New drug could cure nearly any viral infection

Researchers at MIT’s Lincoln Lab have developed technology that may potentialy cure the common cold, influenza and other ailments.

Anne Trafton, MIT News Office

Publication Date: August 10, 2011

The method works on all viruses that produce dsRNA such as the common yearly viruses, the cold, flu and influenza. Some do not produce dsRNA and latent viruses, probably the cause of many cancers, do not produce dsRNA.

Most bacterial infections can be treated with antibiotics such as penicillin, discovered decades ago. However, such drugs are useless against viral infections, including influenza, the common cold, and deadly hemorrhagic fevers such as Ebola.

Now, in a development that could transform how viral infections are treated, a team of researchers at MIT’s Lincoln Laboratory has designed a drug that can identify cells that have been infected by any type of virus, then kill those cells to terminate the infection.

In a paper published July 27 in the journal PLoS One, the researchers tested their drug against 15 viruses, and found it was effective against all of them — including rhinoviruses that cause the common cold, H1N1 influenza, a stomach virus, a polio virus, dengue fever and several other types of hemorrhagic fever.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022572

The drug works by targeting a type of RNA produced only in cells that have been infected by viruses. “In theory, it should work against all viruses,” says Todd Rider, a senior staff scientist in Lincoln Laboratory’s Chemical, Biological, and Nanoscale Technologies Group who invented the new technology.

Because the technology is so broad-spectrum, it could potentially also be used to combat outbreaks of new viruses, such as the 2003 SARS (severe acute respiratory syndrome) outbreak, Rider says.

Other members of the research team are Lincoln Lab staff members Scott Wick, Christina Zook, Tara Boettcher, Jennifer Pancoast and Benjamin Zusman.

Few antivirals available

Rider had the idea to try developing a broad-spectrum antiviral therapy about 11 years ago, after inventing CANARY (Cellular Analysis and Notification of Antigen Risks and Yields), a biosensor that can rapidly identify pathogens. “If you detect a pathogenic bacterium in the environment, there is probably an antibiotic that could be used to treat someone exposed to that, but I realized there are very few treatments out there for viruses,” he says.

There are a handful of drugs that combat specific viruses, such as the protease inhibitors used to control HIV infection, but these are relatively few in number and susceptible to viral resistance.

Rider drew inspiration for his therapeutic agents, dubbed DRACOs (Double-stranded RNA Activated Caspase Oligomerizers), from living cells’ own defense systems.

When viruses infect a cell, they take over its cellular machinery for their own purpose — that is, creating more copies of the virus. During this process, the viruses create long strings of double-stranded RNA (dsRNA), which is not found in human or other animal cells.

As part of their natural defenses against viral infection, human cells have proteins that latch onto dsRNA, setting off a cascade of reactions that prevents the virus from replicating itself. However, many viruses can outsmart that system by blocking one of the steps further down the cascade.

Rider had the idea to combine a dsRNA-binding protein with another protein that induces cells to undergo apoptosis (programmed cell suicide) — launched, for example, when a cell determines it is en route to becoming cancerous. Therefore, when one end of the DRACO binds to dsRNA, it signals the other end of the DRACO to initiate cell suicide.

Combining those two elements is a “great idea” and a very novel approach, says Karla Kirkegaard, professor of microbiology and immunology at Stanford University. “Viruses are pretty good at developing resistance to things we try against them, but in this case, it’s hard to think of a simple pathway to drug resistance,” she says.

Each DRACO also includes a “delivery tag,” taken from naturally occurring proteins, that allows it to cross cell membranes and enter any human or animal cell. However, if no dsRNA is present, DRACO leaves the cell unharmed.

Most of the tests reported in this study were done in human and animal cells cultured in the lab, but the researchers also tested DRACO in mice infected with the H1N1 influenza virus. When mice were treated with DRACO, they were completely cured of the infection. The tests also showed that DRACO itself is not toxic to mice.

The researchers are now testing DRACO against more viruses in mice and beginning to get promising results. Rider says he hopes to license the technology for trials in larger animals and for eventual human clinical trials.

This work is funded by a grant from the National Institute of Allergy and Infectious Diseases and the New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, with previous funding from the Defense Advanced Research Projects Agency, Defense Threat Reduction Agency, and Director of Defense Research & Engineering (now the Assistant Secretary of Defense for Research and Engineering).

Meet Todd Rider, Inventor of DRACO

Todd Rider, a biomedical engineer at MIT, Double-stranded RNA Activated Caspase Oligomerizer (DRACO).

Take me back to when you first discovered DRACOs. Did you immediately see their potential?

Because there were so few existing antiviral therapeutics, and those tended to be specific just for individual viruses or even just particular strains of individual viruses, I was motivated to develop new antiviral therapeutics that would be effective against a very broad spectrum of viruses. Rather than trying to invent something from scratch, I decided to borrow from what nature has already invented. Our cells have natural ways of detecting viral double-stranded RNA, and natural ways of triggering suicide in certain cells. I invented DRACO to combine those two natural systems and kill virus-infected cells. Just as the development of antibiotics completely revolutionized the treatment and prevention of bacterial infections in the mid-20th century, I believe that DRACO has the potential to completely revolutionize the treatment and prevention of viral infections in the 21st century.

You might think that a potential cure for all viruses would somehow generate sufficient interest and funding. Why hasn’t this happened?

Modest amounts of funding from the National Institutes of Health have enabled the previous proof-of-concept experiments in cells and mice, but that funding grant is now over. Major pharmaceutical companies have the resources and expertise to carry new drugs like DRACO through the manufacturing scale-up, large-scale animal trials, and human trials required for FDA approval. However, before committing any of their own money, those companies want to see that DRACOs have already been shown to be effective against major clinically relevant viruses (such as members of the herpesvirus family), not just the proof-of-concept viruses (such as rhinovirus) that were previously funded by NIH. Thus the Valley of Death is the financial and experimental gap between the previously funded NIH proof-of-concept experiments and the threshold for convincing major pharmaceutical companies to advance DRACOs toward human trials.

It seems as though DRACOs aren’t a silver bullet — separate therapies would have to be developed and tested individually, each at great cost.

In theory, one DRACO design should be effective against a very broad spectrum of viruses, and effective in a wide range of people. Starting from our initial proof-of-concept work, it may take some experimental optimization to find that best DRACO design.

What do you imagine a DRACO-based treatment would actually look like, if it were developed?

We have demonstrated that the initial version of DRACO can be successfully administered to mice as an injection or via inhalation. My ultimate goal is to develop DRACO in a pill form, but first I have to teach the mice how to swallow pills.

Do you believe the goal of curing all viral disease through DRACOs is attainable?

If we can successfully demonstrate and optimize DRACOs against clinically relevant viruses in cells, we believe those results should persuade pharmaceutical companies to carry DRACOs through large-scale animal trials and hopefully into human trials. The timeline depends on funding levels (including how much funding pharmaceutical companies are willing to commit later) and whether any unforeseen scientific difficulties arise in the experiments. However, if everything goes well, we hope that DRACO could enter human trials.

Broad-Spectrum Antiviral Strategies

Current antiviral drugs cover only a few of the hundreds of human viruses.

Over 200 viruses are known to cause disease in humans, yet currently approved antiviral drugs are available to treat only about 10 of these viral infections. - Preparing for the next viral threat with broad-spectrum antivirals

To “cover all viruses,” research focuses on broad-spectrum agents and combinations. One key example is DRACO (dsRNA-Activated Caspase Oligomerizer) – a fusion protein that binds any viral double-stranded RNA and triggers apoptosis in infected cells. Because most actively replicating viruses (RNA or DNA viruses during transcription) produce dsRNA intermediates, DRACO kills cells infected by viruses like influenza, dengue, arenaviruses, etc., without harming healthy cells. In fact, DRACO killed at least 15 different viruses in cell culture (flaviviruses, arenaviruses, bunyaviruses, H1N1 influenza) and protected mice from lethal influenza. In principle then, DRACO-like drugs could cover all viruses that generate any dsRNA. However, truly latent infections (e.g. herpesviruses, HIV provirus) produce no viral RNA (and hence no dsRNA) in their dormant state, so DRACO would not trigger apoptosis in those cases.

For example, Ebola virus is an enveloped filovirus with surface glycans. Novel synthetic carbohydrate receptor drugs bind viral surface sugars to block entry and have inhibited six unrelated viruses (Ebola, Nipah, Marburg, SARS-CoV-1/2) in cell culture and protected mice.

A new antiviral blocks 6 deadly viruses in mice but faces a long road ahead

Such approaches – along with DRACO and others – aim to treat multiple virus families with one agent.

Besides DRACO, several broad-spectrum antivirals are in development or use:

  1. Nucleoside Analogues (RNA Polymerase Inhibitors): These target viral replication enzymes shared by many RNA viruses. Examples include remdesivir and molnupiravir (RdRp inhibitors approved for SARS-CoV-2) and favipiravir (approved in Japan for influenza). The classic broad-spectrum drug ribavirin inhibits both RNA and DNA synthesis. In practice, ribavirin is used against RSV and HCV, and favipiravir against influenza. These drugs will hit most RNA viruses (including those DRACO covers) as well as some DNA viruses (e.g. HBV).
  2. Host-Directed Metabolic Inhibitors: Some approved drugs target host cell pathways essential for many viruses. For example, the antidiabetic biguanides metformin/phenformin activate innate immunity (AMPK-IFN pathways) and have shown antiviral effects in animals (metformin reduced influenza and dengue severity in mice; phenformin cut SARS-CoV-2 and dengue replication in cells and hamster). Other metabolic targets include atpenin A5 (a mitochondrial inhibitor) which also reduced diverse virus replication in vitro. These drugs work against multiple virus families because many viruses co‑opt similar host metabolism.
  3. Entry/Fusion Inhibitors: Broad entry blockers include agents that bind viral envelopes or host receptors. The dye LJ001 (a photosensitizer) irreversibly damages viral lipid envelopes, blocking entry of enveloped viruses (poxviruses, filoviruses, arenaviruses, influenza, etc.) in vitro. Similarly, arbidol (umifenovir, used in Russia for flu) acts on viral membrane fusion and has broad anti-influenza and coronavirus activity. Newer approaches mimic this idea: e.g. synthetic carbohydrate receptor molecules bind conserved N-glycan sites on virus surfaces (as in Ebola and SARS-CoV) to prevent attachment. In mice, one such compound enabled 90% survival after SARS-CoV-2 infection. These entry inhibitors add coverage for enveloped viruses (and would complement DRACO).
  4. Nuclear Export and Budding Inhibitors: Many RNA viruses export nucleocapsids or use the ESCRT pathway. The exportin-1 inhibitor verdinexor/KPT-335 blocked multiple influenza strains in cells and protected mice, and also inhibits some DNA viruses (e.g. HSV). Proteins like TSG101 (ESCRT-I) are essential for budding; compounds like FGI-104 and others targeting TSG101 block Ebola, influenza, HIV and HSV budding (in mice). These host-targeted agents act on a common step of enveloped virus life cycles, potentially covering any enveloped virus (especially if combined).
  5. Broad-Acting Approved Drugs: Several known drugs show multi-virus activity. For example, nitazoxanide (an antiparasitic) inhibits replication of diverse RNA and DNA viruses (influenza, dengue, HIV, HBV, JEV, even HSV), likely by disrupting viral protein maturation. Nitazoxanide is FDA-approved and in trials for influenza/COVID-19. Likewise, broad-spectrum antibiotics (e.g. azithromycin) and immunomodulators (e.g. IFN-α) have activity against multiple viruses, though resistance and toxicity limit use.
  6. Anti-Latency Strategies: No drug directly “kills” truly latent viruses, but strategies are being explored. The “shock-and-kill” approach uses epigenetic drugs to reactivate latent virus; for example, selective HDAC inhibitors (e.g. BRD3308 targeting HDAC3) can induce HIV expression from latency. Analogous approaches are studied for herpesviruses (e.g. arginine-butyrate or other HDAC inhibitors can wake latent HSV or EBV, followed by antiviral treatment). Gene-editing methods (CRISPR/Cas systems) are being developed to excise latent proviruses (HIV, HBV, HSV, etc.) though these are experimental. Immune therapies (e.g. broadly reactive antiviral T cells) can help control latent virus reactivation (as in transplant patients). In short, latent infections would require reactivation + clearance or gene therapies rather than conventional antivirals.

In sum, a minimal “pan-viral” arsenal would combine drugs from several classes. For example, DRACO (or similar dsRNA-triggered therapeutics) covers almost all replicating viruses; broad polymerase inhibitors (remdesivir, favipiravir, ribavirin) cover most RNA viruses; entry/fusion blockers (e.g. carbohydrate-receptor analogs) could stop any enveloped virus; host-targeted agents (e.g. verdinexor, phenformin) add redundancy across families; and epigenetic or gene therapies aim to purge latent reservoirs.

The table below summarizes key approaches and examples (approved drugs or candidates) covering different virus categories. Combining just a few complementary mechanisms could in principle provide effective treatment against all viruses.



Virus category / scenario                                 Broad-spectrum agent(s) or approach                        Notes and status (examples)                                            
 
 
 
**Viruses with dsRNA (most replicating RNA/DNA viruses)** DRACO (dsRNA-activated apoptosis)                          Experimental; killed ≥15 virus types in cells, protected mice          
Polymerase inhibitors (remdesivir, favipiravir, ribavirin) Approved or in trials; active vs broad RNA viruses (also some DNA/HBV) 
**Enveloped viruses (entry inhibitors)**                  LJ001/JL122 (envelope lipid oxidizer)                      Research; blocks fusion of many enveloped viruses in vitro             
Synthetic glycan-binding drugs (e.g. “SCR” compounds)      In development; blocked Ebola/Nipah/SARS etc. in cells and mice        
Arbidol (umifenovir)                                       Approved (Russia); broad activity vs influenza, some coronaviruses     
**General host-targeting antivirals**                     Verdinexor/KPT-335 (XPO1 inhibitor)                        Preclinical; blocked influenza and other viruses in animals            
Phenformin (biguanide)                                     Repurposed diabetes drug; inhibited SARS-CoV-2 and dengue in models    
Nitazoxanide                                               Approved (antiprotozoal); broad antiviral activity in vitro and trials 
**DNA viruses**                                           Cidofovir/Valacyclovir (nucleoside analogs)                Approved; cover herpesviruses, CMV, adenovirus (some cross-coverage)   
Cidofovir prodrug NPP-669                                  Preclinical; potent vs CMV, adenovirus in animals                      
**Latent/chronic infections**                             HDAC inhibitors (e.g. BRD3308)                             Research; reactivates latent HIV (shock-and-kill strategy)             
Adoptive antiviral T cells / immune therapy                Clinical; used post-transplant to control EBV/CMV reactivation         
CRISPR/Cas gene-editing (experimental)                     In development; could excise proviral genomes (HIV, HBV, herpes)       
**Others / adjuncts**                                     Interferons (IFN-α/β) and immune modulators                Approved; broad but limited by toxicity and viral evasion              
Combination immunomodulation (e.g. mRNA-induced ISG15)     Experimental mRNA therapies boosting host defenses

87.5% Broad Spectrum AntiViral Across 3 Methods

Interventions: DRACO + broad polymerase/replication inhibitor class + latency-targeting elimination strategy (3 interventions).

Coverage achieved (conservative mapping of 24 common human virus families): 21/24 → 87.5% covered.

Not covered (3 families, 12.5%): Papillomaviridae (HPV), Parvoviridae (B19), Anelloviridae (TTV). For these, practical responses are vaccines, local therapy/IVIG, or no therapy required respectively; future gene-editing could close gaps.

  1. DRACO (broad dsRNA-triggered apoptosis). DRACO status: DRACO is experimental (proof-of-concept in cells & mice). I treat it as a valid candidate broad-spectrum agent against viruses that produce accessible long dsRNA during replication. Strengths: Directly kills infected cells only when viral dsRNA is present → broad across viruses that produce long dsRNA replication intermediates (many RNA viruses, some DNA viruses during transcription). Very broad, rapid antiviral action. Weaknesses: Experimental; some viruses hide dsRNA or express dsRNA-sequestering proteins (poxviruses, coronaviruses sequester in DMVs) that reduce DRACO accessibility.
  2. Broad polymerase/replication inhibitor class. “Polymerase inhibitor” role: I use the phrase to mean a broadly-acting nucleoside/nucleotide analog strategy (examples: ribavirin-type broad inhibitors, remdesivir/molnupiravir classes for RdRp; separate approved drugs exist for DNA viruses — e.g., cidofovir/acyclovir class). This entry stands for the class of polymerase/replication inhibitors that can be applied (one or more clinical agents belonging to the class may be required in practice). Strengths: Targets viral replication machinery across many virus families (RdRp for RNA viruses; DNA polymerase inhibitors for DNA viruses). This class fills DRACO blind spots (viruses that hide dsRNA but still require polymerase activity). Several approved examples already exist (and more in trials). Weaknesses: Different families often require different specific drugs (a single small-molecule rarely works equally well across all families), toxicity and resistance are concerns; in the real world you’d select the best polymerase agent for the virus family.
  3. Latency-targeting elimination strategy. “Latency-targeting” strategy: includes “shock-and-kill” epigenetic latency reversal (HDAC/other modulators) + immune clearance (adoptive T cells, therapeutic vaccines) and/or gene-editing strategies (CRISPR) aimed at eliminating provirus/cccDNA reservoirs. This is treated as one combined strategy for our minimal set. Strengths: Required to cure or eliminate latent/persistent infections (HIV provirus, herpesvirus latency, HBV cccDNA, polyomaviruses). Approaches include latency reversal (HDAC/other epigenetic drugs) + immune clearance, adoptive T cells, therapeutic vaccines, and experimental gene-editing (CRISPR/Cas) to excise provirus. Weaknesses: Mostly experimental; safety and off-target risks exist; combination with immune therapies likely necessary.

The remaining gaps (the uncovered families) and practical solutions

  1. Papillomaviridae (HPV) — Not covered by the three interventions. Reason: HPV establishes persistent infection in basal epithelial layers, often with limited systemic replication that generates the dsRNA signals DRACO requires; systemic polymerase drugs are not clinically effective; latency reversal/gene editing for HPV is still experimental. Practical solutions: (a) prophylactic HPV vaccination (prevention). (b) local ablative/immune therapies for established lesions. © experimental CRISPR strategies to excise HPV episomes — research underway. Because HPV control is already achieved very effectively by vaccination and local therapy, this gap is acceptable in many public-health strategies.
  2. Parvoviridae (Parvovirus B19) — Not covered. Reason: small ssDNA virus with limited replication intermediates amenable to DRACO; few effective systemic antivirals exist; disease often supportive care or IVIG for severe cases (e.g., aplastic crisis). Practical solutions: IVIG for severe disease; vaccine research exists but no widely used vaccine; gene-editing approaches are theoretically possible but not practical now.
  3. Anelloviridae (Torque teno virus) — Not covered. Reason: ubiquitous/usually asymptomatic; clinical significance limited; no standard antivirals required. Practical solutions: none usually required; research if pathogenic role established.

87.5% Oral Broad Spectrum AntiViral Polypill

The current proposal suggests a 4 agent cocktail of Galidesivir, Brincidofovir, Nitazoxanide, Tamoxifen, and Lamivudine.

  

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