The unavailability of vaccine and medicines raised serious issues during COVID-19 pandemic and peoples from different parts of world relied on traditional medicine for their immediate recovery from COVID-19 and it found effective also. The current research aims to target COVID-19 immunological human host receptors i.e. angiotensin-converting enzyme (ACE)-2, interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α) and protease-activated receptor (PAR)-1 using curcumin derivatives to prevent viral infection and control overproduction of early clinical responses of COVID-19. Targeting these host proteins will mitigate the infection and will filter out many complications caused by these proteins in COVID-19 patients. It is proven through computer-aided computational modeling approaches, total 30 compounds of curcumin and its derivatives were chosen. Drug-likeness parameters were calculated for curcumin and its derivatives and 20 curcumin analogs were selected for docking analysis. From docking analysis of 20 curcumin analogs against five chosen human host receptor targets reveals 11 curcumin analogs possess least binding affinity and best interaction at active sites subjected to absorption, distribution, metabolism, excretion (ADME) analysis. Density functional theory (DFT) analysis of five final shortlisted curcumin derivatives was done to show least binding affinity toward chosen host target protein. Molecular dynamics simulation (MDS) was performed to observe behavior and interaction of potential drug hydrazinocurcumin against target proteins ACE-2 and PAR-1. It was performed at 100 nanoseconds and showed satisfactory results. Finally, our investigation reveals that hydrazinocurcumin possesses immunomodulatory and anti-cytokine therapeutic potential against COVID-19 and it can act as COVID-19 warrior drug molecule and promising choice of drug for COVID-19 treatment, however, it needs further in vivo clinical evaluation to commercialize as COVID-19 drug. Communicated by Ramaswamy H. Sarma

Lupeol, a triterpene bioactive compound isolated from Indian traditional plant Crateva adansonii acted as promising and alternative anti-inflammatory agent to treatments of diseases related to inflammation. The inflammatory process in the body serves an important function in the control and repair of injury. However, it is self-perpetuating in number of disease conditions, which must be prevented and treated. Worldwide most prescribing NASID drug shows severe side effects. Whereas drug from natural origin shows dual inhibition of inflammatory and analgesic target protein with more efficacy and less side effects than NSAID drugs. Our study aims to isolate and screen the analgesic and anti-inflammatory potential of lupeol, a pentacyclic triterpenoid isolated from leaf extract of Crateva adansonii belongs to Capparaceae family commonly used Indian traditional medicine for treating inflammatory diseases. Methanol and chloroform leaf extracts (ME and CE) and lupeol fraction (LF) of plant Crateva adansonii is investigated through employing in vivo male Wistar albino rat model. Acute toxicity study of C. adansonii ME and CE leaf extracts reveals that no mortality and no behavioral changes in experimental animals up to 2 g/kg. So no lethal dose we consider two optimal doses 200 and 400 mg of plant leaf extracts for in vivo inflammatory and analgesic study. In vivo acute and chronic anti-inflammatory activity was carried out through carrageenan-induced rat paw edema and cotton pellet-induced granuloma models. LF (100 mg/kg, oral route) of Crateva adansonii evoked highest percentage of inflammation inhibition (50 and 33.96% respectively) in both in vivo acute and chronic inflammation model among all tested samples (ME and CE 200 mg and 400 mg/kg, oral route) including reference standard (10 mg/kg, oral route) indomethacin. Carrageenan-challenged experimental animals were screened for one inflammatory marker enzyme myeloperoxidase (MPO), inflammatory products such as Prostaglandrin E2 (PGE2), and eight different cytokines markers (TNFα, IL-6, IFN γ, IL-1α, IL-1β, MCP-1, Rantes, and MIP) associated with inflammation reveals that LF (100 mg/kg, oral route) of Crateva adansonii shows prominent anti-inflammatory activity than reference standard indomethacin (10 mg/kg, oral route) over all these biological tested parameters. In vivo analgesic assays such as hot plate assay and acetic acid-induced writhing assay revealed that LF (100 mg/kg, oral route) possesses significant analgesic activity (11.60 s and 69.05%) when compared with standard drug pentazocine(10 mg/kg, oral route). Finally, we made an in silico screening of lupeol against analgesic (nAChR) and anti-inflammatory (COX-2) target proteins reveals that lupeol possess highest binding affinity with nAChR and COX-2 target proteins (− 8.5 and − 9.0 Kcal/mol) over the reference standard pentazocine and indomethacin (− 7.0 and − 8.4 Kcal/mol) respectively. The present study result provides a pharmacological evidences for analgesic and anti-inflammatory potential of lupeol isolated from Indian traditional plant Crateva adansonii act as a multi-target agent with immense anti-inflammatory potential targeting key molecules of inflammation such as MPO, PGE2, and eight pro-inflammatory cytokine markers. Outcome of present study is to find promising anti-inflammatory bioactive agents from the cheapest Indian traditional medicinal plant sources useful for pharmaceutical industries.

Anti-inflammatory phytocompounds from Crateva adansonii DC leaf extracts were identified by GCMS analysis and its anti-inflammatory potential was evaluated by in silico molecular docking study against inflammatory molecular targets. Three different (Aqueous, Methanol and Petroleum ether) dried leaf extracts of Crateva adansonii were obtained from soxhlet extraction method. Preliminary phytoconstituents analysis of three different leaf extracts of C. adansonii confirmed the presence of various major classes of bioactive phytoconstituents such as polyphenols (tannins and flavonoids), steroids, alkaloid, coumarin, carbohydrate and terpenoids. Among three leaf extracts, methanolic leaf extract possess highest total phenolic content of 77 ± 1.65 µg gallic acid equivalent (GAE)/g of dry weight of leaf extract, subsequently methanolic leaf extract also shows maximal in vitro antioxidant activity (DPPH scavenging activity) of 71.22 ± 1.32% among three different leaf extracts. GC-MS analysis of petroleum ether leaf extract revealed the presence of nine phytocompounds representing 95.43% peak area percentage, among nine identified phytocompounds three phytocompounds of C. adansonii possess anti-inflammatory property namely phytol, 1-Hexyl-2-Nitrohexane and 2-Isopropyl-5-Methylcyclohexyl 3-(1-(4-Chlorophenyl)-3-Oxobutyl)-Coumarin-4-Yl Carbonate were chosen for in silico molecular docking study against four inflammatory receptor targets (COX-2, TNFα, IL-1β and IL-6) and they shows less binding energy with highest docking score ranging from -15.9500 to 5.0869. The present study substantially indicated and proven that anti-inflammatory potential of phytocompounds from C. adansonii leaf extracts which can be exploited for commercial designing of novel anti-inflammatory drug to treat various inflammatory disorders.