Insilico

Novel Corona virus is making its Worldwide propagation in a very fast phase. It is now essential to discover the drugs that are useful in the prevention and management of NCoV-19. Many traditional Herbs and Poly Herbal synergistic formulations are useful in the prophylaxis of various types of Viruses. In Siddha system of medicine, there are various medicines used for antiviral therapies. Nilavembu kudineer is a very remarkable medicine which is already recognized by the Government of Tamilnadu during the eradication program of Dengue and Chikungunya viruses. To prove safety and efficacy of a traditional medicine, Reverse pharmacology method is recognized globally. Reverse pharmacology is confirming the safety and efficacy of a medicine which is already in clinical practice by going back in the steps of pharmacological screening and drug development. The ultimate aim of the Reverse pharmacological research is to find the mechanism of action by a drug against a disease. For Nilavembu kudineer (Mentioned in the Siddha text Siddha Vaithiya Thirattu), clinical documentations and various pre-clinical studies on its safety and efficacy are already done. In this study, we have done the In-silico Molecular Docking Analysis of the Bio-active compounds found in the aqueous extract of Nilavembu kudineer chooranam against the ACE2 enzyme receptor which is the route of entry in the pathogenesis of Novel corona virus. Clinical study needs to be done to confirm the proposed efficacy of the Nilavembu kudineer in the prevention of the Novel Corona Virus.

The Bcr-Abloncoprotein with constitutive tyrosine kinase activity plays a pivotal role in the pathogenesis of chronic
myeloid leukemia (CML), therefore being an ideal target for the drug development. Imatinibmesylate, a selective
tyrosine kinases inhibitor (TKI), has excellent efficacy in the treatment of chronic myeloid leukemia. It has opened the
way to the development of additional TKIs against chronic myeloid leukemia, including nilotinib and dasatinib. In this
study, computational methods are used to design novel imatinib derivatives and evaluated them for interaction with the
Bcr-Abloncoprotein through insilico analysis by using Hyperchem 8.0, Gold 3.01 docking software. Here, from the
results, it is reported that 1, 14, 26, ligands are having dock score near to imatinib and modifications to these ligands
may result in better ligands than imatinib. The results of Toxicity studies also supported 1, 14, 26, better drug-likeness
properties. Ligand 4 has shown higher affinity and better interaction with Bcr-Abloncoprotein than imatinib and any
other newly designed molecules, but it had shown mutagenicity and irritancy.

The best approach for the development of a vaccine against a specific infection or a microbial disease is Insilico vaccine designing that is not only accurate but also requires minimum time, labour and economy. This approach can also be used to analyze the target structures for possible binding/active sites, generate candidate molecules, check for their drug likeness, dock these molecules with the target, rank them according to their binding affinities, further optimize the molecules to improve binding characteristics. During vaccine designing the disease to be selected should be a viral or a bacterial disease but not due to a protozoan, as they cannot be attenuated and injected. The main goal of the current work is to develop a vaccine against the disease Ebola. Computational tools offer the advantage of delivering new drug candidates more quickly and at a lower cost. This review provides succinct overview of several methods in drug discovery by using insilico approaches on identifying drug targets where there are genes or proteins associated with specific diseases.

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a nuclear receptor family transcription factor that is expressed in several types of cancers. Antiproliferative and proapoptotic actions of PPARγ agonists suggesting that, it could be a promising therapeutic target for the treatment of variety of cancers. Therefore, the main aim of this study is attempt to identify the novel PPARγ agonist from presence of bioactive compounds in ethanolic extract of Cayratia trifolia using GC-MS analysis and Computational molecular simulation studies. The GC-MS analysis revealed that the ethanolic extract of Cayratia trifolia (L.) (whole plant) consist of 20 bioactive compounds which embrace many biological activities against variety of diseases. Molecular docking studies (Glide 5.5 from Schrödinger suite) exposed that, out of 20 bioactive compounds, Cyclopentadecane, 9- Borabicyclo [3.3.1]nonane, 9-(2-propen-1-yloxy)-.1, 4,8,12,16-Tetramethylheptadecan-4- olide, Oxirane and Vitamin E shows ...

Dengue fever also known as breakbone fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases, the disease develops into the life-threatening dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs. Dengue is transmitted by several species of mosquito within the genus Aedes, principally A. aegypti.

Lyme disease is an infectious disease caused by a spirochete Borrelia burgdorferi ZS7. This spirochete is most often spread by ticks. Single antibiotic therapy is sufficient for containment of the early stage progression of the disease but combinational therapy is more preferred in later stages. Research is in progress for the development of drugs against the pathogen, but till date no vaccines have been developed to effect the late stage infections. There is a rapid rise in the cases of antibiotic-resistant population which is more than 10% of the total infected individuals. In such condition vaccine becomes the sole alternative for prevention. Therefore effective treatment includes antibiotic combination and combination of antigenic surfaces (for vaccine preparation). Thus, a comprehensive list of drug targets unique to the microorganisms is often necessary. Availability of Borrelia burgdorferi ZS7 proteome has enabled insilico analysis of protein sequences for the identification of drug targets and vaccine targets. In this study, 272 essential proteins were identified out of which 42 proteins were unique to the microorganism. The study identified 15 membrane localized drug targets. Amongst these 15, molecular modeling and structure validation of the five membrane localized drug target proteins could only be achieved because of the low sequence identity of the remaining proteins with RCSB structures. These 3D structures can be further characterized by invitro and invivo studies for the development of novel vaccine epitopes and novel antibiotic therapy against Borrelia burgdorferi.

Conventional therapies have been useful in principle for the treatment of Multiple Myeloma; still there is no proper cure for the disease. Towards this quest, we aimed to utilize the computational resources to find out novel targets and their drug molecules. We found out that semaphorin 3A (SEMA3A) has a role in the progression of the disease and the complications associated with the disease. Further investigations into the problem, we established that there is no experimental structure available for the protein in the available data sources. Hence, our work stems from the building of a homology model of the receptor using SWISSMODEL workspace. We performed the model validation to verify the obtained model through which the results gave us a strong confidence level of our model. Further we performed the primary & secondary prediction to provide more insights into the selected receptor. The results identified the receptor as stable in nature. Docking studies were performed for the receptor, taking the available market drugs for multiple Myeloma as ligands. We included herbal ligands which have been shown to be effective against the treatment of the disease in literature. We took 11 available FDA approved drugs and 7 herbal compounds for the purpose of molecular docking. Our results clearly revealed that the herbal drugs are better lead compounds for the treatment of the disease. They also have minimal side effects when administered. The herb, GYNOSAPONIN with maximum negative energy showed good binding energy (-423.51). This can be subjected to experimental validation.

Aim: This study was conducted to detect the mecA gene polymorphism in ovine wounds and its possible association
with the structure and function of penicillin binding protein A2 (PBP2A).
Methods: One genetic locus of 1,967 bp that covered the majority of the coding regions of the mecA gene within
methicillin-resistant Staphylococcus aureus (MRSA) DNA sequences was designed.
Results: In addition to standard microbiological tests, PCR-sequencing reactions and phylogenetic analyses confirmed
the identity of the targeted MRSA bacteria. Seven novel missense SNPs, including N57T, N115Y, D120N, D139N,
G152V, E189K, and F211V, were observed in the mecA amplicons. Multiple state-of-the-art in silico tools were utilized
to assess the consequences of each observed SNP in terms of its effect on the corresponding PBP2A protein structure
and function. It was shown that some MRSA isolates exhibited a highly PBP2A-damaging SNP, G152V, which showed
an entirely deleterious effect on the PBP2A. Furthermore, G152V induced an alteration in the PBP2A interaction with
its receptor, which presumably reduced its affinity to bind with the beta-lactams.
Conclusion: The present report indicated a possible role for the observed deleterious G152V SNP in the reduction of
PBP2A binding with beta-lactams, which has led to a remarkable increase in MRSA’s resistance to antibiotics.
Keywords: Infection, In silico, MecA, Missense, Variations.

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a nuclear receptor family transcription factor that is expressed in several types of cancers. Antiproliferative and proapoptotic actions of PPARγ agonists suggesting that, it could be a promising therapeutic target for the treatment of variety of cancers. Therefore, the main aim of this study is attempt to identify the novel PPARγ agonist from presence of bioactive compounds in ethanolic extract of Cayratia trifolia using GC-MS analysis and Computational molecular simulation studies. The GC-MS analysis revealed that the ethanolic extract of Cayratia trifolia (L.) (whole plant) consist of 20 bioactive compounds which embrace many biological activities against variety of diseases. Molecular docking studies (Glide 5.5 from Schrödinger suite) exposed that, out of 20 bioactive compounds, Cyclopentadecane, 9-Borabicyclo [3.3.1]nonane, 9-(2-propen-1-yloxy)-.1, 4,8,12,16-Tetramethylheptadecan-4-olide, Oxirane and Vitamin E shows the better glide score. ADME properties (QikProp 2.3 from Schrödinger suite) of these bioactive compounds were under the acceptable range. Based on the result it can be concluded that, these bioactive compounds may act as a good agonist for PPARγ. In future it may focus on current discoveries in PPARγ activation and possible anticancer therapeutic option. GOPALAKRISHNAN. Identification of novel PPARγ agonist from GC-MS analysis of ethanolic extract of Cayratia trifolia (L.): a computational molecular simulation studies. J App Pharm Sci, 2014; 4 (09): 006-011.