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Cyclooxygenase 2 (COX-2), the key enzyme involved in prostaglandin (PGs) production, is known to take part in inflammatory and immune responses. Though COX-2 inhibitors are therapeutically effective anti-inflammatory drugs, they deficit anti-thrombotic activity thus leading to increased cardiovascular diseases. Therefore, COX-2 inhibitors with improved therapeutic efficacy and tolerance are still needed. In recent years, traditional medicine systems have paid attention to the essential oil of genus

Inflammation is caused by a cascade of events, one of which is the metabolism of arachidonic acid, that begins with oxidation by the enzyme 5-lipoxygenase. 5-Lipoxygenase (5-LOX) plays an important role in the inflammation process by synthesizing leukotrienes and several lipid mediators and has emerged as a possible therapeutic target for treatment of inflammatory diseases such as asthma and rheumatoid arthritis. Most of the existing 5-LOX inhibitors are synthetic and exhibit adverse side effects. In view of this, there is need to search for an alternate source of 5-LOX inhibitor with minimal side effects. The essential oil of several species of Curcuma has received considerable attention in recent times in traditional system of medicine especially for treating various inflammatory disorders. Therefore, the present study was carried out to screen the most potential 5-LOX inhibitors from essential oil components of Curcuma species and elucidate their mechanisms of action through computational biology approaches. Twenty-three phytoconstituents derived from the essential oil of Curcuma species were docked and their predictive binding energies were calculated to select the best possible ligand for 5-LOX. The top 8 ranked compounds from docking was tested for drug-likeness properties, bioactivity score, and toxicity analysis. The phytoconstituents such as α-turmerone, β-turmerone, α-terpineol and dihydrocarveolshowed the best binding affinity with 5-LOX and displayed favorable physicochemical properties. Molecular dynamics simulation in POPC lipid bilayers was carried out to understand the intrinsic dynamics and flexibility of the 5-LOX (apo) and 5-LOX-complex (α-terpineol, α-turmerone, β-turmerone and dihydrocarveol) systems. The molecular dynamic results showed that these 4 phytoconstituents interacted stably with the 5-LOX active site residues and the important bonds that were observed in the initial ligand docked compounds did not alter during the course of simulation. In general, our integrative computational approach demonstrated that the natural compounds like α-turmerone, β-turmerone, α-terpineol, and dihydrocarveol could be considered for designing specific anti-inflammatory drugs using structure-based drug design.

Furin, a pro-protein convertase, plays a significant role as a biological scissor in bacterial, viral, and even mammalian substrates which in turn decides the fate of many viral and bacterial infections along with the numerous ailments caused by cancer, diabetes, inflammations, and neurological disorders. In the wake of the current pandemic caused by the virus SARS COV-2, furin has become the center of attraction for researchers as the spike protein contains a polybasic furin cleavage site. In the present work, we have searched for novel inhibitors against this interesting human target from FDA-approved antivirals. To enhance the selection of new inhibitors we employed Kohonen’s artificial neural network-based self-organizing maps for ligand-based virtual screening. Promising results were obtained which can help in drug repurposing and network pharmacology studies addressing the errors generated due to promiscuity/polypharmacology. We found 15 existing FDA antivirals having the potential to inhibit furin. Among these, six compounds have targets on many important human proteins (LDLR, FCGR1A, PCK1, TLR7, DNA, and PNP) also. These 15 drugs inhibiting furin could be studied in patients infected with many viruses including SARS COV-2. We also propose two promising candidate FDA drugs GS-441524 and Grazoprevir (MK-5172) for repurposing as inhibitors of furin. The best results were observed with GS-441524.

Furin, a pro-protein convertase, plays a significant role of biological scissor in bacterial, viral, and even mammalian substrates which in turn decides the fate of many viral and bacterial infections along with the numerous ailments caused by cancer, diabetes, inflammations, and neurological disorders. In the wake of the current pandemic caused by the virus SARS COV-2, furin has become the center of attraction for researchers. In the present work, we have searched for novel inhibitors against this interesting human target from FDA-approved antivirals. To enhance the selection of new inhibitors we employed Kohonen’s-artificial neural network-based self-organizing maps for ligand based virtual screening. Promising results were obtained which can help in drug repurposing and network pharmacology studies addressing the errors due to promiscuity/polypharmacology. We found 15 existing FDA antivirals having the potential to inhibit furin. Among these, six compounds have targets on other important human proteins (LDLR, FCGR1A, PCK1, TLR7, DNA and PNP) also. These 15 drugs inhibiting furin could be studied in patients having many viral infections including SARS COV-2, which is known to have many interacting motifs like NSPs, ORFs, and spike protein. We also propose two promising candidate FDA drugs GS-441524 and Grazoprevir (MK-5172) to repurpose as inhibitors of furin. The best results were observed with GS-441524.

The emergence situation of coronavirus disease 2019 (COVID-19) pandemic has realised the global scientific communities to develop strategies for immediate priorities and long-term approaches for utilization of existing knowledge and resources which can be diverted to pandemic preparedness planning. Lack of proper vaccine candidate and therapeutic management has accelerated the researchers to repurpose the existing drugs with known preclinical and toxicity profiles, which can easily enter Phase 3 or 4 or can be used directly in clinical settings. We focused to justify even exploration of supplements, nutrients and vitamins to dampen the disease burden of the current pandemic may play a crucial role for its management. We have explored structure based virtual screening of 15 vitamins against non-structural (NSP3, NSP5, ORF7a, NSP12, ORF3a), structural (Spike & Hemagglutinin esterase) and host protein furin. The in silico analysis exhibited that vitamin B12, Vitamin B9, Vitamin D3 determined suitable binding while vitamin B15 manifested remarkable H-bond interactions with all targets. Vitamin B12 bestowed the lowest energies with human furin and SARS-COV-2 RNA dependent RNA polymerase. Furin mediated cleavage of the viral spike glycoprotein is directly related to enhanced virulence of SARS-CoV-2. In contrast to these, vitamin B12 showed zero affinity with SARS-CoV-2 spike protein. These upshots intimate that Vitamin B12 could be the wonder molecule to shrink the virulence by hindering the furin mediated entry of spike to host cell. These identified molecules may effectively assist in SARS-CoV-2 therapeutic management to boost the immunity by inhibiting the virus imparting relief in lung inflammation.

Toll-Like Receptors (TLRs) are a group of Pattern Recognition Receptors (PRRs) which bind to the exogenous pathogen associated molecular patterns (PAMPs) like other PRRs; hence the main function is to sense the harmness and mediate the innate immune response to pathogens. TLRs play an important role in innate immune responses to infection. The host has evolved to use other TLR and PAMP agonists as agents to stimulate a protective inflammatory immune response against infection. Because only a small number of doses are given, TLR agonists appear to have greater potential and fewer safety concerns than other uses as vaccine adjuvants. In the present days, development of peptides targeting immune response can be approved for survival in biological monitoring systems before vaccine exposures. Peptide vaccines are easy to synthesize, more stable and relatively safe. In addition, production of peptides becomes simple, easily reproducible, fast and cost effective. Getting vaccinated against Covid-19, which has become a pandemic in the human population, is the most practical way to control the outbreak. The new coronavirus does not contain a drug or vaccine to prevent it from spreading to humans. To getting a proper vaccine candidate against the novel coronavirus, the present study used the reverse vaccinology approach by using a complete set of SARS-CoV-2 proteins; such as: Spike, Envelope, Nucleocapsid, Membrane, NSPs, and ORFs to extract the antigenic elements that produce B-cell, T-cell and IFN positive epitopes. These epitopes with precise binding to the Toll-Like receptors (1-10) have developed epitope based vaccine candidates. We have prioritized a set of epitopes based on their antigenicity, allergenicity, sequence conservation and projected population coverage world-wide. The selected epitopes were employed for in-silico docking interactions with Toll-Like receptors and molecular dynamic simulation confirmed the stability of the vaccine candidates resulting epitope of spike proteins with both the TLR 7 and 8 shows the best binding affinity. We believe that this ideal epitope vaccine candidate could enhance the immune response of the host and reduce the reinfection risk.

The new severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is the etiological agent of Coronavirus disease 2019 (COVID-19), which becomes an eventual pandemic outbreak. Lack of proper therapeutic management has accelerated the researchers to repurpose existing drugs with known preclinical and toxicity profiles, which can easily enter Phase 3 or 4 or can be used directly in clinical settings. Vitamins are necessary nutrients for cell growth, function, and development. Furthermore, they play an important role in pathogen defence via cell-mediated responses and boost immunity. Using a computational approach, we intend to identify the probable inhibitory effect of all vitamins on the drug targets of COVID-19. The computational analysis demonstrated that vitamin B12 resulted in depicting suitable significant binding with furin, RNA dependent RNA polymerase (RdRp), Main proteases (Mpro), ORF3a and ORF7a and Vitamin D3 with spike protein and vitamin B9 with non structural protein 3 (NSP3). A detailed examination of vitamins suggests that vitamin B12 may be the component that reduces virulence by blocking furin which is responsible for entry of virus in the host cell. Details from the Molecular Dynamics (MD) simulation study aided in determining vitamin B12 as a possible furin inhibitor.