Data Sharing Enables Mud-Derived Polyanions to Stop HIV Replication
Researchers spend so much time keeping their workspace clean that the thought of willingly introducing mud into the lab is enough to cause skipped heartbeats. But what if molecules derived from mud behaved as polyanions that were cell culture compatible? If you’re a bench biologist, humic polyanions may be a vague or foreign concept—but if they were identified as a possible HIV treatment, ears would perk right up.
A new collaborative study published in the Royal Society of Chemistry journal shows that humic polyanions (PAs) will soon be a valuable component of prophylactic and therapeutic HIV treatment strategies.1 The new research examines an innovative new method for generating these PAs from mud-based humic acids. This enables the PAs to block HIV replication, with potential applications elsewhere in virology. Utilizing mud to derive polyanions for use against HIV, however, requires an extensive amount of data tracking and stochastic calculation. This, in turn, requires powerful, cutting-edge software to execute.
How Could Mud Yield An HIV Inhibitor?
For those biologists who may need a quick refresher on the finer points of polyanionic chemistry, polyanions are polyelectrolytes which2:
- Are charged
- Are water soluble
- Are viscous
- Easily polymerize
- Are biocompatible
Because of these traits, polyanions are ideal for use as stabilizers in medical gelatins, but don’t appear to be useful as therapeutics themselves—or so those unfamiliar with them might think. As it turns out, PAs have engaged in confirmed anti-HIV activity for decades.3 Due to their biochemical mechanism of action against viral envelopes, there’s also some research which suggests that PAs are useful against various viruses.4 It seems PAs may be a yet-unexploited treasure trove of future therapeutics.
Initial Problems with PAs: Infectivity and Sourcing Issues
PAs, however, are not a perfect solution. Not all polyanions are created equal, and some can even increase infectivity of HIV.5 It goes without saying that this is a serious problem, but it also means that each new PA will have to be subjected to infectivity amplification testing before it can get anywhere near a clinic. The potential for increased infectivity also increases the need for intense quality control during the isolation and production processes.
Sourcing PAs presents yet another problem. As the authors of the research note, “Still, controllable synthesis of polymers and dendrimers with tailored anti-HIV properties remains a laborious multi-step procedure.” Aside from the sheer difficulty of a complex isolation and synthesis operation, any PAs destined for cell culture use need to be purified and uniform—a difficult state to achieve due to their source material. Most biologists will groan at the thought of how many hours it would take to run the mass spectrometry required for purity confirmation and molecular characterization.
Exploring New Options
In fact, such difficulties inspired researchers to start exploring PAs which were mostly naturally synthesized and were uniformly HIV-inhibiting, yielding the new study. In particular, the study describes a PA subgroup dubbed carboxylated PAs. These PAs are derived from humic acid, which reproduces abiotically and is abundant in mud, soil, and groundwater. Recent advances in humic acid biochemistry have perfected the derivation of humic PAs from mud, and yielded enough material for researchers to thoroughly examine and experiment with.6
The combination of increased efficacy and easy access made the humic acids a perfect platform which researchers could then use to tweak and develop their therapeutic.7 Luckily for the bench scientists out there, the methodology used in the new research leans on mass spectrometry methods which unify isolation and quality control—a small consolation in a long process.
Flinging Mud At HIV
Once researchers had a sufficient source of PAs, they began analyzing their structures and testing them against the regions of HIV responsible for infection. With the help of abundant data mapping and molecular space visualization, the researchers were able to identify three PAs which electrostatically interacted with the part of the HIV viral capsule known to be essential for infection.8 The researchers found that their three PAs could stop infection of human cells when in contact with HIV.
Given that PAs are ideal for incorporation into medical gelatins, it’s easy to envision a PA-based prophylactic gel or therapeutic adjunct. Astute readers will point out that a gel-based PA therapy wouldn’t be curative, but the authors of the study have a response ready. As noted by the researchers, the veritable arsenal of HIV therapeutics can always make use of an additional tool to provide an edge in specific contexts or as a way of avoiding drug resistance.
There are quite a few steps needed to move from mud to viral replication inhibition that would be cell culture compatible, though. When experimenting with PAs, researchers are responsible for:
- Sourcing humic acid precursors from mud
- Fractionating the precursors uniformly with ion cyclotron resonance mass spectrometry9
- Confirming fractionation via functional assays
- Determine the molecular composition of the fractionated PAs
- Testing the produced PAs against viral disease models
- Determine structure-activity relationships of the PAs which inhibited viral reproduction
- Determine whether the PAs are cytotoxic
- Determine method of delivery for effective PAs
Each of these steps involves a separate set of data that needs to be tracked, analyzed, shared, and stored. What’s more, experiment plans, protocols, instrumentation booking, and personnel will have to work in tandem to execute the process successfully. The minor variations in each step’s data from run to run need to be specifically identified to ensure the next steps proceed smoothly. In order to keep track of all this data effectively, an excellent information technology platform is necessary for laboratories experimenting with PAs in virological applications.
BIOVIA’s Designed to Cure is a laboratory management and data sharing software platform that can unite the extensive pipeline required to develop PA-based viral therapies derived from humic acids. Designed to Cure can massively simplify PA drug development by allowing you to manage all experimental data under one roof. Contact us today to find out how BIOVIA can help you get the most out of the latest polyanionic research and move toward a cure to HIV.
- “Supramolecular Combinations Of Humic Polyanions As Potent Microbicides With Polymodal Anti-HIV Activities.” November 2016, http://pubs.rsc.org/-/content/articlehtml/2017/nj/c6nj00960c ↩
- “Glossary of Basic Terms In Polymer Science (IUPAC Recommendations 1996).” 1996, https://www.degruyter.com/view/j/pac.1996.68.issue-12/pac199668122287/pac199668122287.xml ↩
- “Dextran Sulfate Suppression Of Viruses In the HIV Family: Inhibition Of Virion Binding To CD4+ Cells.” 1988, http://chemport.cas.org/cgi-bin/sdcgi?APP=ftslink&action=reflink&origin=rsc&version=1.0&coi=1:CAS:528:DyaL1cXkt1Shsr0%3D&md5=80bc68e2b2c3e4a0be94c8b3890e68cd ↩
- “Polyanion Inhibitors Of HIV and Other Viruses. 7. Polyanionic Compounds and Polyzwitterionic Compounds Derived From Cyclodextrins As Inhibitors of HIV Transmission.” 1998, http://pubs.acs.org/doi/abs/10.1021/jm970661f ↩
- “The Rise And Fall Of Polyanionic Inhibitors Of The Human Immunodeficiency Virus Type 1.” 2011, http://chemport.cas.org/cgi-bin/sdcgi?APP=ftslink&action=reflink&origin=rsc&version=1.0&coi=1:CAS:528:DC%2BC3MXmvFSksbY%3D&md5=0b9239e8a83f6c755a5bc0b13cee022c ↩
- “Basis Of A Humeomics Science: Chemical Fractionation And Molecular Characterization Of Humic Biosuprastructures.” April 2011, https://www.ncbi.nlm.nih.gov/pubmed/?term=21361272%5Buid%5D ↩
- “Inhibition of HIV-1 In Cell Culture By Synthetic Humate Analogues Derived From Hydroquinone: Mechanism Of Inhibition.” April 1996, https://www.ncbi.nlm.nih.gov/pubmed/?term=8610466%5Buid%5D ↩
- “Mechanism Of Inhibitory Effect Of Dextran Sulfate And Heparin On Replication Of Human Immunodeficiency Virus In Vitro.” August 1998, http://www.pnas.org/content/85/16/6132 ↩
- “High-Field NMR Spectroscopy And FTICR Mass Spectrometry: Powerful Discovery Tools For the Molecular Level Characterization Of Marine Dissolved Organic Matter.” 2013, http://chemport.cas.org/cgi-bin/sdcgi?APP=ftslink&action=reflink&origin=rsc&version=1.0&coi=1:CAS:528:DC%2BC2cXltlCmtbk%3D&md5=6c561c974e605c115e2293d13d4852c9 ↩