Biological engineering company Ligandal, Inc. is applying its unique peptide-based delivery technologies to develop a prospective antidote and vaccine for SARS-CoV-2 (the novel coronavirus) to be formulated and developed in response to the worldwide pandemic. 

Ligandal's approach utilizes peptide scaffolds (think of them as nanorobots) that are designed with supercomputing and artificial intelligence (AI) to mimic the critical immune binding and responsive elements of the virus. Additionally, these peptide scaffolds can be designed to serve as rapid-response antidotes to an ongoing infection. 

The company's peptide-based technology is expected to aid in eliminating the virus from an already-infected host, while bolstering the immune response. In other words, the approach to creating vaccines and antidotes against SARS-CoV-2, whereby the damage of SARS-CoV-2 / COVID-19 is offset, is to eliminate the immune cloaking mechanisms of the virus and instill an ultra-specific immune response. This contrasts existing vaccine and therapeutic options which may not adequately form an immune response, and frequently treat symptomatic conditions without addressing the root cause of viral propagation and infection. 

"We are looking at medicine in a new way," stated Ligandal's CEO Andre Watson.  "Instead of treating symptoms or downstream effects, our approach is to reprogram the source of the problem, whether it be at the level of proteins, RNA or DNA. In other words, we can predictively model, synthesize and treat a variety of diseases at their source. This means that the normal way of treating diseases such as viruses and cancers, killing them, can be transformed to reprogramming and printing the body's own physiology to heal from within. 

"This changes all the assumptions, enabling a new way of thinking for treating disease and creating life enhancement. These same techniques can be used for rare monogenic diseases, complex multifactorial diseases, infectious diseases, regenerative medicine, immunotherapies, and beyond. This is because we are working at the atomic level, ranging from designing custom protein-mimetic peptides to building sophisticated nanoscale delivery systems for delivering DNA, RNA, CRISPR, and beyond." 

In the present instance, the company is reprogramming the viral binding elements of SARS-CoV-2 ("COVID") to no longer afford a "cloak" for this sophisticated immune-shielded virus.  It also offsets the need for alternative therapeutic solutions because the peptide scaffolds will expose the virus for the host's own immune system to learn and deal with. This approach is fully synthetic, which lends itself to rapid prototyping and personalized approaches for various viruses.  It can also scale-up on the order of days or weeks instead of years. 

"Ligandal's goal is to make lifecare available for all, and affordable for all," stated Eric Greenberg, member of Ligandal's board of directors. "Today's systems are not optimized for our current technology and understanding of the human genome. They weren't engineered from scratch with today's knowledge.  As I foreshadowed in 2003 in the Acumen Journal of Life Sciences, where I was Chairman and CEO, I warned the world of bio-warfare and asked if we were prepared.  Medicine must rethink traditional approaches if we are to rapidly respond to threats from new generations of pathogens, whether they crossed species or were bioengineered. It is our opinion that COVID is also a neurological virus.  We are seeing today how rapidly these pathogens can spread and impact both respiratory and neurological systems, putting entire communities at risk.  That's why Ligandal is aggressively pursuing treatment strategies that can rapidly adapt to any form of viral attack and/or infection." 

Immunity and Protection Challenges

Current approaches of developing vaccines and allopathic treatments may not provide adequate protection against this virus, given the virus' sophisticated immune cloaking mechanisms whereby the virus forms a coating in soluble ACE2, which is also present upon the cell membrane as a viral-entry mechanism. However, this soluble ACE2 is hypothesized to act as a shield against antibody binding sites on the virus' spike protein, which would effectively cloak the virus from adaptive immune recognition. 

This, coupled with the virus' other mechanisms for burying antibody immune-epitope sites, poses a significant problem in eliminating the virus from the body. Ligandal's peptide scaffolds are designed to be ultra-high-affinity, fully-synthetic constructs that can serve as competitive displacers to the viral entry mechanisms, as well as preventing ACE2 from forming its cloak around the virus. Furthermore, the scaffolds are designed to act as immune boosters, presenting precise antibody immuno-epitopes as well as T-cell receptor (TCR) immuno-epitopes against the key viral immunogenic sites. 

Considering how easily COVID is transmitted, Watson asserts, "Social isolation is the only scientifically valid policy for combatting infection.  Our research is showing that the virus survives in the air as a fine mist or aerosol, and readily infects people through the eyes and mucosa. This fine particulate matter is a mist and can remain active in the air for hours, depending on environmental factors and how many people are present. This means COVID is everywhere. So, before there is an antidote, society cannot be assured that they are safe from this existential threat. Further, simply refraining from handshakes, hugs and other physical contact isn't enough. Both social distancing and isolation are vital because it is the mist that sickens people. As a scientist, what I'm suggesting to policy makers that we consider social isolation combined with operating society as best we can while an antidote is developed. We do not think that we are the only solution to the COVID problem. I plead that the government of the United States of America vigorously pursues any and all antidotes for COVID by any parties, in the form of a Manhattan Project, to eradicate this threat to society."

Ligandal Research and Development in the Light of Current Pandemic

COVID has made possible a new way of thinking about medicine and healthcare, through creating atomically precise, genetically tailored, peptide and drug/gene delivery nanosystems for broad therapeutic, vaccine, and preventative medical purposes.

Ligandal CEO Watson wants mankind to explore and test the efficacy of these types of AI nanomaterial robotic curative approaches. Its new approach to curing the cause, versus treating the symptoms, is a potential breakthrough moment for medicine, made possible by the tragic coronavirus pandemic. 

Interested policy makers, genetic scientists and healthcare professionals can review Ligandal's prior work at www.ligandal.com. Please refer to "Rapid Simulation and Design of Synthetic Peptide Mini-Scaffold Vaccines for Novel Coronavirus (SARS-CoV-2) and Pandemic Preparedness." A video on the website explains the strategy for aligning a SWISSMODEL structure of SARS-CoV-2 (the novel coronavirus) to its binding site with Gibbs free energy plots of key interacting residues, as well as comparing to the Veesler Lab cryo-EM structures of the viral spike protein in open and closed conformations. Ligandal worked with Dr. Jinbo Xu, a professor at Toyota Technological Institute at Chicago and a Senior Fellow at the Computational Institute at the University of Chicago, to simulate its proprietary sequences in their final, folded conformations. 

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