were taken as the targets for the modeled peptides for protein–protein docking. Further, host‐pathogen interacting network was constructed to unveil host factors involved in viral replication, from which unique protein clusters representing their involvement in viral reproduction were selected through mapping with pathway databases. Twelve compounds and five peptides were found to be highly effective against all the proteins of H1N1. Based on the uniqueness, 13 clusters of proteins were obtained which are engaged in cellular process, namely, viral reproduction, fructose‐6‐phosphate metabolism, nitrogen compound metabolism, biosynthesis, cellular process, oligodendrocyte development, localization, multiorganism process, primary metabolism, response to unfolded protein, metabolism, and response to protein and catabolism.

Efficacy of Natural Compounds from Tinospora cordifolia Against SARS-CoV-2 Protease, Surface Glycoprotein and RNA Polymerase

“…Also the currently available antiviral drugs (both approved and in clinical trials) are reported to have limited efficacy against SARS-CoV-2. 2,4,5 Hence there is an urgent need for identifying effective antiviral drugs against SARS-CoV-2. 6 Natural products have been viable and sustainable source of antimicrobial agents in the past and several natural compounds are reported to have antiviral properties.…”

“…6 Natural products have been viable and sustainable source of antimicrobial agents in the past and several natural compounds are reported to have antiviral properties. 5,[7][8][9] Recently we have shown the efficacy of neem and tulsi based natural compounds against the key SARS-CoV-2 targets. 10 Tinospora cordifolia (TC), a deciduous, extensively-spreading, climbing her baceous vine of the family Menispermaceae is considered an essential herbal plant in the Indian system of medicine.…”

Efficacy of natural compounds from Tinospora cordifolia against SARS-CoV-2 protease, surface glycoprotein and RNA polymerase.

“…The natural compounds from Tinospora cordifolia tested in this study showed therapeutically feasible efficacy against SARS-CoV-2 targets involved in attachment of the virus to host receptor (6VSB, 6M0J) and its replication (6M71, 6Y84). Although antiviral properties of Tinospora cordifolia has been reported before against H1N1 and Chikungunya Virus, [5,17,18] .27, 33.39±1.57, 66.79±3.14) against 6VSB was either similar or inferior to the natural compounds from Tinospora cordifolia. [6,10] 6VSB and 6M0J are responsible for viral attachment, while 6Y84 (main Protease) and 6M71 (RNA dependent RNA polymerase) are involved in viral replication.…”

“…[6] Natural products have been viable and sustainable source of antimicrobial agents in the past and several natural compounds are reported to have antiviral properties. [5,[7][8][9] Recently we have shown the efficacy of neem and tulsi based natural compounds against the key SARS-CoV-2 targets. [10] Tinospora cordifolia (TC), a deciduous, extensively-spreading, climbing herbaceous vine of the family Menispermaceae is considered an essential herbal plant in the Indian system of medicine.…”

“…[17] Phytochemicals from TC are also reported be effective inhibitors of H1N1 viral proteins. [5] TC is also a vital component of Shilajatu Rasayana (an Ayurvedic preparation), which was reported to synergistically improve efficacy of antiretroviral therapy in HIV positive patients. [18] Considering the positive reports of antiviral activity of Tinospora cordifolia, in this study the efficacy of some selected natural compounds reported in Tinospora cordifolia extracts were screened using Insilco pharmacology against three SARS-CoV-2 targets (Surface glycoproteins (6VSB, 6M0J); RNA dependent RNA polymerase (6M71) and Main Protease (6Y84)).…”