Binding and drug displacement study of colchicine and bovine serum albumin in presence of azithromycin using multispectroscopic techniques and molecular dynamic simulation.

The binding and displacement interaction of colchicine and azithromycin to the model transport protein bovine serum albumin (BSA) was evaluated in this study. Azithromycin, a macrolide antibiotic, has antiviral properties and hence, has been used concomitantly with hydroxychloroquine against SARS-CoV-2. Colchicine, a natural plant product is used to treat and prevent acute gout flares. Some macrolide antibiotics are reported to have fatal drug-drug interactions with colchicine. The displacement interaction between colchicine and azithromycin on binding to BSA was evaluated using spectroscopic techniques, molecular docking and molecular dynamic simulation studies. The binding constant recorded for the binary system BSA-colchicine was 7.44 × 104 whereas, the binding constant for the ternary system BSA-colchicine in presence of azithromycin was 7.38 × 104 and were similar. Azithromycin didn't bind to BSA neither did it interfere in binding of colchicine. The results from molecular docking studies also led to a similar conclusion that azithromycin didn't interfere in the binding of colchicine to BSA. These findings are important since there is possibility of serious adverse event with co-administration of colchicine and azithromycin in patients with underlying gouty arthritis and these patients need to be continuously monitored for colchicine toxicity.

Structure, interactions and membrane topology of HIV gp41 ectodomain sequences.

The gp41 type I membrane protein is part of the trimeric Env complex forming the spikes at the HIV surface. By interacting with cellular receptors, the Env protein complex initiates the infectious cycle of HIV. After the first contact has been established Env disassembles by shedding gp120 while the remaining gp41 undergoes a number of conformational changes which drive fusion of the cellular and the viral membranes. Here we investigated the membrane interactions and oligomerization of the two gp41 heptad repeat domains NHR and CHR. While these are thought to form a six-helix bundle in the post-fusion state little is known about their structure and role during prior fusion events. When investigated in aqueous buffer by CD and fluorescence quenching techniques the formation of NHR/CHR hetero-oligomers is detected. An equilibrium of monomers and hetero-oligomers is also observed in membrane environments. Furthermore, the partitioning to POPC or POPC/POPG 3/1 vesicles of the two domains alone or in combination has been studied. The membrane interactions were further characterized by 15N solid-state NMR spectroscopy of uniaxially oriented samples which shows that the polypeptide helices are oriented parallel to the bilayer surface. The 31P solid-state NMR spectra of the same samples are indicative of considerable disordering of the membrane packing. The data support models where NHR and CHR insert in the viral and cellular membranes, respectively, where they exhibit an active role in the membrane fusion events.