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AbstractA thorough investigation of the water permeability of H. fossilisaquaporin 1 (hfAQP1) in a hypertonic environment can provide a useful insight into the understanding of the underlying molecular mechanism of its high tolerance to salinity. Here, we constructed a 3 D homology model of hfAQP1 by taking Bos taurusAQP1, AQP0, and human AQP2 as templates using I-TASSER. The model obtained has similar structural organizations with mammalian AQP1s in all aspects. We investigated the water permeability of the modeled hfAQP1 in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membrane under neutral and 100 mM hypersalinity by subjecting each system to a 100 ns molecular dynamics simulation. Our results show that hypersalinity hinders water permeation across the membrane through the hfAQP1 channel. A change in the intermolecular distance between key residues of the ar/R selectivity filter along with charge redistribution resulted in the accommodation of only 2–6 water molecules inside the channel at once under hypersaline conditions. We investigated the mRNA expression pattern of hfaqp1in osmoregulatory organs of H. fossilisin response to 100 mM hypertonicity by using qPCR analysis. The transcript was downregulated in kidney and GI tract, but upregulated in the Gills. Thus, the catfish survive in a hypertonic environment by reducing the transport of water in its cellular systems and downregulating the expression of the hfaqp1gene. The results observed in our study can shed more light on the functionality of AQP1 in catfishes under salinity stress and aid in future researches on solving more gating mechanisms involved in its regulation.Communicated by Ramaswamy H. Sarma

AbstractThe Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which was first reported in Wuhan province of China, has become a deadly pandemic causing alarmingly high morbidity and mortality. In the absence of new targeted drugs and vaccines against SARS-CoV-2 at present, the choices for effective treatments are limited. Therefore, considering the exigency of the situation, we focused on identifying the available approved drugs as potential inhibitor against the promising Coronavirus drug target, the Main Protease, using computer-aided methods. We created a library of U. S. Food and Drug Administration approved anti-microbial drugs and virtually screened it against the available crystal structures of Main Protease of the virus. The study revealed that Viomycin showed the highest -CDocker energy after docking at the active site of SARS-CoV-2 Main Protease. It is noteworthy that Viomycin showed higher -CDocker energy as compared to the drugs currently under clinical trial for SARS-CoV-2 treatment viz.Ritonavir and Lopinavir. Additionally, Viomycin formed higher number of H-bonds with SARS-CoV-2 Main Protease than its co-crystallised inhibitor compound N3. Molecular dynamics simulation further showed that Viomycin embedded deeply inside the binding pocket and formed robust binding with SARS-CoV-2 Main Protease. Therefore, we propose that Viomycin may act as a potential inhibitor of the Main Protease of SARS-CoV-2. Further optimisations with the drug may support the much-needed rapid response to mitigate the pandemic.Communicated by Ramaswamy H. Sarma

PagN is a highly immunogenic 27-kDa outer membrane adhesin present in SalmonellaTyphi. It plays a major role in the pathogenesis of typhoid fever and has emerged as a strong vaccine candidate. In this report, we predict the three-dimensional structure of PagN and describe the conformational dynamics associated with its four extracellular loops based on two 100-ns molecular dynamics simulations at 300 and 310 K. The formation and deformation of the secondary structures on these loops were also investigated during the simulations which revealed loops L1 and L2 to be highly flexible, whereas the relative flexibility of loops L3 and L4 was minimal. Essential dynamics and principal component analysis deciphered more realistic dynamic behaviours of the loops, particularly at 310 K. Moreover, our epitope predictions suggest that the antigenic peptides for B-cell recognition are located within the loops L1 and L2, while those for T-cell recognition are located within the loops L3 and L4. The binding specificities of the antigenic peptides towards specific human MHC-I and MHC-II HLA alleles closely resembled the stability of the loops L3 and L4 inferred from the simulations. Finally, we identified potential antigenic peptides in the flexible (L1 and L2) as well as stable (L3 and L4) regions of PagN for both B- and T-cell recognitions, which can help in developing effective sub-unit vaccines.