The COVID-19 pandemic caused by SARS-CoV-2 has shown an exponential trend of infected people across the planet. Crediting its virulent nature, it becomes imperative to identify potential therapeutic agents against the deadly virus. The 3-chymotrypsin-like protease (3CLpro) is a cysteine protease which causes the proteolysis of the replicase polyproteins to generate functional proteins, which is a crucial step for viral replication and infection. Computational methods have been applied in recent studies to identify promising inhibitors against 3CLpro to inhibit the viral activity. This review provides an overview of promising drug/lead candidates identified so far against 3CLpro through various in silico approaches such as structure-based virtual screening (SBVS), ligand-based virtual screening (LBVS) and drug-repurposing/drug-reprofiling/drug-retasking. Further, the drugs have been classified according to their chemical structures or biological activity into flavonoids, peptides, terpenes, quinolines, nucleoside and nucleotide analogues, protease inhibitors, phenalene and antibiotic derivatives. These are then individually discussed based on the various structural parameters namely estimated free energy of binding (ΔG), key interacting residues, types of intermolecular interactions and structural stability of 3CLpro-ligand complexes obtained from the results of molecular dynamics (MD) simulations. The review provides comprehensive information of potential inhibitors identified through several computational methods thus far against 3CLpro from SARS-CoV-2 and provides a better understanding of their interaction patterns and dynamic states of free and ligand-bound 3CLpro structures.

The World Health Organization (WHO) report stated that Acinetobacter baumannii had been classified as one of the most important pathogenic bacteria causing nosocomial infection in hospital patients due to multi-drug resistance (MDR). It is vital to find out new bacterial drug targets and annotated their structure and function for the exploration of new anti-bacterial agents. The present study utilized a systematic route to prioritize the potential drug targets that belong to Mur family of Acinetobacter baumannii and identify their homologous proteins using a computational approach such as sequence similarity search, multiple sequence alignment, phylogenetic analysis, protein sequence, and protein structure analysis. From the results of protein sequence analysis of eight Mur family proteins, they divided into three main enzymatic classes namely transferases (MurG, MurA and MraY), ligases (MurC, MurD, MurE, and MurF), and oxidoreductase (MurB). Based on the results of intra-comparative protein sequence analysis and enzymatic classification, we have chosen MurB, MurE, and MurG as the prioritized drug targets from A. baumannii and subjected them for further detailed studies of inter-species comparison. This inter-species comparison help us to explore the sequential and structural properties of homologous proteins in other species and hence, opens a gateway for new target identification and using common inhibitor for different bacterial species caused by various diseases. The pairwise sequence alignment results between A. baumannii’s MurB with A. calcoaceticus’s MurB, A. baumannii’s MurE with A. seifertii’s MurE, and A. baumannii’s MurG with A. pittii’s MurG showed that every group of the proteins are highly similar with each other and they showed sequence identity of 95.7% and sequence similarity of 97.2%. Together with the results of secondary and three-dimensional structure predictions explained that three selected proteins (MurB, MurE, and MurG) from A. baumannii and their related proteins (AcMurB, AsMurE, and ApMurG) belong to mixed αβ class and they are very similar.

Salmonella are the major pathogenic bacteria in humans as well as in animals. Salmonella species are leading causes of acute gastroenteritis in several countries and salmonellosis remains an important public health problem worldwide, particularly in the developing countries. Isolation of Salmonella from a wide range of sources suggests that Salmonella is widespread in food animals and meat products and underlines the necessity for a joint and coordinated surveillance and monitoring programs for salmonellosis and other major food borne zoonotic diseases. Food animals harbor a wide range of Salmonella and so act as sources of contamination, which is of paramount epidemiological importance in non-typhoid human salmonellosis. Salmonellosis is more aggravated by the ever increasing rate of antimicrobial resistance strains in food animals. The high prevalence and dissemination of multidrug resistant (MDR) Salmonella have become a growing public health concern. Multidrug resistant (MDR) strains of Salmonella are now encountered frequently and the rates of multidrug resistance have increased considerably in recent years. Food animal consumption is a potential cause for antimicrobial resistant Salmonella illnesses besides, the common factors such as overcrowding, poverty, inadequate sanitary conditions, and poor personal hygiene. Practicing good sanitary measures, extensive education programs for proper hygiene and improvement of managements are solutions to eliminate the high bacteriological load as well as prevalence of Salmonella in cattle carcass. Furthermore, restricting the use of antimicrobial agents in food animals, designation of multidrug-resistant Salmonella as an adulterant in ground beef, improving the mechanisms for product trace-back investigations and wise and discriminate use of antimicrobials should be practiced to combat the ever increasing situation of antimicrobial resistance. So, this review used for updating information on their prevalence and resistance patterns is very important to suggest the acceptance of the carcass in relation to the standards and for proper selection and use of antimicrobial agents in a setting.