Understanding the activating mechanism of the immune system against COVID-19 by Traditional Indian Medicine: Network pharmacology approach

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions are occurring rapidly; it is raising the alarm around the globe. Though vaccines are currently available, the evolution and mutations in the SARS-CoV-2 threaten available vaccines' significance. The drugs are still undergoing clinical trials, and certain medications are approved for "emergency use" or as an "off-label" drug during the pandemic. These drugs have been effective yet accommodating side effects, which also can be lethal. Complementary and alternative medicine is highly demanded since it embraces a holistic approach. Since ancient times, natural products have been used as drugs to treat various diseases in the medical field and are still widely practiced. Medicinal plants contain many active compounds that serve as the key to an effective drug design. The Kabasura kudineer and Nilavembu kudineer are the two most widely approved formulations to treat COVID-19. However, the mechanism of these formulations is not well known. The proposed study used a network pharmacology approach to understand the immune-boosting mechanism by the Kabasura kudineer, Nilavembu kudineer, and JACOM in treating COVID-19. The plants and phytochemical chemical compounds in the Kabasura kudineer, Nilavembu kudineer, and JACOM were obtained from the literature. The Swiss target prediction algorithm was used to predict the targets for these phytochemical compounds. The common genes for the COVID-19 infection and the drug targets were identified. The gene-gene interaction network was constructed to understand the interactions between these common genes and enrichment analyses to determine the biological process, molecular functions, cellular functions, pathways involved, etc. Finally, virtual screening and molecular docking studies were performed to identify the most potential targets and significant phytochemical compounds to treat the COVID-19. The present study identified potential targets as ACE, Cathepsin L, Cathepsin B, Cathepsin K, DPP4, EGFR, HDAC2, IL6, RIPK1, and VEGFA. Similarly, betulinic acid, 5″-(2⁗-Hydroxybenzyl) uvarinol, antofine, (S)-1'-methyloctyl caffeate, (Z)-3-phenyl-2-propenal, 7-oxo-10α-cucurbitadienol, and PLX-4720 collectively to be potential treatment agents for COVID-19.

Keywords: COVID-19; JACOM; Kabasura kudineer; Network pharmacology; Nilavembu kudineer; SARS-CoV-2; Traditional Indian Medicine.

Fig. 1

Venn diagram showing the number of COVID-19 receptors, Compound targets and the common genes between the COVID-19 receptors and compound targets.

Fig. 2

Enrichment analysis using FunRich shows the most significant biological process, cellular component, biological pathway, and molecular function of the identified targets as the input. (A) Biological process for common receptors, (B) Cellular component for common receptors, (C) Biological pathway for common receptors, and (D) Molecular function for common receptors.

Fig. 3

(A) Pathway shows the transcriptional regulation by the AP-2 (TFAP2) transcription factor family. (B) Pathway showing the potential therapeutics for SARS.

Fig. 3

(A) Pathway shows the transcriptional regulation by the AP-2 (TFAP2) transcription factor family. (B) Pathway showing the potential therapeutics for SARS.

Fig. 4

The gene-gene interaction between the identified targets common to the COVID-19 receptors and compound targets.

Fig. 5

Visualization of the best interacting phytochemical with the identified targets. (A) ACE receptor with betulinic acid, (B) Cathepsin L receptor with 5″-(2⁗-Hydroxybenzyl)uvarinol, (C) Cathepsin B & K receptor with 5″-(2⁗-Hydroxybenzyl)uvarinol, (D) DPPR receptor with (−)-antofine, (E) EGFR receptor with S)-1′-methyloctyl caffeate, (F) HDAC2 with (Z)-3-phenyl-2-propenal, (G) IL6 with 7-oxo-10α-cucurbitadienol, (H) RIPK1 with PLX-4720, and (I) VEGFA with 5″-(2⁗-Hydroxybenzyl)uvarinol.