New Broad-Spectrum AntiViral Agent Holds Promise

UCLA researchers released their report on a tiny molecule that could eliminate many of the world’s most dangerous viral diseases (see list below), revolutionize antiviral therapy, and change the course of medical history.

Dr. M. C. Wolf and associate researchers, of the Department of Microbiology, Immunology, and Molecular Genetics at the University of California at Los Angeles, published their breakthrough findings concerning the antiviral molecule they call ‘LJ001′.

Here’s why LJ001 is such an important find.

A virus is an inert object, unable to do any harm until it enters and commandeers the biomolecular functions of a living cell for its own purposes. Viruses come in two basic variations: enveloped, and non-enveloped.

‘Enveloped’ viruses are enclosed within a two-layer lipid membrane that assists in attaching the virus to a host cell—the first step to infecting the cell. After attachment, the viral envelope must fuse with the cell membrane before genetic material can enter the cell.

Once inside, a virus forces the infected cell to copy its genetic instructions and manufacture more viruses until the cell, filled beyond capacity with the new viruses, finally bursts and dies. Each of the millions of newly expelled viruses then seeks a nearby cell to host its own replication.

To date, researchers have only been able to develop antiviral agents, like Ribavirin, that interfere with replication of the virus after it has entered the cell. The main problem with this approach lies in finding an antiviral agent that blocks the replicating function of the viruses, without interfering with any essential mechanisms in healthy, uninfected cells.

Every existing antiviral agent causes an assortment of side effects due to its toxicity to normal cells. Treatment with those compounds involves striking a balance between disabling at least enough of the viral population to control its spread, and disrupting the function of too many healthy cells.

Although viruses generally favor infecting a specific type of cell, they will invade other types when their preferred supply runs low, or conditions in those cells threaten their ability to replicate. Consequently, antiviral treatment can involve administering a series of medicines, literally chasing the virus through the body.

Now comes the long-sought molecule, LJ001, with its special ability: It prevents enveloped viruses from fusing to cell membranes.

Blocking membrane fusion leaves the virus in a vulnerable position: outside of cells, where the body’s immune system can attack it. Viruses that can’t hide inside cells are also more accessible by antiviral agents that won’t need to interfere with cellular functions to be effective.

LJ001′s ability to prevent fusion means this compound will be effective against a wide range of viruses with lipid envelopes, which cause some of the deadliest diseases known. Here is a list of viruses the researchers believe LJ001 will prove to be effective against:

• Arenaviruses: Lassa Fever in Africa, and several varieties of hemorrhagic fever in South America.
• Bunyaviruses: Hantavirus; Crimean-Congo hemorrhagic fever; California encephalitis; Rift Valley fever; La Crosse encephalitis; and plant viral diseases like Tomato spotted wilt virus.
• Filoviruses: Marburg hemorrhagic fever and Ebola hemorrhagic fever.
• Flaviviruses: Kyasanur forest disease; Tick-borne encephalitis; Deer tick virus encephalitis; Powassan encephalitis; West Nile fever; Omsk hemorrhagic fever; Japanese encephalitis; Dengue fever; St. Louis encephalitis; Zika fever; Australian encephalitis; and Yellow fever.
• Human immunodeficiency virus 1
• Influenza A viruses: seasonal human flu, bird flu, swine flu, cat flu, dog flu, and horse flu.
• Paramyxoviruses: Hendravirus and Nipahvirus; Mumps virus; Human parainfluenza viruses 1, 2, 3 and 4; Simian (monkey) virus 5; Tioman virus; Menangle virus; some common cold viruses; Sendai virus; Human respiratory syncytial virus and Bovine respiratory syncytial virus; Avian pneumovirus; Tupaia paramyxovirus; Human metapneumovirus; Newcastle disease virus; Canine distemper virus; Phocine distemper virus; Rinderpest virus; Reste des Petitis Ruminants virus; Measles virus; and several others.
• Poxviruses: viral diseases that affect a wide range of animals, some of which can be transmitted to humans: vaccinia, cowpox,and smallpox; Swinepox, Sheeppox, Fowlpox viruses; Orf virus; Myxoma virus; Yaba monkey tumor virus; Molluscum contagiosum virus; Dolphin poxvirus; Gray kangaroo and Red kangaroo pox viruses; Muledeer pox virus; Marmoset pox virus; and many others.

In terms of potential harm to living cells from this biological agent, the scientists report that LJ001 is safe. In both test tube and animal studies, at concentrations high enough to inactivate the viruses, there were no signs of toxicity to the cells.

Even after exposure to LJ001 was discontinued, viruses remained unable to fuse to cell membranes. This fact indicates that an antiviral medication derived from LJ001 could be effective if administered over several days, instead of over numerous months, which is how antivirals are currently administered.

Through changing their preference for host cells, and developing resistance to antiviral agents, viruses are famous for their ability to adapt to adverse environmental circumstances. These qualities that make viruses so elusive during treatment come about through mutations occurring during viral replication.

Altered host cell preference, and resistance to antiviral compounds won’t be possible during treatment with LJ001. By inactivating the virus before it can enter a cell, LJ001 will avert such mutations. A virus that cannot replicate, cannot mutate.

In summary, by preventing fusion, LJ001 will prevent replication; the development of resistance; mutation; and the diseases listed above. The defenseless viruses will be like sitting ducks for destruction by the body’s immune system, which may be able to accomplish its mission without any additional antiviral therapy.

Discovering a safe and effective broad-spectrum antiviral like LJ001 is to biomedical science what putting a man on the moon was to aerospace engineering. Further research is underway on this minuscule molecule that holds tremendous promise for the health of all living creatures.

I predict that the discovery of LJ001 will turn out to be a historic moment for infectious disease medicine, and a turning point for humans in terms of morbidity and mortality.

And we thought eradicating smallpox was a momentous achievement…!

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Wolf MC, Freiberg AN, Zhang T, Akyol-Ataman Z, Grock A, Hong PW, Li J, Watson NF, Fang AQ, Aguilar HC, Porotto M, Honko AN, Damoiseaux R, Miller JP, Woodson SE, Chantasirivisal S, Fontanes V, Negrete OA, Krogstad P, Dasgupta A, Moscona A, Hensley LE, Whelan SP, Faull KF, Holbrook MR, Jung ME, Lee B. A broad-spectrum antiviral targeting entry of enveloped viruses. Proceedings of the National Academy of  Science, U S A.  2010 Feb 16;107(7):3157-62. Epub 2010 Jan 28.

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