Bromotyrosine derivatives from marine sponges inhibit the HIV-1 replication in vitro

Abstract

Background: Human immunodeficiency virus type 1 (HIV-1) infection and Acquired immunodeficiency syndrome are mayor global public health issues. HIV-1 infection is now manageable as a chronic disease thanks to the development of antiretroviral therapy; however, the existence of HIV drug resistance and collateral effects have increased the search for therapeutic alternatives. Compounds of marine resources have been studied for their antiviral potential. Objectives: To evaluate the antiviral activity of isolated bromotyrosine-derivative compounds from the Colombian marine sponges, Verongula rigida and Aiolochoria crassa against HIV-1 infection in vitro. Methods: Cytotoxicity of 11 bromotyrosine-derivative compounds was determined by the MTT assay. Inhibition of HIV-1 replication was performed using the U373-MAGI cell line, which was infected with recombinant green fluorescent protein (GFP)-expressing viruses pseudotyped, in the presence or absence of the compounds. The percentage of infected cells was evaluated by flow cytometry. In addition, the inhibition of reverse transcription and nuclear import was determined by quantification of early and late reverse transcription products and 2-LTR circles, respectively, using quantitative PCR. Results: Aeroplysinin-1, purealidin B and 3-bromo-5-hydroxy-Omethyltyrosine inhibited the HIV-1 replication in a dose-dependent manner, with a median maximum percentage of inhibition of 74% (20 μM), 57% (80 μM) and 47% (80 μM), respectively. Importantly, none of these concentrations were cytotoxic. Aeroplysinin-1, 19-deoxyfistularin 3, purealidin B, fistularin 3 and 3-bromo-5-hydroxy-O-methyltyrosine inhibited the nuclear import efficiently; while 3,5-dibromo-N,N,N,O-tetramethyltyraminium, aeroplysinin-1, purealidin B, fistularin 3 and 3-bromo-5-hydroxy-Omethyltyrosine inhibited X4 HIV-1 cell entry with a median maximum percentage of inhibition ranging between 2 to 30%. Conclusions: Aeroplysinin-1, 19-deoxyfistularin 3, purealidin B, fistularin 3 and 3-bromo-5-hydroxy-O-methyltyrosine inhibited HIV replication at different steps. This study opens the possibility of chemically synthesizing these compounds and evaluating them as alternative therapies against HIV-1.

Marine Sponge-Derived Secondary Metabolites Modulate SARS-CoV-2 Entry Mechanisms

“…Furthermore, Avarol prevents the suppression of the UAG termination codon at the gag-pol junction of the retroviral genome of Moloney murine leukemia virus (Mo-MuLV) [41] and human immu-nodeficiency virus (HIV) [42], which most likely lead to a functional consequence, inhibiting the readthrough of the retroviral protease gene that overlaps the pol and gag genes. Aeroplysinin-1 has also previously been shown to inhibit HIV replication by inhibiting cell entry, reverse transcription and nuclear import [43].…”

Marine Bromotyrosine Derivatives in Spotlight: Bringing Discoveries and Biological Significance

“…[38] ianthelliformisamine A (7) Selective activity on P. aeruginosa, (MIC = 35 µM) and 77% inhibition of S. aureus at 175 µM [18] ianthelliformisamine B (8) Minor inhibition of P. aeruginosa (80% at 87.5 µM)…”

“…Notably, ianthelliformisamines A (7), B (8), and C (79) constitute exceptions, as they demonstrated inhibitory effects on the growth of Pseudomonas aeruginosa. The presence of the spermine moiety in ianthelliformisamines A (7) and C (79) appears to be crucial for their activity. Notably, ianthelliformisamine B (8), which contains a spermidine moiety instead of spermine, demonstrates a significant reduction in activity, suggesting the importance of the spermine moiety for activity against P. aeruginosa [18].…”

“…All the bromotyrosine derivatives isolated before 2004 were thoroughly reviewed in 2005 by J. Peng et al [ 4 ]. Moreover, bromotyrosines have been extensively researched, with a total of 24 reviews published covering various aspects related to bromotyrosines, including their biological effects [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ], their roles in biological processes [ 16 ], and synthetic methodologies [ 17 ]. Our review comprehensively covers newly identified bromotyrosines from 2004 to 2023, examining both their structural features and related activities.…”

first, the next, and the cinematographed versions of AZT

“…The experimental article included in this number is perhaps a bet that sponges, which are like a gold mine for bioactive molecules, can recur this achievement, and house other relevant antiviral compounds, as side effects and acquired resistance is still a prominent bottleneck of many chemotherapy schemes, rather it is against cancer or infective diseases (9). As for Woodroof, well, he was too performing his kind of search for a better AIDS treatment, some 30 years earlier.…”