May 28, 2020 – New COVID-19 related NSF grant: “Arresting the spread of SARS-CoV-2 on surfaces and in the air using engineered water nanostructures enriched with de novo designed neutralizing peptides”

Press Release, Boston MA, 5/28/2020 – The recent COVID-19 pandemic caused by SARS-CoV-2 has spotlighted the problem of transmission of infectious diseases. SARS-CoV-2 is transmitted to new hosts through both surface droplet (fomite) and aerosol droplet-nuclei transmission. Based on emerging data, this virus can survive in air for hours and on surfaces for days. Control of viral transmission remains a challenge, and all current intervention approaches, such as masks, frequent hand washing, and social distancing, are insufficient and detrimental, especially when people start returning to their working environments. In the current pandemic, the high numbers of asymptomatic cases and shortage of efficient facemasks are also driving the number of infections higher, necessitating the development of novel intervention approaches. Current methods for prevention of transmission of infectious diseases such as hand wash, air filtration, and use of chemical gases (e.g. hydrogen peroxide) have significant shortcomings and health risks. Therefore, there is an urgent, unmet need for new intervention technologies that can minimize the risk of infection, augmenting and perhaps transforming critical prevention efforts.  To this end, researchers at the Center for Nanotechnology and Nanotoxicology (HCNN) at the Harvard T. H. Chan School of Public Health submitted a grant proposal to study the application their recently developed Engineered Water NanoStructures platform as a means to inactivate the SARS-CoV-2 virus.  This proposal was accepted by the National Science Foundation (NSF) and will be funded for one year, starting July 1, 2020.

Nanotechnology and synthetic biology to the rescue: Researchers at HCNN recently developed a nanotechnology based antimicrobial method using Engineered Water NanoStructures (EWNS). EWNS are synthesized using a combined electrospray and ionization process of aqueous suspensions of antimicrobial active ingredients (AI). These EWNS have unique properties: They are highly mobile due to their nanoscale size, are electrically charged, which results in lifespan of hours in room conditions, and can carry both antimicrobial agents and reactive oxygen species (ROS) from ionization of water. These EWNS have been shown to interact and inactivate the Influenza H1N1 virus and other pathogens on surfaces and in air. Since SARS-CoV-2 is an enveloped virus, like Influenza H1N1, researchers at HCNN expect it to be highly susceptible to EWNS exposures on both surfaces and in the air.

Disulfide-rich peptides (DRPs) are an ideal platform for engineering neutralizing agents that can be incorporated into EWNS for environmental decontamination. DRPs are hyperthermostable and resist chemical denaturation, and   recently developed computational methods by the investigators will enable them to rationally design DRPs to bind neutralizing epitopes. Previous work by the group demonstrated this by engineering a DRP that neutralizes influenza by binding to its hemagglutinin protein. The work performed as a part of this new grant will adopt the same approach to design and produce neutralizing DRPs for SARS-CoV-2. Such DRPs will be incorporated in the EWNS chemical structure and used to inactivate the virus both in the air and on surfaces. The nano-virus interactions and efficacy of peptide-enriched EWNS to neutralize the virus will be assessed using state of the art biological methods.

The research to be carried out as a part of this newly awarded grant combines excellence in nano-science and synthetic biology. Novel computational methods will be used to design neutralizing DRPs de novo and functionalize them to bind the spike protein SARS-CoV-2 and block it from interacting with ACE2, its endogenous receptor. Such DRPs will be incorporated in a nanocarrier platform using engineered water nanostructures and efficiently delivered to inactivate the virus both in the air and on surfaces. Such a “game changing” approach, if successful, will revolutionize the way we intervene to minimize the risks of infection in our indoor micro-environmental settings.

Principal Investigator: Dr. Philip Demokritou. Co-PI, Christopher Bahl, Institute of Protein Innovation. Co-Is: Drs. Nachiket Vaze and Runze Huang