Epidemiology of Multidrug Resistance among Salmonella enterica serovars typhi and paratyphi A at a Tertiary Pediatric Hospital in India Over a Decade; In-silico Approach to Elucidate the Molecular Mechanism of Quinolone Resistance.

BACKGROUND: Enteric fever caused by Salmonella enterica serovar typhi and Salmonella enterica serovar paratyphi A remains one of the most common causes of community-acquired bloodstream infection among children in India. Multidrug resistance is emerging and is a cause of concern as it affects the choice of treatment in enteric fever. METHOD: In this study, a 10-year analysis of resistance patterns was done along with in-silico homology modeling and molecular docking to understand the commonly occurring quinolone resistance. RESULTS: A total of 1010 cases of blood culture-confirmed enteric fevers (S. typhi n=849; S. paratyphi A n=161) were recorded at the study hospital during the period from 2011-2020. Multidrug resistance among cases of S. typhi was 2.12 %, whereas it was completely absent among cases of S. paratyphi A. Fluoroquinolone resistance was high (>95%) throughout the study period. Resistance to ampicillin, chloramphenicol and co-trimoxacole was low (<3%) among S. typhi cases. No deaths were observed among study participants. Molecular docking analysis showed that quinolone had less binding affinity to mutated gyrase A than to its wild type for both S. typhi and S. paratyphi A. CONCLUSION: Quinolone resistance was high among cases of enteric fever, whereas no resistance was observed among third-generation cephalosporins. In-silico studies indicated that a mutation in gyrase A might be the cause of the gradual increase in ciprofloxacin resistance over the study period.

Potential combination therapy using twenty phytochemicals from twenty plants to prevent SARS- CoV-2 infection: An in silico Approach.

Covid 19 caused by novel strain SARS- CoV-2 has become a pandemic due to its contagious nature of infection. It enters by binding with ACE2 receptor present on the outer surface of a cell by cleaving S1/S2 with proteolytic protein Furin. Further viral replication or transcription then takes place with the help of main protease 3CLpro and polymerase RdRp. This in silco study was carried out to block ACE2, Furin, 3CLpro and RdRP with various phytochemicals to prevent SARS- CoV-2 entry and replication or transcription. Twenty different phytochemicals were screened to understand the drug-likeliness obeying Lipinski's rule 5 and further, molecular docking was performed using these phytochemicals to block their respective target proteins. All the phytochemicals follow Lipinski's rule of five and molecular docking result shows best binding affinity of Podofilox - 7.54 kcal/mol with ACE2, Psoralidin - 8.04 kcal/mol with Furin, Ursolic acid - 8.88 kcal/mol with 3CLpro and Epiafzelechin - 8.26 kcal/mol with RdRp. Thus, blocking two human receptors ACE2 and Furin with Podofilox and Psoralidin respectively may prevent the viral entry into the cells. Also blocking viral proteins 3CLpro and RdRp with Ursolic acid and Epiafzelechin may prevent viral replication or transcription. Using this combination therapy of blocking the receptors responsible for viral entry and viral proteins responsible for replication or transcription may prevent SARS- CoV-2 infection.