Chirag J Gohil

Drug resistance in tuberculosis has been shown to result from spontaneous mutation in several chromosomal genes of M.Tuberculosis. Mutation may reduce the medications' capacity to bind to the target genes. In many patients polydrug resistance, multidrug resistance, rifampicin resistance (RR) and extensive drug resistance (XDR) were seen. The diagnosis of drug-resistant TB in HIV-ith mono- or positive persons is more difficult and may be confused with other pulmonary or systemic infections. Management of patients wpoly-resistant TB will be done with standard first line chemotherapy. Treatment of latent infection for people suffering from multidrug resistant bacilli is problematic because the only cure by isoniazid and rifampicin. In the recent cases of severe hepatotoxicity associated with preventive treatment comprising either pyrazinamide and rifampicin or pyrazinamide and fluoroquinolone. The use of dilatory fluoroquinolones, such as moxifloxacin, remarkable improved treatment outcomes of XDR-TB. Keywords: Tuberculosis, Drug­resistance TB, Mechanism of drug resistance

Tuberculosis is a disease caused by bacteria spread from person to person through air. TB usually affects the lungs, but it can also affect other parts of the body, such as brain or kidney. Global surveillance has shown that drug resistant TB is widespread and is now a treat to tuberculosis control programs in many countries. This review describes treatment of tuberculosis and the drug resistance problem in India. Keywords: Tuberculosis, Treatment, Antibiotics, Drug resistance TB in India

MDM2 inhibitors class of anti-neoplastic drugs has been evolve after the successful discovery of the nutlins and other potent inhibitors. MDM2 inhibitors can specifically target the tumour cells in the body, by selectively reactivating the inhibited p53 function in the tumour cells.None of the compound of this class has been entered into the market till date, all are under clinical trials. Hence, various researcher classifies them according to their p53 topology mimetic property and as per their peptide type or non-peptide type.Synthetic peptide type of inhibitors can mimic the conformation of p53 helix. Whereas, small organic molecule (non-peptide) type of MDM2 inhibitors have been further subdivided as Non ?-helix mimetics (small molecule inhibitors) and ?-helix mimetics. In a line with synthetic inhibitors, many potent MDM2 inhibitors are derived from the natural origin (marine, fungus). Therefore, keeping in a view of all these characteristics, here we have classified them as per best of our knowledge. Keywords: Cancer, Apoptosis, p53 protein, MDM2 protein, types of MDM2 inhibitors

Novel corona virus or Covid-19 is a single stranded RNA virus. It is the part of the corona virus family. The latest pandemic covid-19 is causes by the novel corona virus. The symptoms of novel corona virus infection are varying from mild to chronic. The specific and effective treatment of the novel corona virus is not available yet. Since SARS-CoV and MERS-CoV are also part of the corona virus family and it is similar to novel corona virus, so we can identify the drug target by studying them. Novel Corona virus has some essential structural proteins like spikes, envelop, membrane and nucleocaspid proteins, hence we can target that proteins by drugs. In SARS-CoV, most import protein for the host cell attachments and fusion into the host cells is spikes proteins (same as of in novel corona virus). Therefore it is potential target for the development of anti-corona drugs. Including the spikes proteins, other prominent targets of novel corona virus are haemagglutinin esterase, helicase and protease. On the other hand, utilizing the knowledge and therapy of the alternative medicinal systems like ayurvedic and homeopathic may provide better alternative for the treatment of novel corona virus/covid-19. Keywords: Novel corona virus, Covid-19, SARS-CoV, MERS-CoV, Spikes proteins, Anti-corona drugs targets.

Cancer is a tumorous disease, which involves the unwanted cell growth and cell division. The imbalance or inactivity of the apoptosis in the body is responsible for the occurrence of tumour and cancer. This apoptosis is regulated by the p53 protein, which is tumour suppressor protein. In the cancer cells, this p53 has been inhibited by the MDM2 protein. MDM2 interact with the p53 and make it inactive. This p53-MDM2 interaction is responsible for the cancer genesis. If we target this interaction, then we can initiate the apoptosis in the cancer cells by making the free p53 protein. There are many strategies to inhibit this p53-MDM2 interaction. Among them non-peptidic small molecule inhibitors are the convenient approach. Small molecule inhibitors have a three pocket binding, so they bind with p53 binding pocket (Trp 23, Leu 26 and Phe 19), present in the MDM2 protein. That is how it spares the p53 protein and makes it available in the cancer cells. Hence, small molecule inhibitors successfully inhibit the p53-MDM2 interaction and can initiate the apoptosis in the cancer cells, which are having the un-mutated p53 protein. They can’t inhibit this interaction in the cells which contains the mutated or deleted p53 protein. Hence, this limitation must be addressed. Many of the small molecular MDM2 inhibitors have been successfully entered into the clinical trials and they are performing well. The clinical data indicate that the small molecular MDM2 inhibitors are having very low toxicity to the normal cells. And they are non-genotoxic so they are near to nontoxic to the normal cells. But none of the any small molecule MDM2 inhibitor has been enters into the market yet. So till then, it has required advancement and research to make more selective and specific for the cancer cells over the normal cells. Keywords: Cancer, Apoptosis, p53 protein, MDM2 protein, p53-MDM2 interaction, Three pocket binding, Small molecule p53-MDM2 interaction inhibitors.