Dengue virus belongs to the virus family Flaviviridae. Dengue hemorrhagic disease caused by dengue virus is a public health problem worldwide. The viral non structural 2B and 3 (NS2B-NS3) protease complex is crucial for virus replication and hence, it is considered to be a good anti-viral target. Leaf extracts from Carica papaya is generally prescribed for patients with dengue fever, but there are no scientific evidences for its anti-dengue activity; hence we intended to investigate the anti-viral activity of compounds present in the leaves of Carica papaya against dengue 2 virus (DENV-2). We analysed the anti-dengue activities of the extracts from Carica papaya by using bioinformatics tools. Interestingly, we find the flavonoid quercetin with highest binding energy against NS2B-NS3 protease which is evident by the formation of six hydrogen bonds with the amino acid residues at the binding site of the receptor. Our results suggest that the flavonoids from Carica papaya have significant anti-dengue activities.AbbreviationsADME - Absorption, distribution, metabolism and excretion, BBB - Blood brain barrier, CYP - Cytochrome P450, DENV - – Dengue virus, DHF - Dengue hemorrhagic fever, DSS - Dengue shock syndrome, GCMS - – Gas chromatography- Mass spectrometry, MOLCAD - Molecular Computer Aided Design, NS - Non structural, PDB - Protein data bank, PMF - Potential Mean Force.

Bacterial resistance to β-lactam antibiotics poses a serious threat to human health. Penicillin binding proteins (PBPs) and β-lactamases are involved in both antibacterial activity and mediation of β-lactam antibiotic resistance. The two major reasons for resistance to β-lactams include: (i) pathogenic bacteria expressing drug insensitive PBPs rendering β-lactam antibiotics ineffective and (ii) production of β-lactamases along with alteration of their specificities. Thus, there is an urgent need to develop newer β-lactams to overcome the challenge of bacterial resistance. Therefore the present study aims to identify the binding affinity of β-lactam antibiotics with different types of PBPs and β-lactamases. In this study, cephalosporins and carbapenems are docked into PBP2a of Staphylococcus aureus, PBP2b and PBP2x of Streptococcus pneumoniae and SHV-1 β-lactamase of Escherichia coli. The results reveal that Ceftobiprole can efficiently bind to PBP2a, PBP2b and PBP2x and not strongly to SHV-1 β-lactamase. Furthermore, molecular dynamics (MD) simulations are performed to refine the binding mode of the docked complex structure and to observe the differences in the stability of free PBP2x and Ceftobiprole bound PBP2x. MD simulation supports the greater stability of the Ceftobiprole-PBP2x complex compared to free PBP2x. This work demonstrates that potential β-lactam antibiotics can efficiently bind to different types of PBPs for circumventing β-lactam resistance and opens avenues for the development of newer antibiotics that can target bacterial pathogens.

Klebsiella pneumoniae strains producing extended-spectrum β-lactamases (ESBL) exhibit resistance to antibiotic classes. The production of ESBLs (TEM-1, TEM-2, SHV-1, OXA-1) results in resistance to ampicillin, ticarcillin, piperacillin and cephalosporins. High levels of β-lactamases leads to development of resistance to β-lactamase inhibitors. The present study deals with characterizing antimicrobial resistance pattern among septicemia causing K. pneumoniae and the prevalence of inhibitor resistant OXA-1 β-lactamase genes among them. Of 151 study isolates, 59 were resistant to piperacillin/tazobactam and these isolates were further selected for blaOXA-1 screening. Amplification of β-lactamases genes by conventional PCR showed the presence of blaOXA-1 genes among 12 K. pneumoniae (20.3%) isolates. OXA-1 β-lactamase producing strains were found to be resistant to piperacillin/tazobactam(100%), levofloxacin (91.6%), amikacin (75%), cefoxitin (50%), ertapenem (25%), imipenem (16.6%) and meropenem (16.6%); all were susceptible to tigecycline. 3D models of OXA-1 β-lactamase were generated and docking was performed with various β-lactam antibiotics. Molecular docking (MD) revealed the molecular basis of drug sensitivity. MD simulation results clearly confirmed the notable loss in stability for tigecycline-blaOXA-1 complex. Findings of the present study will provide useful insights for understanding the mechanism of resistance and help with strategies for the development of new antibiotics. The conventional PCR assay designed in this study can be routinely used in clinical microbiology laboratories to determine the blaOXA-1genes.

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An analysis of wind and wave data collected in the coastal region of Goa, west coast of India, during fair weather season reveals a distinct and systematic diurnal variation in wind speed, wave height and wave period, especially simultaneous increase in wave height and decrease in wave period with increase in local wind speeds due to sea breeze system. During a typical daily cycle, the wave height reaches its peak early in the afternoon, then it decays progressively back to the swell conditions within 5 or 6 hours. Measured wave spectra distinctly bring out salient features of deep water swell and wind seas generated by the local sea breeze. Numerical simulations reproduce the characteristics of this daily cycle. The exposure of Goa coast to long distant swells from the southwest and to the local wind seas from the northwest leads to complex cross-sea conditions.

Upper respiratory tract infection (URTI) is an acute infection which involves the upper respiratory tract: nose, sinuses, tonsils and pharynx. URT infections are caused mainly by pathogenic bacteria like Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. Conventionally, β-lactam antibiotics are used to treat URT infections. Penicillin binding proteins (PBPs) catalyze the cell wall synthesis in bacteria. β-Lactam antibiotics like Penicillin, Cephalosporins, Carbapenems and Monobactams inhibit bacterial cell wall synthesis by binding with PBPs. Pathogenic bacteria have efficiently evolved to resist these β-lactam antibiotics. New generation antibiotics are capable of inhibiting the action of PBP due to its new and peculiar structure. New generation antibiotics and Penicillin derivatives are selected in this study and virtually compared on the basis of interaction studies. 3-Dimensional (3D) interaction studies between Lactivicin, Cefuroxime, Cefadroxil, Ceftaroline, Ceftobiprole and Penicillin derivatives with PBPs of the above-mentioned bacteria are carried out. The aim of this study was to suggest a potent new generation molecule for further modification to increase the efficacy of the drug for the URTI.

35Actinomycetes isolates collected from different environments were screened for 36 antiviral activity against WSSV. One isolate designated as CAHSH-2 showed antiviral 37 activity against WSSV at the concentration of 0.2 mg per shrimp. The laboratory trial of 38 determining antiviral activity of ethyl acetate extract (EtOAcE) of CAHSH-2 against WSSV 39 was carried out 21 times since 2014. CAHSH-2 isolate which showed antiviral activity was 40 characterized and identified as Streptomyces ghanaensis like strain. Among the five fractions 41 obtained from EtOAcE of potential actinomycetes isolate, F1 was found to have strong 42 antiviral activity. The F1A and F1B sub-fractions from F1 fraction were subjected to GC-MS, 43 FTIR, 1 H and 13 C NMR analyses and, the compounds identified were di-n-octyl phthalate and 44 bis (2-methylheptyl) phthalate, respectively. Among these compounds, di-n-octyl phthalate 45 showed strong antiviral activity against WSSV. Molecular docking studies revealed that di-n-46 octyl phthalate was found to have high binding affinity with VP26 and VP28 proteins of 47 WSSV, whereas the bis (2-methylheptyl) phthalate showed low binding affinity with VP26 48 and VP28. The antiviral activity of EtOAcE of actinomycetes against WSSV was confirmed 49 by PCR, RT-PCR, Western blot and ELISA. The EA extract of active isolate was found to be 50 non-toxic to Artemia, post-larvae and adult Litopenaeus vannamei. 51 Importance 52 53White spot syndrome virus (WSSV) is an important shrimp viral pathogen and 54 responsible for huge economic loss to shrimp culture industry worldwide including India. The 55 global loss due to WSSV has been estimated about USD 10 billion and the loss continues at 56 the same extent even now. Various strategies have been followed to prevent or control 57 diseases of aquatic animals. In spite of various preventive and control strategies, WSSV has 58 been still persisting for more than two decades. No control strategies have so far been evolved 59 to put a break to WSSV. In this situation, an attempt was made in the present work to screen 60 some actinomycetes isolates for antiviral activity against WSSV. Among these isolates, one 61 isolate identified as Streptomyces ghanaensis like isolate CAHSH-2 showed activity against 62 WSSV. This article gives the information about the antiviral compound against WSSV and 63 the mechanism of viral inhibition. 64 65 66

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