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.

Functions of MAP3Ks in antiviral immunity

“…Vemurafenib and PLX-4720 are inhibitors of the B-Raf mutation V600 [ 152 , 153 ]. Vemurafenib interacts with the nucleotide-binding domain of the cell surface protein BiP, thus limiting viral replication by neutralizing viral binding [ 154 ].…”

“…In contrast, in another study, vemurafenib caused a time-dependent increase in the expression of angiotensin-converting enzyme 2 (ACE2), which may contribute to SARS-CoV-2 infection [ 155 ]. PLX-4720 interacts with receptor-interacting serine/threonine-protein kinase 1 (RIPK1) during SARS-CoV-2 infection [ 153 ]. RIPK1 is activated by nsp12 and regulates the expression of ACE2 to promote viral transmission.…”

HuCoPIA: An Atlas of Human vs. SARS-CoV-2 Interactome and the Comparative Analysis with Other Coronaviridae Family Viruses

“…In our study, we found UBE3A to interact with 14 SARS-CoV-2 and 14 MERS proteins. DCAF7 has also been reported as a drug target for COVID 19 [ 56 ]. DCAF7 is also found to interact with 14 SARS-CoV-2 and MERS proteins.…”