Antimicrobial resistance has emerged as a major global concern for public health in the last two decades, which tends to compromise the existing drug regimens in treating common or severe infections. According to WHO, three million laboratory-confirmed bacterial infections have been reported from 70 countries in 2019, caused by pathogens of concern. The drug-resistant bacterial strains are characterized as multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan drug-resistant (PDR) based on the different patterns of resistance. It is believed that novel strategies are essentially required to counter and eliminate drug resistance in a cost-effective manner to benefit the world population. Natural compounds and certain dietary agents show potential antimicrobial properties and these have been used since ancient times to treat human infections. In this study, we have investigated the synergistic effects of dietary flavonoids rutin and quercetin with antibiotics gentamicin (an aminoglycoside) and ceftriaxone (a third-generation cephalosporin) against the drug-resistant superbugs; clinical isolates including Escherichia coli (MDR), Proteus mirabilis (XDR), and Klebsiella pneumoniae (PDR). Conventional MIC assay and checkerboard test were used as standard protocols. Our results show that rutin and quercetin restore the antimicrobial activity of the antibiotics against MDR and XDR strains, while no such effect was observed in the case of the PDR strain. Quercetin, which is a aglycone of flavonoid rutin, demonstrates higher synergistic effects with ceftriaxone compared to rutin. Since rutin and quercetin are essentially present in human diets as constituents of fruits and vegetables, their use as nutraceuticals in adjuvant therapies in combination with antibiotics against drug resistance is a promising therapeutic strategy against superbug infections.

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Determining the variations in SARS-CoV-2 variant is considered main factor for understanding the pathogenic mechanisms, aid in diagnosis, prevention and treatment. The present study aimed to determine the genetic variations of SARS-CoV-2. The sequences of SARS-CoV-2 were obtained from National Center for Biotechnology Information (NCBI) and studied according to the time of isolation and their origin. The genome sequence of SARS-CoV-2 accession number NC_045512 which represented the first isolated sequence of SARS-CoV-2 (Wuhan strain) was used as the reference sequence. The obtained genome sequences of SARS-CoV-2 were aligned against this Wuhan strain and variations among nucleotides and proteins were examined. The sequence of SARS-CoV-2 accession number MT577016 showed very low homology 98.75% compared to Wuhan strain NC_045512. The analysis identified 301 nucleotide changes, which correspond to 258 different mutations; most of them 80% (207/258) were missense point mutations followed by 17.1% (44/258) silent point mutations. The critical mutations occurred in viral structural genes; 16.7% (43/258) mutations reported in S gene and 1 missense mutation was observed in E gene. Our finding showed the lowest homology and relatively distant phylogenetic relation of this SARS-CoV-2 variant with Wuhan strain along with high frequency of mutations including those in spike S and envelope E genes.

This study aimed to determine the genetic alterations in the Omicron variants compared to other variants of concern (VOCs) to trace the evolutionary genetics of the SARS-CoV-2 variants responsible for the multiple COVID-19 waves globally. The present study is an in silico analysis determining the evolution of selected 11 VOCs compared to the original Wuhan strain. The variants included six Omicrons and one variant of Alpha, Beta, Delta, Gamma, and Mu. The pairwise alignment with the local alignment search tool of NCBI Nucleotide-BLAST and NCBI Protein-BLAST were used to determine the nucleotide base changes and corresponding amino acid changes in proteins, respectively. The genomic analysis revealed 210 nucleotide changes; most of these changes (127/210, 60.5%) were non-synonymous mutations that occurred mainly in the S gene (52/127, 40.1%). The remaining 10.5% (22/210) and 1.9% (4/210) of the mutations were frameshift deletions and frameshift insertions, respectively. The frameshift insertion (Ins22194T T22195G) led to frameshift deletion (Δ211N). Only four mutations (C241T, C3037T, C14408T, and A23403G) were shared among all the VOCs. The nucleotide changes among Omicron variants resulted in 61 amino acid changes, while the nucleotide changes in other VOCs showed 11 amino acid changes. The present study showed that most mutations (38/61, 62.3%) among Omicron variants occurred in the S gene; and 34.2% of them (13/38) occurred in the receptor-binding domain. The present study confirmed that most of mutations developed by Omicron variants occurred in the vaccine target gene (S gene).