Trends in Molecular Aspects and Therapeutic Applications of Drug Repurposing for Infectious Diseases

The pharmaceutical industry has undergone a severe economic crunch in antibiotic discovery research due to evolving bacterial resistance along with enormous time and money that gets consumed in de novo drug design and discovery strategies. Nevertheless, drug repurposing has evolved as an economically safer and excellent alternative strategy to identify approved drugs for new therapeutic indications. Virtual high throughput screening (vHTS) and phenotype-based high throughput screening (HTS) of approved molecules play a crucial role in identifying, developing, and repurposing old drug molecules into anti-infective agents either alone or in synergistic combination with antibiotic therapy. This chapter briefly explains the process of drug repurposing/repositioning in comparison to de novo methods utilizing vHTS and HTS technologies along with ‘omics- and poly-pharmacology-based drug repurposing strategies in the identification and development of anti-microbial agents. This chapter also gives an insightful survey of the intellectual property landscape on drug repurposing. Further, the challenges and applications of drug repurposing strategies in the discovery of anti-infective drugs are exemplified. The future perspectives of drug repurposing in the context of anti-infective agents are also discussed

High-Throughput Screening for Drug Discovery toward Infectious Diseases: Options and Challenges

The increase in the number of antibiotic-resistant microbial strains makes it evident to discover and develop newer efficacious anti-infective drugs. High-throughput screening (HTS) is a robust technology that plays a crucial role in identifying novel anti-infective lead compounds. This chapter briefly explains the role of virtual HTS (vHTS) and HTS technologies in lead identification using various categories of chemical libraries through structure-based drug design, ligand-based drug design, in vitro cell-based assay, and biochemical assay approaches involved in the process of drug design and discovery. The chapter also gives an insightful survey of the technologies such as fluorescence, luminescence, and atomic absorbance used for the detection of biological responses in the HTS bioassays. Applications of HTS, reverse pharmacology, current challenges, and future perspectives of HTS in the pharmaceutical and biotechnology industry are discussed in the context of anti-infective drug design, discovery, and development

Recombinant vaccines for COVID-19

SARS-CoV-2, the causative agent of COVID-19, has imposed a major public health threat, which needs effective therapeutics and vaccination strategies. Several potential candidate vaccines being rapidly developed are in clinical evaluation. Considering the crucial role of SARS-CoV-2 spike (S) glycoprotein in virus attachment, entry, and induction of neutralizing antibodies, S protein is being widely used as a target for vaccine development. Based on advances in techniques for vaccine design, inactivated, live-vectored, nucleic acid, and recombinant COVID-19 vaccines are being developed and tested for their efficacy. Phase3 clinical trials are underway or will soon begin for several of these vaccines. Assuming that clinical efficacy is shown for one or more vaccines, safety is a major aspect to be considered before deploying such vaccines to the public. The current review focuses on the recent advances in recombinant COVID-19 vaccine research and development and associated issues

Rectal prolapse in children: Laparoscopic suture rectopexy is a suitable alternative

<b>Aim</b> : To study the clinical outcome of laparoscopic suture rectopexy (LSRP) in children with persistent rectal prolapse (PRP). <b>Materials and Methods</b> : Nineteen cases of PRP were managed with LSRP from February 2005 to August 2009. <b>Results</b> : All were followed up for an average duration of 6 months. Only one child had recurrence and was managed with sclerotherapy. <b>Conclusion</b> : LSRP is safe, feasible in children and gives satisfactory results

Clinical spectrum and prognostic markers of multi-system inflammatory syndrome in children hospitalised in Northern India

Background: Multi-system inflammatory syndrome in children (MIS-C) is characterized by hyper-inflammation and multi-organ dysfunction with antecedent SARS-CoV-2 infection. To describe clinical, laboratory characteristics and outcome of children with MIS-C in a low-middle-income-country and to evaluate factors associated with mortality. Methods: Cases ( 50 mg/L [aOR 9.6 (95% CI 1.8–50.9)] and Prothrombin Time (PT) > 17 seconds at presentation [aOR 13.6 (95% CI 1.6–118.9)] to be independently associated with mortality. Need of MV emerged as independent predictor of mortality on Model 2. Conclusions: Children with MIS-C having high CRP and PT at presentation are at increased odds of dying and require intensive monitoring