Leishmaniasis is one of the neglected tropical diseases (NTDs), mainly affecting impoverished communities and having varied ranges of pathogenicity according to the diverse spectrum of clinical manifestations. It is endemic in many countries and poses major challenges to healthcare systems in developing countries. Despite the fact that most of the current mono and combination therapies are found to be failures, clear perception of gene essentiality for parasite survival are now desideratum to identify potential biochemical targets through selection. Here we used the metabolic network of L. major, to perform a comprehensive set of in silico deletion mutants and have systematically recognized a clearly defined set of essential proteins by combining several essential criteria. In this paper we summarize the efforts to prioritize potential drug targets up to a five-fold enrichment compared with a random selection.

The COVID-19 pandemic has become a global health challenge because of the emergence of distinct variants. Omicron, a new variant, is recognized as a variant of concern (VOC) by the World Health Organization (WHO) because of its higher mutations and accelerated human infection. The infection rate is strongly dependent on the binding rate of the receptor binding domain (RBD) against human angiotensin converting enzyme-2 (ACE2 human ) receptor. Inhibition of protein–protein (RBDs (SARS-CoV-2/omicron) -ACE2 human ) interaction has been already proven to inhibit viral infection. We have systematically designed ACE2 human -derived peptides and peptide mimetics that have high binding affinity toward RBD omicron . Our peptide mutational analysis indicated the influence of canonical amino acids on the peptide binding process. Herein, efforts have been made to explore the atomistic details and events of RBDs (SARS-CoV-2/omicron) -ACE2 human interactions by using molecular dynamics simulation. Our studies pave a path for developing therapeutic peptidomimetics against omicron.

The pandemic of COVID- 19 has become the global health challenge due to the emergence of new variants. The Receptor binding domain (RBD) of spike protein that makes direct interaction with ACE-2 has shown unique mutated residues in most of the variants of concern (VOC). Recently WHO declared the Omicron (B.1.1.529) as VOC considering it as a highly mutated variant which includes a total of 60 mutations out of which 15 mutations occurred in RBD region of SARS-CoV-2. Inhibition of Protein-protein (Omicron RBD-h-ACE2) interaction was already proved to inhibit the viral infection. In this study, by using molecular dynamic simulations efforts are made to explore the atomistic details of Omicron RBD-h-ACE2 interaction. Based on MD simulations, h-ACE2 motif is found to be interacting with omicron RBD domain. Interaction analysis had provided key residues interacting with Omicron-RBD that helped to extract h-ACE2 peptide. Here, rational design of the peptides that have resemblance with h-ACE2 is done and the peptide library is subjected for inhibition studies against Omicron-RBD. The current study helped to identify the significant peptides that can inhibit Omicron-RBD. Altogether the performed studies will provide an opportunity to develop potential therapeutic peptidomimetics effective against Omicron variant of SARS-CoV-2.