Project 3

Project 3

Goal & Research Areas

Our overall objective is to develop a new class of direct acting-antivirals (DAAs) that can specifically target viral envelopes but not host cell membranes using our novel amphipathic, α-helical (AH) Lipid Envelope Antiviral Disruption (LEAD) peptides and peptoids (sequence-specific N-substituted glycine oligomers). Therapeutics that can specifically target enveloped viruses have the potential to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a wide variety of RNA viruses of pandemic potential. One promising target is the lipid membrane coating that surrounds enveloped viruses, as membrane disruption can abrogate viral infectivity. This team’s investigators have developed a new class of AH peptides, and another new type of self-assembling amphipathic peptoids, that selectively form pores in high-curvature membranes such as membrane-enveloped virus particles (<160 nm diameter) but do not form pores in low-curvature membranes such as those of mammalian cells. Once a critical density of pores forms in the viral membrane, pore-induced membrane lysis occurs, leading to loss of viral infectivity.

We seek to advance the development of a promising lead molecule by: 1) further characterizing the biophysical properties of LEAD peptides and peptoids responsible for their antiviral activity against enveloped viruses; 2) optimizing in vivo pharmacokinetics (PK) of LEAD peptides and peptoids for subcutaneous and inhalation delivery suitable for outpatient administration; 3) evaluating antiviral efficacy of the optimized LEAD peptides and peptoids in mouse models of DENV, ZIKV, and SARS-CoV-2; and 4) nominating a top-performing LEAD peptide/peptoid for IND-enabling studies by collaborating with Project 6 on mechanisms of potential resistance to our top performing molecules, conducting synergy studies with other available DAAs including ones developed in SyneRx, and beginning initial assessments of in vitro ADME and in vivo non-GLP rat toxicity. Successful completion of our aims will yield an exciting novel class of DAAs that can specifically target viral envelopes for use alone, or in combination with other DAAs, to combat SARS-CoV-2 and other infections caused by membrane-enveloped viruses with pandemic potential.

Core Leader & Team

Nam-Joon Cho

Nam-Joon Cho

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Shirit Einav, MD

Annelise Barron

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Shirit Einav, MD

Shirit Einav

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Wah Chiu

Wah Chiu

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NamjoonCho
Nam-Joon Cho Professor, Nanyang Technological University Loacation: Research Techno Plaza, 06-05, Singapore 637553

Originally from Seoul, South Korea, Dr. Cho is a graduate of the University of California, Berkeley and Stanford University. Dr. Cho earned his doctorate in Chemical Engineering at Stanford under the guidance of Professor Curtis W. Frank. During his graduate studies, Dr. Cho first gained an interest in research at the interface of molecular virology and biomaterials. The principal goal of his thesis work was to develop lab-on-a-chip technologies for analysis of viral protein interactions with lipid membranes. Dr. Cho then continued his postdoctoral training in Professor Jeffrey S. Glenn's group in the Division of Gastroenterology and Hepatology at the Stanford University School of Medicine. He applied these engineering technologies to combat the hepatitis C virus (HCV), which affects over 170 million people worldwide. His work has led to significant advances for treating HCV, including new drugs currently in preclinical or clinical trials.

In addition, Dr. Cho has pioneered a novel approach to liver tissue engineering that has provided improved methods to study liver disease.In addition to his leadership of the Translational Science Group, Dr. Cho is active in the NTU community and serves as Deputy Director of the Nanyang Institute of Technology in Health and Medicine (NITHM) as well as Director of NTU's Research Experience for Undergraduates (REU) summer program in collaboration with the Asian Research Network. He is also a Principal Investigator at the Singapore- MIT Alliance for Research and Technology (SMART) and a Visiting Associate Professor at the Stanford University School of Medicine.

Dr. Cho's passion for translational and regenerative medicine has been recognized by several prestigious international honors and awards from the American Liver Foundation, Beckman Foundation, and leading global universities and companies including Chalmers University of Technology and Roche Ltd. In 2011, Dr. Cho was named an NRF Fellow by the Singapore National Research Foundation, and was also appointed to a Nanyang Associate Professorship. Dr. Cho is also the Founder of infollutionZERO, a global nonprofit organization committed to building a green digital world for future generations by raising awareness of infollution (information + pollution) in digital space and promoting digital literacy.

AbdulRahimFerhan
Dr. Abdul Rahim Ferhan Nanyang Technological University, Singapore Deputy Director, Translational Research ViRx@Stanford for Vietnam

Dr. Edward Pham receives his MD and Ph.D in Microbiology & Immunology from Stanford University.

His research focus is on novel antiviral therapies for current and emerging viral infections and the relationship between chronic viral infection and cancer including liver cancer through studying how the innate and adaptive immune system are perturbed in chronic viral infection.

He has been recognized by many prestigious awards such as National Research Service Fellowship from NIH for MD/PhD, Gates Millenium Scholar, Howard Hughes Medical Institute, International Achievement Summit Delegate.

SoohuynPark
Dr. Soohuyn Park Nanyang Technological University Head of Medicinal Chemistry of Stanford

Dr. Mark Smith joined Stanford ChEM-H in May 2013 as the Head of the Medicinal Chemistry Knowledge Center. He graduated with a Ph.D. from the laboratory of Prof. Richard Stoodley at the University of Manchester Institute for Science and Technology (UMIST), where his research focused on the application of Lewis acid catalyzed hetero Diels-Alder reactions to the synthesis of novel disaccharide structures. In 2000, Dr.

Smith joined the research laboratory of Prof. David Crich at the University of Illinois at Chicago. Here his research focused on the generation of new reagents for the synthesis of beta-mannosides from thioglycosides. From 2002 to 2013, Dr. Smith worked as a medicinal chemist in Roche’s research facilities both in Palo Alto, CA and then Nutley, NJ, where he specialized in antiviral research.

JianLi
Dr. Jian Li Nanyang Technological University 10+ years of experience in Healthcare Management M.S from U.C.S.F

Wendy is the CEO of IMI.AI, a company that allow doctors to give medical advice to patients seamlessly. Wendy has a proven executive management track record with almost ten years of experience in the healthcare and business industry. Wendy was previously Co-founder/CEO of Med2lab, a startup focuses on innovating medical training. The system got adopted by Stanford School of Medicine.

Before that, she spent 5 years in the Management Team at Marin General Hospital, working closely with the CEO, Lee Domanico, as her mentor. Wendy also acts as the President and Founder of Apollo Care, a 501(c)3 nonprofit organization that provides free healthcare support to poor children oversea. She’s also an alumni of Y Combinator founder track, one of the top incubators in the world.

Wendy attended Graduate program from the University of California, San Francisco and a Bachelor Degree in Psychology from UMass Amherst.