The Lingappas and their quest for anti-viral treatments

Wired magazine has a fascinating in-depth article on emerging approaches to prevent and treat viral infections. An interesting angle to it is the brother-sister duo Vishwanath and Jaisri Lingappa, whose approach could potentially lead to a cure for most viruses. Antibiotics had a profound effect on our lives, and have fundamentally transformed human society. When similar broad-spectrum treatments for viruses are found, they will save millions more lives. Check out the article for more.

The writer was interviewed on NPR the other day: http://www.wbur.org/npr/150003129/the-race-to-create-the-best-antiviral-drugs

charvaka wrote:The writer was interviewed on NPR the other day: http://www.wbur.org/npr/150003129/the-race-to-create-the-best-antiviral-drugs

I heard it on NPR yesterday on All things considered - evening edition (I think). Fascinating overview of virus, bacteria, and humans and various techniques being tried and tricked.

Thanks for posting this article. Finally a post on something I did my Phd on ..

Lingappa's approach sounds good. But from that to extrapolate it to finding a broad-spectrum anti-viral sounds like 'pie in the sky'. His company website says that they have found key host cell proteins required for viral capsid assembly for many viral families. These host cell proteins are different from one virus family to another. So targeting one with a small molecule will eliminate or restrict one viral family not the other one. So it can't be broad spectrum. Finding a single host protein used by all the disease causing viruses and hoping that targeting that protein wouldn't be detrimental to the host is a dream scenario for all virologists.

Second approach of using Polyethylene glycol (PEG) to modify interferon is not something new or groundbreaking. PEGs are mainly used to reduce immune response by the patient to a protein drug and they don't fundamentally change the properties of the protein per se but alter the pharmacokinetic profile of the drug. There are many protein drugs that are PEG-modified in the market currently.

I have to get to a meeting. .will post about the third approach shortly.

doofus_maximus wrote:Thanks for posting this article. Finally a post on something I did my Phd on ..

Lingappa's approach sounds good. But from that to extrapolate it to finding a broad-spectrum anti-viral sounds like 'pie in the sky'. His company website says that they have found key host cell proteins required for viral capsid assembly for many viral families. These host cell proteins are different from one virus family to another. So targeting one with a small molecule will eliminate or restrict one viral family not the other one. So it can't be broad spectrum. Finding a single host protein used by all the disease causing viruses and hoping that targeting that protein wouldn't be detrimental to the host is a dream scenario for all virologists.

Second approach of using Polyethylene glycol (PEG) to modify interferon is not something new or groundbreaking. PEGs are mainly used to reduce immune response by the patient to a protein drug and they don't fundamentally change the properties of the protein per se but alter the pharmacokinetic profile of the drug. There are many protein drugs that are PEG-modified in the market currently.

I have to get to a meeting. .will post about the third approach shortly.

Interesting... so if messing with single host protein won't prevent the replication of all viruses, is it possible to at least apply the core idea to all disease-causing virus families and find the appropriate host proteins to tweak? If that IS possible, then the lack of a broad-spectrum solution may not be a bad thing, because the broad-spectrum one would stop all viruses, regardless of whether they cause diseases or play other potentially beneficial roles.

Do post your comments on the third approach!

charvaka wrote:

Do post your comments on the third approach!

I am deeply, deeply hurt that you are not seeking my expert views on this third approach...

Marathadi-Saamiyaar wrote:

charvaka wrote:

Do post your comments on the third approach!

I am deeply, deeply hurt that you are not seeking my expert views on this third approach...

Ayyo, as the omni-expert, your views are sought on any and every topic by default.

Lingappa's approach: It is not that researchers haven't been trying to target host cell machinery/proteins to combat infectious viruses. For eg: HIV research focused and still focus on finding molecules which will inhibit HIV's entry into a host cell. Host cells have protein molecules on their surface that are called 'receptors', to which a virus binds and enters.

For HIV, there are two receptors, namely CD4 and chemokine receptor. Scientists have put in multiple decades-long work into finding a molecule which will disrupt HIV binding to these receptors, but to no avail.

Reasons being that 1)these receptors are very very essential for the normal functioning of the cell and 2) many viruses like HIV or Influenza constantly mutate and change their structure thereby rendering a inhibitor molecule essentially ineffective against the mutated virus.

Similar to viral entry into a cell, researchers have been studying and targeting other processes that occur during a viral lifecycle for which host cell proteins are essential. (viral dna/rna encapsidation, viral capsid assembly). Lingappa is targeting capsid assembly.

I quickly skimmed all the articles published by his group and his collaborators and have not found any host cell protein that is common for all viruses. In fact his methods haven't even identified any host cell protein specifically other than one protein in HIV capsid asembly. They have just found a bunch of promising molecules which inhibits viral capsid assembly for several different viruses.

Given that, it is pure hyperbole to say that there will be a broad-spectrum anti-viral from his work.

Caru, your concern about broad-spectrum anti viral destroying beneficial native viral ecology in humans is valid. But the fact is precious little is known about the viral ecology in our body and what benefits they provide us. So if I am developing a novel broad-spectrum anti-viral I wouldn't worry about that aspect too much.

Third Approach:
Of the three mentioned in the article, this is the most innovative and novel. There are some caveats to this approach as well. There is but one paper on this approach by the author. But it got lot of media attention which it deserves.

The paper describes in great detail about the ways the novel protein drug works. They showed some promise in early mice work. But it is a long way from here to the clinic.

The way this protein drug works is to identify a form of RNA (dsRNA) present only in virally infected host cells and trigger a response in those cells that tells the cells to commit cell-death (apoptosis). Main caveat to this approach is that viruses are very smart in a way to hide this form of RNA from the host detection mechanisms. If this protein drug can't detect these RNA forms, then it would be ineffective. But it seems to work in the preliminary work they have shown in the paper.

If I were a VC, I would fund the last approach.

Thanks for posting this.