The Spirocyclic Imine from a Marine Benthic Dinoflagellate, Portimine, Is a Potent Anti-Human Immunodeficiency Virus Type 1 Therapeutic Lead Compound

Abstract

In this study, we aimed to find chemicals from lower sea animals with defensive effects against human immunodeficiency virus type 1 (HIV-1). A library of marine natural products consisting of 80 compounds was screened for activity against HIV-1 infection using a luciferase-encoding HIV-1 vector. We identified five compounds that decreased luciferase activity in the vector-inoculated cells. In particular, portimine, isolated from the benthic dinoflagellate Vulcanodinium rugosum, exhibited significant anti-HIV-1 activity. Portimine inhibited viral infection with an 50% inhibitory concentration (IC50) value of 4.1 nM and had no cytotoxic effect on the host cells at concentrations less than 200 nM. Portimine also inhibited vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped HIV-1 vector infection. This result suggested that portimine mainly targeted HIV-1 Gag or Pol protein. To analyse which replication steps portimine affects, luciferase sequences were amplified by semi-quantitative PCR in total DNA. This analysis revealed that portimine inhibits HIV-1 vector infection before or at the reverse transcription step. Portimine has also been shown to have a direct effect on reverse transcriptase using an in vitro reverse transcriptase assay. Portimine efficiently inhibited HIV-1 replication and is a potent lead compound for developing novel therapeutic drugs against HIV-1-induced diseases.

Metabolities from Marine Sponges of the Genus Callyspongia: Occurrence, Biological Activity, and NMR Data

“…Furthermore, 2-Bromoaldisine ( 105) was evaluated as a potential compound for anti-HIV action, by inhibiting type 1 of this virus with an infection vector to 1/3 at 200 nM in a 96-well plate [117]. Compound 105 also inhibited MEK-1 reasonably [118], and GSK-3 (IC 50 > 41.2 µM), DYRK1A (IC 50 > 41.2 µM), and CK-1 significantly (IC 50 1.6 µM) [119].…”

Natural Products as Potential Antiviral Drugs: The Specific Case of Marine Biotoxins

“…Dinoflagellates are a unique class of unicellular planktonic microalgae [ 26 ] and a source of a wide variety of biotoxins which present a potential for human health, and unexpected applications as pharmacological drugs. Their potential uses in biotechnological fields and more specifically in the war against viruses have been reported [ 27 , 28 ]. Due to the molecular structure complexity of these marine biotoxins [ 26 ], their synthesis of an industrial scale is too expensive, time consuming and too difficult to implement.…”

The Anti-Viral Applications of Marine Resources for COVID-19 Treatment: An Overview

“…For example, the marine algae, Padina tetrastromatica has shown to have immune stimulatory, antioxidant and anti-HIV properties [ 17 ]. Similarly, portimine, a molecule from the dinoflagellate Vulcanodinium rugosum , has shown to have significant anti-HIV effects by directly inhibiting the reverse transcriptase enzyme [ 18 ]. Furthermore, rhamnan sulfates derived from marine Green Algae Monostroma nitidum have been shown to inhibit the replication of influenza virus [ 19 ].…”